Objective: To explore the relationship between tumor necrosis factor like weak inducer of apoptosis (TWEAK) gene and the pathogenesis of rheumatoid arthritis (RA) by detecting the DNA methylation level, mRNA expression level and serum protein concentration of TWEAK gene in peripheral blood. Methods: The MassARRAY method was used to detect the DNA methylation level of the TWEAK gene in the peripheral blood of 112 RA patients and 86 matched healthy volunteers. The real-time quantitative polymerase chain reaction method was used to detect the mRNA expression level of the TWEAK gene in the peripheral blood of the subjects. The enzyme-linked immunosorbent assay method was used to detect the serum TWEAK protein concentration of the subjects. The TWEAK gene DNA methylation level, mRNA expression level and serum protein concentration between the RA group and the healthy control group were compared, and the relationship between it and the degree of disease activity analyzed. Results: The overall DNA methylation level of TWEAK gene and the DNA methylation levels of CpG_11, CpG_17.18.19.20, CpG_40.41.42 site in the RA group were higher than those in the healthy control group (P=0.002, P=0.01, P=0.006, P=0.002, respectively). The DNA methylation level of CpG_55.56 site in the high disease activity group was higher than that in the medium and low disease activity group (P=0.041). The expression level of TWEAK gene mRNA in the peripheral blood of the RA group was lower than that of the healthy control group (P=0.023). The expression level of TWEAK gene mRNA in the high disease activity group was lower than that in the medium and low disease activity group (P=0.035). The serum TWEAK protein concentration of the RA group was not significantly different from that of the healthy control group (P=0.508), but it was positively correlated with the mRNA expression level (r=0.482, P<0.001). Conclusion: The TWEAK gene is closely related to the onset and progression of RA, and its hypermethylation state may be one of the epigenetic mechanisms regulating its low mRNA expression, and it can be used as one of the important indicators for clinical monitoring and evaluation of RA.

Objective: To detect the serum level of soluble chemokines CXCL9 and CXCL10 in patients with rheumatoid arthritis (RA), and to analyze their correlation with bone erosion, as well as the clinical significance in RA. Methods: In the study, 105 cases of RA patients, 90 osteoarthritis (OA) patients and 25 healthy controls in Peking University People’s Hospital were included. All the clinical information of the patients was collected, and the serum CXCL9 and CXCL10 levels of both patients and healthy controls were measured by enzyme-linked immune sorbent assay (ELISA). CXCL9 and CXCL10 levels among different groups were compared. The correlation between serum levels with clinical/laboratory parameters and the occurrence of bone erosion in RA were analyzed. Independent sample t test, Chi square test, Mann-Whitney U test, Spearman’s rank correlation and Logistic regression were used for statistical analysis. Results: The levels of CXCL9 and CXCL10 were significantly higher in the RA patients [250.02 (126.98, 484.29) ng/L, 108.43 (55.16, 197.17) ng/L] than in the OA patients [165.05 (75.89, 266.37) ng/L, 69.00 (33.25, 104.74) ng/L] and the health controls [79.47 (38.22, 140.63) ng/L, 55.44 (18.76, 95.86) ng/L] (all P<0.01). Spearman’s correlation analysis showed that the level of serum CXCL9 was positively correlated with swollen joints (SJC), rheumatoid factor (RF) and disease activity score 28 (DAS28) (r=0.302, 0.285, 0.289; P=0.009, 0.015, 0.013). The level of serum CXCL10 was positively correlated with tender joints (TJC), SJC, C-reactive protein (CRP), immunoglobulin (Ig) A, IgM, RF, anti-cyclic citrullinated peptide antibody (ACPA), and DAS28 (r=0.339, 0.402, 0.269, 0.266, 0.345, 0.570, 0.540, 0.364; P=0.010, 0.002, 0.043, 0.045, 0.009, <0.001, <0.001, 0.006). Serum CXCL9 and CXCL10 levels in the RA patients with bone erosion were extremely higher than those without bone erosion [306.84 (234.02, 460.55) ng/L vs. 149.90 (75.88, 257.72) ng/L, 153.74 (89.50, 209.59) ng/L vs. 54.53 (26.30, 83.69) ng/L, respectively] (all P<0.01). Logistic regression analysis showed that disease duration, DAS28 and serum level of CXCL9 were correlated with bone erosion in the RA patients (P<0.05). Conclusion: Serum levels of CXCL9 and CXCL10 were remarkably elevated in patients with RA, and correlated with disease activities and occurrence of bone erosion. Chemokines CXCL9 and CXCL10 might be involved in the pathogenesis and bone destruction in RA.

Objective: To investigate the clinical characteristics, risk factors and prognosis of ulcerative keratitis (UK) in patients with rheumatoid arthritis (RA). Methods: Sixteen patients with UK (the UK group) were screened among 4 773 RA patients hospitalized at Peking University People’s Hospital from January 2003 to May 2021, and 72 patients with RA without UK in the control group were selected by propensity score matching (PSM). The clinical features, laboratory data and medications between the two groups were collected and analyzed. Results: The average age of the patients with RA was 60 years at the time of the complication of UK. UK appeared on average in the 16th year of RA, with the majority of UK occurring in the 7th year of RA and beyond (14 cases), however, a minority of UK was the first symptom of RA (1 case). UK associated with RA manifested as simple marginal UK in 8 cases, marginal UK with perforation in 5 cases, marginal UK with uveitis in 2 cases and central UK with perforation in 1 case. The number of swollen joints was significantly higher in the UK group than in the control group [6.0(2.5,23.0) vs. 3.0(1.0, 9.8), Z=-2.047, P=0.041], and the proportion of secondary Sjögren syndrome (SS,37.5% vs. 6.9%, χ²=11.175, P=0.004) and interstitial lung disease (ILD, 37.5% vs. 8.3%, χ ²=9.456, P=0.008) were significantly higher in the RA patients with UK than the patients without UK. The uses of sulfasalazine (12.5% vs. 48.6%, χ ²=7.006, P=0.008), leflunomide (31.3% vs. 63.9%, χ ²=5.723, P=0.017) and gold salt(6.3% vs. 33.8%, χ ²=4.841, P=0.032)were significantly lower in the UK group than in the control group. However, there was no statistically significant comparison between the two groups for the 28-joint disease activity score-erythrocyte sedimentation rate (5.3±1.8 vs. 5.1±1.6, t=0.309, P=0.761). Logistic analysis showed the number of swollen joints (OR=1.148), secondary SS (OR=79.118), complicated with ILD (OR=6.596) and the use of sulfasalazine (OR=0.037) were independent relevant factors (P<0.05) for UK in RA patients. Conclusion: The number of swollen joints, secondary SS, complicated with ILD and the use of sulfasalazine are independent relevant factors for UK in patients with RA.

Objective: To investigate the agreement between clinical signs (tenderness and/or swelling) in ankles and feet joints and ultrasound findings in patients with rheumatoid arthritis (RA). Methods: RA patients with at least 1 tender and/or swollen joint in bilateral ankles and metatarsophalangeal (MTP) joints detected by physical examination were enrolled and underwent ultrasound examination by greyscale (GS) and power Doppler (PD) mode. The agreement between clinical signs and ultrasound-detected inflammation (joint effusion, synovitis, or tenosynovitis) was analyzed. Results: In the study, 113 consecutive RA patients were included, with mean age of (52.5±12.6) years, median duration of 60 (13, 129) months, mean disease activity score in 28 joints based on erythrocyte sedimentation rate [DAS28 (ESR)] of 5.1±1.7,mean disease activity score in 28 joints based on C reactive protein[DAS28 (CRP)]of 4.6±1.5. The tenderness and swelling was most commonly detected in ankles (52.7% and 31.9%, respectively), while GS (+) synovitis was most frequently detectable in MTP2 (34.1%), followed by ankles (32.7%) and MTP1 (27.9%),and PD (+) synovitis was most frequently detectable in MTP1 (14.2%), followed by ankles (12.4%) and MTP2 (10.6%). The prevalence of tenosynovitis was 41.1%, which mostly located in tibialis posterior tendon (22.1% of GS positive and 17.6% of PD positive). The highest prevalence of joint effusion was detected in ankles (9.7%), while that of bone erosion in MTP5 (19%). The overall concordance rate between positive clinical signs and ultrasound-determined joint inflammation was poor in the above joints (κ<0.2, P<0.05), in which swelling had the highest κ coefficient with ultrasound-determined joint inflammation in ankles (κ=0.225, P<0.05). Moreover, swelling had the highest κ coefficient with synovitis in ankles (κ=0.231, P<0.05).The concordance between tenosynovitis and signs in ankles was also poor (κ<0.20, P<0.05). There was no significant agreement between joint effusion and clinical signs (P>0.05). Conclusion: The overall concordance between clinical signs and inflammation on ultrasound was poor in ankles and feet joints. Tenderness and swelling was more common in ankles, while more lesions were detected by ultrasound at MTP joints. Ultrasound is useful in assessing the lesions besides physical examination in patients with RA.

Objective: To improve the understanding of the clinical characteristics of immunoglobulin G4-related disease (IgG4-RD) with central nervous system (CNS) involvement, so as to contribute to the early diagnosis and treatment. Methods: In this study, 10 patients with IgG4-RD with CNS involvement were selected. Clinical data including demographic features, clinical manifestations, organ involvement, laboratory findings, radiological results, pathology, treatments and outcomes were collected retrospectively. Results: Among the 10 IgG4-RD patients complicated with CNS involvement, 6 cases manifested as pituitary involvement and 4 cases manifested as dural involvement. Only 2 patients had nervous system involvement alone, while the left patients were complicated with other organ involvement besides nervous system. Half of the patients presented nervous system involvement as the initial manifestation, and the main symptoms of nervous system included polydipsia, polyuria, headache, decreased vision and so on. In the laboratory examination, the serum IgG4 level was increased in 9 cases (90.0%), and the total serum IgE was increased in 7 cases (87.5%). At the same time, their IgG, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were increased, while complement (C) 3 and C4 were decreased in some patients. Eight patients underwent tissue biopsies in different parts, the pathological examination showed a large number of lymphocyte and plasma cell infiltration, accompanied by fibrous tissue proliferation in part. All the patients were treated with glucocorticoids, and 8 cases (80%) were given immunosuppressants at the same time, and 3 cases were treated with rituximab when they expe-rienced disease relapse. As a result, 2 cases (20%) achieved complete remission (CR), and 8 cases (80%) achieved partial remission (PR). The median follow-up time was 13.5 months, and 4 cases relapsed. Conclusion: Pituitary and dura are common affected organs of IgG4-RD with CNS involvement. Most IgG4-RD patients with CNS involvement are combined with other organ involvement, but half of them presented nervous system involvement as the initial manifestation, and the symptoms are not typical. In order to make an early diagnosis, laboratory, imaging examination and tissue biopsy should be taken into consideration in combination if necessary.

Objective: To study the proportion of cervical spine instability in treatment-naive rheumatoid arthritis (RA) patients, to investigate the associated neck symptoms, and to analyze the clinical characteristics in treatment-naive RA patients and treated RA patients. Methods: RA patients who underwent cervical spine X-ray imaging from the Department of Rheumatology and Immunology of Peking University Third Hospital and Peking University Shenzhen Hospital from August 2015 to October 2019 and had clinical records of medication administration were included. Clinical and laboratory data including cervical symptoms and X-ray imaging data of cervical spine were collected. The constituent ratio of cervical spine instability in treatment-naive RA patients was statistically analyzed. The clinical data and laboratory data were analyzed by t-test, u-test and chi square to explore the clinical characteristics of the treatment-naive RA patients with cervical instability. Results: Of the 408 RA patients, 105 patients were treatment-naive. Of the 105 treatment-naive patients, 82.9% (87/105) were female, with an average age of (52±14) years, the median duration of the disease was 24 months, the shortest history was 2 weeks, and the longest history was 30 years. 28.6% (30/105) of the treatment-naive RA patients showed cervical spine instability. The prevalence of cervical instability was 13.6% in the treatment-naive RA patients with disease duration less than 24 months. Among them, there were no significant differences in neck symptoms between cervical spine instability group and none cervical spine instability group. The patients with cervical spine instability had a longer duration of disease [60 (18,180) months vs.16 (8,51) months], a higher proportion of peripheral joint deformity (63.3%vs.21.3%), and a lower hemoglobin [(106.90±21.61) g/L vs. (115.77±14.69) g/L]. There was no significant difference in the occurrence of cervical instability in the treatment-naive RA patients compared with treated RA patients. Among the RA patients with cervical instability, there was no statistically significant difference in the composition of each type between the patients with treatment-naive RA and patients with treated RA, except for a shorter duration of disease [120.0 (72.0, 240.0) months vs. 60.0 (27.0, 167.5) months]. Conclusion: 28.6% of treatment-naive RA patients showed cervical spine instability. Cervical instability was also common in RA patients with a duration less than 24 months. There was no significant correlation between cervical instability and neck symptoms. Patients with cervical spine instability had a long-term disease, a higher proportion of peripheral joint deformity and a lower hemoglobin. Controlling the condition of RA early may help to control the progression of cervical involvement in patients with RA.

Objective: To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection. Methods: Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn,and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens. Results: A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P<0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P<0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P<0.05). Conclusion: The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Objective: To explore the difference in phenotype recognition of PsA patients in two clinical scenarios, physical examination with and without ultrasound assessment. Methods: PsA patients who visited the rheumatology and clinical immunology department of Peking University First Hospital between January 2010 and October 2020, with complete data of clinical and ultrasound assessment were enrolled. The phenotypes were first identified based on physical examination only, and then combined with enthesitis and dactylitis shown on power doppler and gray-scale ultrasound. The phenotype groupings without and with ultrasound assessment were presented with Wayne diagram. The distributions of different clinical phenotypes were compared by using χ ² test or Fisher’s exact test. The differences of clinical phenotypes with and without ultrasound assessment were compared by using Wilcoxon signed rank test. Results: A total of 227 patients with PsA were enrolled with one or more clinical domains. Physical examination revealed that psoriasis was in 209 (92.1%, 209/227) patients, nail involvement in 98 (43.2%, 98/227) patients, peripheral arthritis in 219 (96.5%, 219/227) patients, axial involvement in 25 (11.0%, 25/227) patients,dactylitis in 80 (35.2%, 80/227) patients, and enthesitis in 18 (7.9%, 18/227) patients. Besides 18 patients with clinical enthesitis, ultrasound scan revealed acute enthesitis in 80 patients, with hypoechogenicity (55 cases), tendon thickening (62 cases), and presence of Doppler signals (48 cases). Similarly, dactylitis on ultrasound was found in 18 patients besides those patients with clinical dactylitis. Compared with the phenotypes recognized based on physical examination only, the additional ultrasound assessment revealed that the most common phenotypes, peripheral arthritis was significantly less frequently recognized (49.8% vs. 27.8%, P<0.001), however on the other hand, the proportion of the patients with peripheral arthritis and enthesitis was significantly increased (4.4% vs. 18.1%, P<0.001). The phenotype of peripheral arthritis combined with enthesitis, and dactylitis was also dramatically increased (1.8% vs. 17.6%, P<0.001). Conclusion: Ultrasound is a useful tool to identify enthesitis and dactylitis. With the aid of ultrasound assessment, rheumatologists can better identify the lesions of PsA, accurately identify the phenotypes, and further guide the subsequent treatment.

Objective: To explore the abnormal manifestations and clinical features of patients with gout according to the location of crystal deposits:in articulars or in tendons. Methods: A total of 105 patients with gout who were continuously treated in the Department of Rheumatology and Immunology of Peking University People’s Hospital from June 2019 to December 2019 were selected and their knees, ankles, toes and painful joints and tendons were examined by high-frequency ultrasound. Then we grouped them according to the presence or absence of sodium urate crystals and the location of the crystals, collected their clinical data, and analyzed the clinical characteristics. Results: Among the 105 patients, 25 patients had no crystal deposits in the joints or tendons (as the non-crystal group), 43 patients had intra-articular crystals (as the joint group), and 37 patients had intra-tendon crystals with or without intra-articular crystals (as the tendon group). Among them, the most involved part of sodium urate crystals deposited in the joints was the metatarsophalangeal joint (29 cases, 67.4%), followed by knee joints (10 cases, 23.2%), ankle joints (9 cases, 20.9%). The most involved part of sodium urate crystals deposited in the tendon was the quadriceps tendon (16 cases, 43.2%), followed by the Achilles tendon (13 cases, 35.1%), the patellar tendon (12 cases, 32.4%), and the three heads of brachii tendons (5 cases, 13.5%). The three groups were compared using multi-sample analysis of variance/multi-sample rank sum test. Age, age of first increase in uric acid (UA), serum glucose (Glu) level and C reactive protein (CRP) were all significantly different. After multiple comparisons, compared with the non-crystal group, age, the age of first increase in uric acid, and CRP were significantly higher in the tendon group. There was no significant difference between the non-crystal group and the joint group. There was no significant difference between the tendon group and the joint group. Conclusion: In patients with gout, it is common for ultrasound to find crystals deposited in joints or tendons. The most commonly affected parts include the metatarsophalangeal joint, knee joint, ankle joint, quadriceps tendon, Achilles tendon, patellar tendon, and triceps tendon. There were significant differences among the three groups in age, age of first increase in uric acid, CRP and blood glucose, and the proportion of urinary calculi in patients with crystal deposits was significantly higher than those without crystal deposits.

Objective: To investigate the clinical characteristics of Henoch-Schonlein purpura (HSP) patients from different altitudes in Tibet plateau areas of China. Methods: A retrospective study was used to analyze the 190 HSP patients admitted to Tibet Autonomous Region People’s Hospital form April 2014 to May 2021. The subjects were divided into 3 groups according to the altitude of long-term residence before onset and the clinical data at different altitudes were compared and analyzed. Results: There were no significant differences in the age of onset and gender in HSP patients at different altitudes (P>0.05). The HSP patients in high altitude areas were more likely to have digestive symptoms (P<0.01). The patients were more likely to have kidney or joint involvement at higher altitudes. The platelets [(512.1±55.0)×10⁹/L] and C reactive protein [11.2 (5.7, 19.4) g/L] in high altitude areas were significantly higher than at medium altitudes [(498.3±76.9)×10⁹/L and 9.5 (4.6, 13.5) g/L] and lower altitudes [(456.4±81.2)×10⁹/L and 3.7 (0.2, 8.9) g/L] respectively. The effective rate of treatment was 98.9%, while there was no significant difference of outcome from different altitudes (P>0.05). The patients who were repeatedly hospitalized all had kidney involvement and no immunosuppressive agents were added in the initial treatment. Conclusion: HSP is common in high altitude areas. There was little difference in age of onset and gender at different altitudes. Abdominal pain was the most common clinical manifestation. Patients in high altitude areas were more likely to have severe abdominal problems. Kidney involvement may be poor prognostic factor. Early application of glucocorticoid combined with immunosuppressive agents can effectively control the disease and reduce the recurrence of HSP.

Objective: To investigate the clinical and immunological features of cardiac involvement in patients with anti-synthetase syndrome (ASS). Methods: In the study, 96 patients diagnosed with ASS hospitalized in the Department of Rheumatology and Immunology, Peking University People’s Hospital from April 2003 to November 2020 were included. The patients were divided into two groups according to whether they were accompanied with cardiac involvement. Demographic features, clinical characteristics (Gottron’s sign/papules, muscle damage, etc.), comorbidities, laboratory indices (creatine kinase, inflammatory indicators, immunoglobulin, complement, lymphocyte subset, autoantibodies, etc.) were collected and the differences between the two groups were analyzed statistically. Results: The prevalence of cardiac involvement in the patients with ASS was 25.0% (24/96). The ASS patients complicated with cardiac involvement presented with elevated cardiac troponin I (cTnI, 75.0%, 18/24), pericardial effusion (33.3%, 8/24), reduction of left ventricular function (33.3%, 8/24) and valves regurgitation (33.3%, 8/24). The age of onset of the patients with cardiac involvement was older than that of the patients without cardiac involvement [(54.58±10.58) years vs. (48.47±13.22) years, P=0.043). Arthritis was observed less frequently in the patients with cardiac involvement than those without cardiac involvement (37.5% vs. 61.1%, P=0.044). In addition, rapidly progressive interstitial lung disease (54.2% vs. 30.6%, P=0.037) was observed more frequently in the patients with cardiac involvement than those without cardiac involvement. As compared with the ASS patients without cardiac involvement, C-reactive protein (CRP) [(13.55 (8.96, 38.35) mg/L vs. 4.60 (1.37, 17.40) mg/L, P=0.001], and lactate dehydrogenase (LDH) [408.0 (255.0, 587.0) U/L vs. 259.5 (189.8, 393.8) U/L, P=0.007] were significantly higher in the patients with cardiac involvement. Anti-Ro-52 antibody was detected more commonly in the ASS patients with cardiac involvement compared with the patients without cardiac involvement (91.7% vs. 69.4%, P=0.029). No significant differences were found in the comorbidities, alanine transaminase (ALT), aspartate transaminase (AST), creatine kinase (CK), erythrocyte sedimentation rate (ESR), ferritin (Fer), immunoglobulin G (IgG), complement 3 (C3), complement 4 (C4), lymphocyte subset between the two groups. Conclusion: Cardiac involvement is common in ASS, mainly manifested as myocardial damage. It is necessary to be aware of cardiac complications in patients with elevated CRP, elevated LDH and positive anti-Ro-52 antibody.

Objective: To investigate the clinical relevance of serum interleukin-2 receptor α (IL-2Rα) in patients with systemic lupus erythematosus (SLE). Methods: One hundred and seven SLE patients and 39 healthy controls with comparable age and gender were recruited at Peking University People’s Hospital from January 2019 to December 2020. Complete clinical data in 107 SLE patients at baseline and follow-up were collected. SLE disease activity index 2000 (SLEDAI-2K) was used to assess the disease activity of the SLE patients. The serum level of IL-2Rα in the SLE patients and healthy controls was measured using enzyme-linked immunosorbent assay (ELISA). The association between serum IL-2Rα and clinical and laboratory parameters was investigated. Mann-Whitney U test or t test, Chi-square test and Spearman correlation were used for statistical analysis. Results: The serum IL-2Rα levels were significantly higher in the SLE patients [830.82 (104.2-8 940.48) ng/L], compared with those in the healthy controls [505.1 (78.65-1 711.52) ng/L] (P<0.001). Association analysis showed that the increased serum IL-2Rα was positively associated with SLEDAI-2K scores and anti-nucleosome antibody (r=0.357, P<0.001; r=0.25, P=0.027, respectively). Thirty-six of 107 (33.6%) SLE patients had lupus nephritis. Serum IL-2Rα levels were significantly higher in the patients accompanied with lupus nephritis [1 102.14 (126.52-8 940.48) ng/L] than in the patients without lupus nephritis [743.89 (104.19-4 872.06) ng/L] (P=0.032). The patients in the high IL-2Rα group had more lupus nephritis compared with those in the low IL-2Rα group (40.8% vs. 19.4%, P=0.031). Meanwhile, SLEDAI-2K scores were found significantly higher in the high IL-2Rα group than in the low IL-2Rα group [10 (3-21) vs. 7 (3-16), P=0.001]. With the improvement of disease activity in the SLE patients after conventional treatments, serum levels of IL-2Rα [1 119.1 (372.25-2 608.86) ng/L] in the week 12 decreased significantly compared with the baseline [1 556.73 (373.08-8 940.48) ng/L] (P=0.042). Conclusion: Serum IL-2Rα may be used as a biomarker of disease activity in patients with SLE. There is certain correlation between serum IL-2Rα and renal involvement in SLE.

Objective: To investigate the clinical and immunological characteristics of overlap myositis (OM) patients. Methods: The data of 368 patients with idiopathic inflammatory myopathies (IIMs) admitted to Peking University People’s Hospital from January 2004 to August 2020 were analyzed retrospectively, including demographic characteristics, clinical characteristics (including fever, Gottron’s sign/papules, Heliotrope rash, V-sign, Shawl sign, Mechanic’s hands, skin ulceration, periungual erythema, subcutaneous calcinosis, dysphagia, myalgia, myasthenia, arthritis, Raynaud’s phenomenon, interstitial lung disease, pulmonary hypertension and myocardial involvement), laboratory characteristics, immunological characteristics [including antinuclear antibodies, rheumatoid factors, myositis-associated autoantibodies (MAAs) and myositis-specific autoantibodies (MSAs)] and survival. The clinical and immunological characteristics and prognostic differences of OM and non-OM were compared. The Kaplan-Meier and Log Rank methods were used to analyze the survival. Results: A total of 368 patients were included. 23.9% (88/368) of IIMs patients were OM patients. Among the 88 OM patients, 85.2% (75/88) of them were female, and the median interval between disease onset and diagnosis was 13.5 months. The incidence of overlapped connective tissue diseases in the OM patients was dermatomyositis (DM) in 60.2%, polymyositis (PM) in 3.4%, immune-mediated necrotizing myopathy (IMNM) in 2.3% and anti-synthetase syndrome (ASS) in 34.1%. Compared with the non-OM patients, the proportion of the females in the OM patients was higher (85.2% vs. 72.1%, P=0.016), the OM patients had longer disease duration [13.5(4.5,48.0) months vs. 4.0(2.0,12.0) months, P<0.001]. As for clinical characteristics, compared with the non-OM patients, the incidence of V-sign (25.0% vs. 44.6%, P=0.001) and periungual erythema (8.0% vs. 19.6%, P=0.013) were lower; the incidence of Raynaud’s phenomenon (14.8% vs. 1.8%, P<0.001), interstitial pneumonia (88.6% vs. 72.1%, P=0.001), pulmonary hypertension (22.7% vs. 7.5%, P<0.001) and myocardial involvement (18.2% vs. 9.3%, P=0.033) were higher. As for immunological characteristics, compared with the non-OM patients, the incidence of elevated aspartate aminotransferase (AST) (31.8% vs. 45.0%, P=0.035) was lower and elevated C-reactive protein (CRP) (58.0% vs. 44.6%, P=0.037) was higher; the positive rates of antinuclear antibodies (ANA) (85.1% vs. 63.4%, P=0.001) and rheumatoid factors (RF) (40.2% vs. 17.8%, P<0.001) and anti-Ro-52 (71.6% vs. 56.1%, P=0.038) in serum were higher. There was no significant difference in the survival between the OM patients and non-OM patients. Conclusion: Pulmonary hypertension and myocardial involvement were frequently observed in OM.

Objective: To assess the activation function of specific tumor polypeptide for dendritic cell vaccine on lymphocytes proliferation, production of cytokines and killing activity in vitro by using dendritic cells as antigen presenting vector. Methods: Peripheral blood dendritic cells (DC) and cytokine-induced killer (CIK) were isolated and cultured by adherent culture method; CCK-8 method was used to assess the proliferation function of lymphocytes and the killing function of lymphocytes to tumor cells; enzyme-linked immunospot assay method was used to evaluate the secretion function of cytokines. The experiment was divided into tumor polypeptide group (peptide with DC-CIK), DC-CIK group and CIK group. Results: With presence of interleukin-2 (IL-2) in the culture system, the lymphocyte proliferation of the three groups was obvious. The absorbance at 450 nm of tumor polypeptide group was significantly higher than that of CIK group at the time points day 4 and day 6 (day 4: Z=-3.79, P<0.001; day 6: Z =-2.95, P< 0.01). The absorbance at 450 nm of group tumor polypeptide was significantly higher than that of DC-CIK group on day 4 (Z=-2.02, P<0.05). Without IL-2 in the culture system, lymphocytes proliferated slowly in all the three groups, and there was no significant difference in 450 nm absorbance at each time point. The levels of IL-4 (Z=-2.61, P< 0.01), granulocyte-macrophage colony-stimulation factor (GM-CSF, Z=-3.85, P< 0.001), interferon- γ (IFN- γ, Z=-3.56, P< 0.001) and tumor necrosis factor-α (TNF-ɑ, Z=-3.40, P< 0.001) of tumor polypeptide group were higher than those of CIK group. There was no significant difference in the production of cytokines except IL-4 (Z=-2.15, P< 0.05) when tumor polypeptide group was compared with DC-CIK group. The production of IFN-γ (Z=-2.44, P<0.05), TNF-ɑ (Z=-2.26, P< 0.05) and GM-CSF (Z=-3.73, P< 0.001) in DC-CIK group were higher than those of CIK group. Although there was no significant difference in killing activity between tumor polypeptide group, DC-CIK group and CIK group at hour 18 and hour 24, and the killing activity of tumor polypeptide group was higher than that of the other two groups. Conclusion: Tumor peptide combined with dendritic cells can improve the proliferation activity of CIK cells in vitro, and increase the secretion of several cytokines.

Objective: Bietti crystalline dystrophy (BCD) is a rare degenerative eye disease caused by mutations in the CYP4V2 gene, and Cyp4v3 is the murine ortholog to CYP4V2. To better understand the molecular pathogenesis of this disease and to explore the potential treatment we have established a Cyp4v3 knock-out mouse model. Methods: Cyp4v3 ^-/- mice were generated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 in embryonic stem cells of C57BL/6J mice. Ocular morphologic characteristics were evaluated via fundus imaging, histologic analysis of rods and cones via immunofluorescence, and phalloidin stain to observe retinal pigment epithelium (RPE) in whole-mounts, electroretinogram (ERG) was also conducted to examine the retinal function. Results: The characteristic features of BCD recurred in the Cyp4v3 ^-/- mice, including retinal crystalline deposits, atrophy and degeneration of RPE cells, and ERG amplitude decline of dark and light adapted a- and b- wave; however, the immunofluorescence stain of rod and cone cells did not show obvious differences when compared with the wild type (WT) mice. In the early stage of the disease, no crystal-like deposits were found in the fundus, ERG detection of the retinal function did not find a significant decline, and the morphological structure and quantity of the neural retina and RPE did not change significantly. Crystalline deposits occurred and converged when the Cyp4v3 ^-/- mice at the end of 6 months, and the deposits disappeared when the Cyp4v3 ^-/- mice at the end of 12 months. The ERG amplitude started to decline when the Cyp4v3 ^-/- mice at the end of 6 months and deteriorated at the end of 12 months. The RPE cells of the 12-month old Cyp4v3 ^-/- mice showed irregular shape by phalloidin staining of F-actin. The Cyp4v3 ^-/- mice behaved normally and were viable and fertile when maintained under specific pathogen-free (SPF) housing conditions. Conclusion: Just like BCD patients, the disease progress of Cyp4v3 ^-/- mouse is correlated with the age, which provides a good model for pathogenesis and gene therapy study in the future. The atrophy and degeneration of RPE take the lead in progressing of the disease, but the mechanism is not clear yet.

Objective: To investigate evodiamine (EVO)-induced hepatotoxicity and the underlying mechanism. Methods: HepG2 cells were treated with EVO (0.04-25 μmol/L) for different time intervals, and the cell survival rate was examined by cell counting kit-8 (CCK-8) method. After HepG2 cells were treated with EVO (0.2, 1 and 5 μmol/L) for 48 h, the alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP) activities and total bilirubin (TBIL) content of supernatant were detected. A multifunctional microplate reader was used to detect the intracellular superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in HepG2 cells to evaluate the level of cell lipid peroxidation damage. The interactions between EVO and apoptosis, autophagy or ferroptosis-associated proteins were simulated by molecular docking. The HepG2 cells were stained by mitochondrial membrane potential (MMP) fluorescent probe (JC-10) and annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI), and MMP and apoptosis in HepG2 cells were detected by flow cytometry. The protein expression levels of caspase-9, caspase-3, bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2) were detected by Western blot. Results: The cell survival rate was significantly reduced after the HepG2 cells were exposed to EVO (0.04-25 μmol/L) in a time- and dose-dependent manner. The half maximal inhibitory concentration (IC50) of the HepG2 cells treated with EVO for 24, 48 and 72 h were 85.3, 6.6 and 4.7 μmol/L, respectively. After exposure to EVO (0.2, 1 and 5 μmol/L) for 48 h, the ALT, AST, LDH, ALP activities and TBIL content in the HepG2 cell culture supernatant, and the MDA content in the cells were increased, and SOD enzyme activity was decreased. Molecular docking results showed that EVO interacted with apoptosis-associated proteins (caspase-9 and caspase-3) better. JC-10 and Annexin V-FITC/PI staining assays demonstrated that EVO could decrease MMP and promote apoptosis in the HepG2 cells. Western blot results indicated that the protein expressions of cleaved caspase-9 and cleaved caspase-3 were upregulated in the HepG2 cell treated with EVO for 48 h. In contrast, the protein expressions of pro-caspase-3, BSEP and MRP2 were downregulated. Conclusion: These results suggested that 0.2, 1 and 5 μmol/L EVO had the potential hepatotoxicity, and the possible mechanism involved lipid peroxidation damage, cell apoptosis, and cholestasis.

Objective: To explore the characteristics of gastric microbiota in children with and without (Helicobacter pylori, H. pylori) infection who had family history of H. pylori infection. Methods: Mucosal biopsy samples of the gastric corpus and gastric antrum were collected during the gastroscope. And the gastric mucosa flora’s information of the two groups of children were obtained after sample DNA extraction, PCR amplification of the 16S ribosomal DNA (rDNA) V3-V4 region, high-throughput sequencing and data processing. All the samples with family history of H. pylori infection were divided into two groups, the H. pylori infection group (n=18) and the H. pylori non-infection group (n=24). Then the α-, β-diversity and bacteria abundance of the gastric microbiota were compared between the H. pylori infection and non-infection groups at different taxonomic levels. The differential microbiota was found out by LEfSe analysis, and then the function of microbiota predicted using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) method. Results: There was statistically significant difference in α-diversity (P<0.05) between the two groups, indicating that the H. pylori non-infection group had higher microbial richness than the H. pylori infection group. Moreover, the β-diversity was significantly different as well (P<0.05), which meant that the microbiota composition of the two groups was different. At the phyla level, Proteobacteria, Firmicutes, Bacteroides, Actinobacteria, and Fusobacteria were dominant in the two groups. At the genus level, Bacteroides, Prevotella, Streptococcus, and Neisseria, etc. were dominant in the H. pylori non-infected group. Meanwhile, Helicobacter and Haemophilus etc. were dominant in the H. pylori infected group. LEfSe analysis showed that the relative abundance of Bacteroides etc. at the genus level in the H. pylori non-infected group was significantly higher than that in the H. pylori infected group. Functional prediction showed that Bacteroides were positively correlated with amino acid and vitamin metabolism, mitogen-activated protein kinase (MAPK), mammalian target of rapamycin (mTOR) signaling pathway and ansamycin synthesis pathway. Conclusion: The gastric microbiota between H. pylori positive and H. pylori negative in children with family history of H. pylori infection is significant different. Some gastric microbiota, such as Bacteroides, may have a potential relationship with H. pylori infection in children.

Objective: To investigate the endoscopic and pathological characteristics of gastric adenomatous polyps and to assess the potential risk factors for canceration of gastric adenomatous polyps. Methods: The endoscopic and pathological characteristics of the patients with gastric adenomatous polyps from January 1, 2005 to December 31, 2019 were summarized retrospectively, and the risk factors of canceration were analyzed. Results: A total of 125 patients with gastric adenomatous polyps were included, 51.20% of whom were females. The average age was (66.7±12.3) years. 64.80% of patients with gastric adenomatous polyps equal or more than 65 years old, and only 5.60% of the patients less than 45 years old. Adenomatous polyps were mostly distributed in the corpus and antrum with 40.80% and 32.80%, respectively. The majority of them were single (90.40%) and sessile (76.81%). 65.4% of adenomatous polyps were no more than 1.0 cm in diameter, and 23.20% of patients with adenomatous polyps were combined with hyperplastic polyps and/or fundus glandular polyps, and 1.60% had both pathological types of polyps. 58.62% (17/29) patients with hyperplastic polyps and/or fundus glandular polyps had multiple polyps. 1.60% (2/125) of the patients had gastric neuroendocrine tumor of G1 stage. Synchronous gastric cancer was detected in 13.60% (17/125) of the patients with adenomatous polyps, and the proportion of low-grade intraepithelial neoplasia was 18.40% (23/125). The main types of synchronous gastric cancer were progressive (70.59%) and undifferentiated (66.67%). Chronic atrophic gastritis with intestinal metaplasia was found in 52.80% of the patients, and autoimmune gastritis accounted for 11.20%. The positive rate of Helicobacter pylori was 21.60%. The canceration rate of gastric adenomatous polyps was 20.80%. The cancer was mainly differentiated, but there was sigmoid ring cell carcinoma as well. Diameter of >1.0 cm (OR=5.092, 95%CI: 1.447-17.923, P=0.011), uneven surface morphology and erosion (OR=13.749, 95%CI: 1.072-176.339, P=0.044) were independent risk factors of adenomatous polyps. Conclusion: The synchronous gastric cancer is common and the canceration of gastric adenomatous polyps is high with diameter and surface morphology as independent risk factors. We should pay attention to the identification of the pathological types of polyps and the evaluation of the whole gastric mucosa during the endoscopic examination.

Objective: To analyze the clinical characteristics of aldosterone-producing adenoma (APA) subtypes in primary aldosteronism (PA) and the application value of captopril challenge test (CCT) in adenomas. And to find out the clinically specific non-invasive index for identifying APA subtypes from PA. Methods: The clinical data of hospitalized patients with hypertension were retrospectively collected. All the patients were conducted with the CCT and 90 patients with PA were confirmed. Among them, 34 patients were confirmed to have APA by surgery. The clinical indicators of the two groups of patients including plasma aldosterone concentration (PAC), aldosterone inhibition rate (%), and aldosterone to renin ratio (ARR) before and after the CCT were compared, the receiver operating characteristic (ROC) curves for the relevant indicators before and after the CCT drawn, and the areas under the curve (AUC) compared. The ROC curves were used to analyze the efficiency of the different CCT diagnostic criteria for diagnosing APA. Results: Compared with the PA group, the duration of hypertension was shorter, the incidence of hypokalemia was higher, and the average serum potassium level was lower when APA was diagnosed. There were no significant differences in blood pressure level, gender, serum sodium and body mass index between the two groups. Compared with PA population, APA group had higher PAC and ARR whether before or after the CCT, but lower plasma renin concentration (PRC). In APA patients, the mean degree of PAC declined after CCT was approximately 5.7%, but 5% with that of PA. As for diagnosing, ARR before or after CCT had diagnostic value for APA, in which the ARR cut-off point was 7.12, which yielded a sensitivity and specificity of 35.85% and 77.78%. The cut-off point of ARR after CCT was 4.23, with a sensitivity of 71.43% and specificity of 62.22%. For the diagnosis, the ARR before and after CCT were of no significant difference. However, the diagnostic specificity of ARR>7.12 combined with hypokalemia was up to 80%. Conclusion: ARR before or after CCT have clinical value for the diagnosis of APA from PA, when combined with hypokalemia yielded high specificity.

Objective: To investigate the presentation of susceptibility vessel sign (SVS) in subacute stroke patients with large vessel occlusion. Methods: We collected consecutive stroke patients who were admitted to Peking University First Hospital from December 2017 to August 2019 retrospectively. Those who had intracranial large vessel occlusion and received sensitivity weighted imaging (SWI) within 3 to 14 days after stroke onset were included in our analysis. The diagnosis of large vessel occlusion was based on magnetic resonance angiography (MRA), CT angiography (CTA) or digital subtraction angiography (DSA). The demographic information, clinical characteristics and imaging results were obtained from medical record. The occurrence rates of SVS sign were compared between stroke patients with cardioembolism (CE) and large artery atherosclerosis (LAA). In the sensitivity analysis, we performed a subgroup analysis in those patients who received SWI within 7 to 14 days after stroke onset. We also compared the occurrence rate of SVS sign between the patients with and without atrial fibrillation. Results: A total of 51 patients, 19 females and 32 males, with an average age of (63.04±11.23) years were analyzed in this study. Compared with LAA group, the patients in CE group were older and more likely to have an atrial fibrillation (P<0.05). There were no significant differences between the CE group and LAA group in gender, hypertension, diabetes, coronary heart disease, hyperlipidemia, smoking, or National Institute of Health stroke scale(NIHSS) score at admission. SVS sign was found in 30 patients. Of whom, 3 were in CE group and 27 in LAA group. The occurrence rate of SVS sign was higher in the LAA group than in the CE group significantly (65.9% vs. 30.0%, P=0.039). The subgroup analysis showed that, in the patients who received SWI examination within 7 to 14 days after stroke onset, the differences between the two groups were still statistically significant (0 vs. 72.7%, P=0.006). Another sensitivity analysis showed that, the rate of SVS in the patients with atrial fibrillation was significantly lower than those patients without atrial fibrillation (25% vs. 65.1%, P=0.043). Conclusion: In subacute stroke patients, the occurrence rate of SVS sign in CE group was lower than that of LAA group. The significance of SVS sign in the differentiation of stroke subtype needs further validation.

Objective: To study the relationship between preoperative plasma interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), homocysteine (Hcy), endothelin-1 (ET-1) levels and new-onset atrial fibrillation (AF) after coronary artery bypass grafting (CABG). Methods: In the study, 148 patients who underwent isolated CABG in Peking University People’s Hospital from January 1, 2017 to December 30, 2017 were enrolled, of whom 39 had new-onset AF. The fasting venous blood was collected within 24 hours before the surgery. The preoperative plasma IL-1, IL-6, TNF-α, Hcy, ET-1 levels were detected by enzyme-linked immunosorbent assay (ELISA). The patients were divided into AF group and non-AF group according to whether new-onset AF occurred after operation. After 1 ∶1 propensity score matching (PSM), 38 people were in each group. The paired sample t-tests were performed on the five factors’ concentrations of the matched AF group and the non-AF group respectively. If the concentration values did not conform to the normal distribution, the Wilcoxon signed rank sum test was performed. Conditional Logistic regression analysis was performed on the concentrations of the five indicators to explore the correlation between preoperative plasma concentrations of IL-1, IL-6, TNF-α, Hcy, ET-1 and postoperative new-onset AF after CABG. Results: After a 1 ∶1 propensity score matching, the AF group was comparable to the non-AF group. The concentrations of IL-1, IL-6, TNF-α, and Hcy in the AF group were higher than those in the non-AF group [(0.867±0.589) ng/L vs. (0.742±0.262) ng/L, 21.55 (6.50, 209.90) ng/L vs. 17.95 (3.60, 86.70) ng/L, 20.30 (5.70, 361.00) ng/L vs. 21.50 (7.50, 251.80) ng/L, (0.29±0.11) μmol/L vs. (0.27±0.09) μmol/L], but the differences were not statistically significant (P=0.165, P=0.891, P=0.817, P=0.285). After the conditional Logistic regression analysis, the above four variables were not predictors of new-onset AF after CABG. The concentrations of ET-1 in the matched AF group and non-AF group were (25.80±6.20) ng/L and (29.10±8.54) ng/L, respectively. The correlation between preoperative low plasma ET-1 concentration and the new-onset AF after CABG were statistically significant (P=0.003). After conditional Logistic regression analysis, preoperative plasma ET-1 concentration was correlated with postoperative new-onset AF after CABG (P=0.039, adjusted OR=0.637, 95%CI: 0.415-0.977). Conclusion: The levels of preoperative plasma IL-1, IL-6, TNF-α and Hcy in the patients with new-onset AF after CABG were higher than those in the patients without AF, but the difference was not statistically significant. Preoperative plasma low ET-1 concentration was statistically associated with new-onset AF after CABG.

Objective: The key point of anesthesia management in carotid endarterectomy (CEA) is to maintain adequate cerebral perfusion during carotid artery occlusion. Placement of shunt is one of the common surgical methods. This study analyzed the effects of different shunt strategies on cerebral infarction after carotid endarterectomy. Methods: A total of 443 patients who underwent CEA under general anesthesia within 2 years were divided into imaging group (based on preoperative imaging data as the basis for shunt) and stump pressure group (based on intraoperative stump pressure as the basis for shunt). The preoperative demographic data, past medical history, degree of cervical vascular stenosis, blood pressure at each time point during the perioperative period, vascular blocking time, whether to place the shunt, postoperative hospital stay, cerebral infarction during hospitalization, and other adverse events were collected and compared between the two groups. On this basis, the preoperative and intraoperative conditions with significant differences were matched with propensity scores, and the influence of different shunt strategies on postoperative cerebral infarction was analyzed. Results: In the study, 268 patients in the imaging group and 175 patients in the stump pressure group underwent CEA under general anesthesia. There were statistically significant differences in basic conditions and blood pressure at each time point between the two groups. After matching the propensity scores, 105 patients in each of the two groups were matched. The basic conditions of the patients before surgery and the difference in blood pressure of the two groups at each time point were not statistically significant. There was no significant diffe-rence in the incidence of postoperative cerebral infarction between the two groups (1.9% vs. 1.0%, P>0.999). The intraoperative shunt rate in the imaging group was lower than that in the stump pressure group (0 vs. 22.9%, P<0.001). The postoperative hospital stay in the imaging group was 8 (7, 8) days, which was longer than the stump pressure group 5 (4, 6) days (P<0.001). Conclusion: The rate of the shunt was lower according to preoperative imaging examination than that according to the residual pressure in our hospital. There is no significant difference in the incidence of cerebral infarction during the postoperative hospital stay. The effect of different shunt strategies on cerebral infarction needs further study.

Objective: To investigate the effect of epidural anesthesia on the long-term prognosis of patients after selective colorectal cancer resection surgery. Methods: This was a retrospective cohort study and approved by local institution review board. Patients who underwent selective colorectal cancer resection surgery from August 2011 to December 2012 in Peking University First Hospital were enrolled. The patients were divided into general anesthesia (GA) group and combined epidural-general anesthesia (EGA) group according to anesthesia type. Primary outcome was patient’s long-term survival status. Secondary outcome included the overall incidence of in-hospital complications and length of postoperative in-hospital stay. Propensity score was used to match cases between the two groups based on the probability of receiving EGA. Survival was analyzed by Kaplan-Meier analysis and compared by Log-rank test between the two groups. Multivariate Cox regression analysis was used to investigate the relationship between epidural anesthesia and other variables with long-term survival status. Results: A total of 264 patients were entered into final analysis, including 166 cases in GA group and 98 cases in EGA group. Mean age of the patients was (63.3±12.1) years and mean survival time was 47.2 (95%CI 45.7-48.7) months. Before the propensity score match, the mortality in EGA group was 16.9% (28/166) and 9.2% (9/98) in GA group. But comparison between the two groups had no statistical significance (P=0.091). After the propensity score match,87 paired cases were matched and analyzed. The risk of long-term mortality in EGA group was lower than that of GA group by Kaplan-Meier analysis (5.7% vs.16.1%, HR=0.344, 95%CI 0.124-0.955, P=0.041). Mean survival time of EGA group was longer than that of GA group (50.3 months vs. 42.9 months, P=0.032). Multivariate Cox regression ana-lysis showed that EGA, in comparison with GA, was related with lower risk of long-term mortality (HR=0.326, 95%CI 0.117-0.909, P=0.032). Age (HR=1.042, 95%CI 1.001-1.085, P=0.046) and preoperative lymph node metastasis (HR=2.924, 95%CI 1.162-7.356, P=0.023) were also related with increased risk of long-term mortality. Conclusion: Present study found that perioperative use of epidural anesthesia and analgesia was associated with improvement of the patient’s long-term survival. Well-designed studies are needed to verify this hypothesis.

Objective: To evaluate the effectiveness and safety of Rotarex mechanical thrombectomy system in treating acute lower limb ischemia. Methods: From December 2017 to December 2019, the clinical data of 23 acute lower limb ischemia cases treated with Rotarex mechanical thrombectomy system were retrospectively analyzed. There were 14 males and 9 females from 53- to 84-year-old patients and the mean age was (69.1±9.1) years. Duration of symptoms was 6 hours to 14 days (median time: 7 days). In the study, 8 acute thromboembolism cases and 15 acute thrombosis cases were included (In which, there was one thromboangiitis obliterans case and two in-stent restenosis cases). In 5 cases, the lesions were located above the groin; in 16 cases, the lesions were located below the groin, and in the other 2 cases, the lesions were located both above and below the groin. All the cases were treated with Rotarex mechanical thrombectomy system. When residual stenosis was greater than 50%, percutaneous transluminal angioplasty (PTA) was used, and stent was used only when it was necessary. Heparin was used 24 h after the procedure, and after that, antiplatelet agents were used in acute thrombosis cases, and oral anti-coagulants were used in acute thromboembolism cases. Doppler ultrasonography was taken during the follow-up. Results: In all the 23 cases, there were 22 successful cases and 1 unsuccessful case, the mean procedure time was (68.2±15.6) min. Percutaneous transluminal angioplasty was used in 18 cases, 7 of which were implanted stents (3 stents were implanted in iliac artery and 4 in superficial femoral artery). There were 3 procedure related complications. The first one was arterial wall injury which resulted in contrast medium extravazation, and in this case, we solved it with prolonged balloon inflation. The second one was distal embolism. We took out the thrombus with guiding catheter. The last one was acute occlusion in a stent, and thrombectomy was applied urgently, and the result was good. Mean hospital stay were (3.6±1.7) days. The ankle brachial index (ABI) increased from 0.25±0.10 to 0.85±0.16 after treatment (t=12.901, P<0.001). All the patients were followed up for 4.0-28.0 months, and the median time was 12.0 months. One patient stopped antiplatelet agents, which resulted in acute thrombosis 2 months later. Another percutaneous mechanical thrombectomy and PTA were taken. In the failed case, the patient suffered amputation above the knee 3 months later and in another case, the patient died of heart failure 8 months after the procedure. Two target lesion restenosis occurred during the follow-up. Because the patients’ symptom was not sever, no procedure was taken. Conclusion: Percutaneous mechanical thrombectomy using Rotarex catheter is safe and effective in treating acute lower limb ischemia. For one side, it can restore blood flow to the affected limbs quickly, and for the other, it has the characteristics of minimally invasive and good repeatability. So it should be considered that this me-thod can be widely used for acute lower limb ischemia.

Objective: To construct length of intensive care unit (ICU) stay (LOS-ICU) prediction models for ICU patients, based on three machine learning models: support vector machine (SVM), classification and regression tree (CART), and random forest (RF), and to compare the prediction perfor-mance of the three machine learning models with the customized simplified acute physiology score Ⅱ(SAPS-Ⅱ) model. Methods: We used medical information mart for intensive care (MIMIC)-Ⅲ database for model development and validation. The primary outcome was prolonged LOS-ICU(pLOS-ICU), defined as longer than the third quartile of patients’ LOS-ICU in the studied dataset. The recursive feature elimination method was used to do feature selection for three machine learning models. We utilized 5-fold cross validation to evaluate model prediction performance. The Brier value, area under the receiver operation characteristic curve (AUROC), and estimated calibration index (ECI) were used as perfor-mance measures. Performances of the four models were compared, and performance differences between the models were assessed using two-sided t test. The model with the best prediction performance was employed to generate variable importance ranking, and the identified top five important predictors were pre-sented. Results: The final cohort in our study consisted of 40 200 eligible ICU patients, of whom 23.7% were with pLOS-ICU. The proportion of the male patients was 57.6%, and the age of all the ICU patients was (61.9±16.5) years. Results showed that the three machine learning models outperformed the customized SAPS-Ⅱ model in terms of all the performance measures with statistical significance (P<0.01). Among the three machine learning models, the RF model achieved the best overall performance (Brier value, 0.145), discrimination (AUROC, 0.770) and calibration (ECI, 7.259). The calibration curve showed that the RF model slightly overestimated the risk of pLOS-ICU in high-risk ICU patients, but underestimated the risk of pLOS-ICU in low-risk ICU patients. Top five important predictors for pLOS-ICU identified by the RF model included age, heart rate, systolic blood pressure, body tempe-rature, and ratio of arterial oxygen tension to the fraction of inspired oxygen(PaO₂/FiO₂). Conclusion: The RF algorithm-based pLOS-ICU prediction model had a best prediction performance in this study. It lays a foundation for future application of the RF-based pLOS-ICU prediction model in ICU clinical practice.

Objective: To investigate the effect of local administration of deferoxamine mesylate (DFO) on vascularization and osteogenesis and its ability to maintain the activity of hypoxia inducible factor-1α (HIF-1α), by constantly observing early changes of vessel-like structures and bone tissues during bone defects healing. Methods: Skull critical bone defect models were constructed on a total of thirty male SD rats (6-8 weeks old). The rats were randomly divided into experimental group (DFO group) or control group (normal saline group). 300 μL 200 μmol/L DFO solution or normal saline was locally injected on the 4th day after the defect was made. On the 5th, 7th, 10th, 14th, and 28th days after surgery, three rats in each group were sacrificed respectively. HE staining and Masson staining were performed to observe new bone formation and mineralization. HIF-1α immunohistochemistry staining was performed to examine relative expression of protein. Qualitative analysis and comparation were performed by t-tests on relative expression of HIF-1α, numbers of blood vessels and percentages of mineralization tissues of new bone areas. Results: On the 5th, 7th, 10th, 14th and 28th days after surgery, the average numbers of blood vessels were 30.40±12.15, 62.00±17.87, 73.43±15.63, 40.00±7.84, 48.71±11.64 in the DFO group, and 18.75±6.63, 19.13±2.80, 51.35±16.21, 27.18±7.32, 30.88±13.43 in the control group. The number of blood vessels in the DFO group was significantly higher than that of the control group at each time point (P<0.05). The mass of new bone in the DFO group was higher than that in the control group on the 14th and 28th days after surgery. The percentage of mineralization tissues of new bone area on the 14th and 28th days after injection were (27.73±5.93)% and (46.53±3.66)% in the DFO group, and (11.99±2.02)% and (31.98±4.22)% in the control group. The percentage of mineralization tissues in the DFO group was significantly higher than that of the control group at each time point (P<0.001). The relative expression of HIF-1α in the DFO group compared with the control group was 2.86±0.48, 1.32±0.26, 1.32±0.32, 1.28±0.38 and 1.05±0.34 on the 5th, 7th, 10th, 14th and 28th days, with significant expression difference on the 5th day (P<0.01). Conclusion: Use of DFO in bone defects promotes vascularization and osteogenesis in the defect area, and maintains the protein activity of HIF-1α temporarily.

Testicular rhabdomyosarcoma is relatively rare in testicular tumors, but the age of patient is relatively young and the degree of malignancy is high. Therefore, this article introduces 4 cases of testicular rhabdomyosarcoma who were admitted to Peking University Third Hospital from May 1994 to February 2019, and reviews the literature to improve the diagnosis and treatment of this disease. The average age of the 4 patients was 17.5 years (14-21 years), the average hospital stay was 22.0 d (17-31 d), and the average body mass index was 19.6 kg/m² (14.7-25.8 kg/m²). All the patients underwent routine preoperative blood and urine routine, biochemical tests, as well as serum tumor markers. Preoperative examinations also included chest radiograph, electrocardiogram, ultrasound of the scrotum and groin, and abdominal enhanced CT. Lung CT or other examinations were performed if necessary. The median serum human chorionic gonadotropin (HCG) of the 4 patients was 0.20 IU/L (0.06-0.86 IU/L) (all normal), and the median serum alpha-fetoprotein (AFP) was 1.03 g/L (0.65-1.66 g/L) (all normal). The average maximum diameter of the tumor was 10.0 cm (4.5-15.0 cm). Testicular rhabdomyosarcoma was mainly diagnosed by pathology. The main treatment was radical orchiectomy combined with retroperitoneal lymph node dissection, with or without postoperative adjuvant chemotherapy. The clinical manifestations of the patients with testicular rhabdomyosarcoma had no specific characteristics, but most patients were young at onset with mainly painless masses in the testicles, which were already large when they were found. Patients with testicular rhabdomyosarcoma have a poor prognosis, most of whom recur within two years. Because of the small number of cases of testicular rhabdomyosarcoma, there is no standard treatment currently. It is recommended that patients with testicular rhabdomyosarcoma undergo radical testicular resection combined with retroperitoneal lymph node dissection. Retroperitoneal lymph node metastasis is an important prognostic factor, and patients with postoperative adjuvant chemotherapy can still survive for a longer time. If local recurrence or limited metastasis is found after operation, local resection and salvage radiotherapy are feasible.

A 65-year-old woman developed erythema, papules and nodules over the body. Some nodules of her auricles and hands like string beads. Besides, she suffered from symmetrical swelling and pain of multiple joints, morning stiffness with deformity of joints; She had elevated erythrocyte sedimentation rate and C reactive protein levels; Her rheumatoid factor and antinuclear antibody were positive; Joints destruction was found with X-ray imaging; Skin pathology showed Dermal infiltrate of abundant histiocytes, part of them with a ground-glass appearance; A CD68 immunohistochemical stain was positive and the cells were negative for S100, CD1a. These findings were diagnostic evidences of multicentric reticulohistiocytosis (MRH). The patient received high-dose of glucocorticoids combinated with immunosuppressive agents, and achieved a satisfactory effect. MRH was a rare multisystem disease characterized by papulonodular mucocutaneous and destructive arthritis, and its pathogeny was not yet completely understood. The typical lesions of MRH were hard papules or nodules that usually occured on the hands, face and arms. Classic coral bead appearance from periungual cutaneous nodules that were characteristic of MRH. MRH was an inflammatory joint disease, affecting almost all the appendicular joints and characterized by joint multiple, symmetrical, destructive, progressive disability. Joints destruction of the distal interphalangeal joints was a unique feature of MRH. In addition to skin and joints, it could also involve other systems. There were no diagnostic laboratory markers for MRH. Laboratory examinations had often been found to be non-specific. Imageological examination mainly showed bone and joint destruction. Skin biopsy was the best test to diagnose MRH,the typical histopathological findings included an infiltrate with histiocytes and multinucleated giant cells with a ground-glass appearing in eosinophilic cytoplasm, and the immunohistochemical stain was positive for CD68. The diagnosis was typically made based on the clinical presentation, supportive radiographic findings and skin biopsy. MRH was easily possible to mistake for other more common autoimmune conditions, such as rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and dermatomyositis, but the distinctive clinical, radiographic, and histologic features could aid in differentiating these diseases. MRH could mimic other rheumatic diseases, besides, it could also coexist with cancer or other autoimmune disorders. There was no standardized treatment for MRH. However, Nonsteroidal anti-inflammatory drugs,glucocorticoid, Immunosuppressant,biologic medications, and bisphosphonates had been used with varying degrees of curative effect. Treatment with glucocorticoid combined with immunosuppressants were effective for rash and arthritis, early use of them should be strongly considered,and refractory cases could be treated with biological agents. By reporting a MRH case and reviewing literature, this paper aims to help the clinicians improve the understanding of this rare disease, and suggests that when one diagnosis cannot explain the whole picture of the disease, and further evidence should be sought to confirm the diagnosis.

Colchicine plays an important role in the treatment of gout and some other diseases. Besides gastrointestinal symptoms, myopathy has been reported as a rare side effect of colchicine in some patients. We report a case of myopathy in a patient with chronic kidney disease caused by high-dose colchicine, and then review literature on colchicine-induced myopathy, so as to provide some experience for the clinical diagnosis, treatment and medication safety. A 51-year-old male patient with 10 years of gout and 5 years of chronic kidney disease history and irregular treatment was admitted to the hospital with complaint of recurrent left wrist arthralgia and emerging lower extremities myalgia after intake of 40-50 mg colchicine in total within 20 days. Laboratory examinations showed significantly increased creatine kinase (CK) and then colchicine-induced myopathy was diagnosed preliminarily. After withdrawl of colchicine and implementation of hydration, alkalization and intramuscular injection of compound betamethasone, the symptoms of arthralgia and myalgia were relieved within 3 days and CK decreased to normal range gradually. According to literature reports, colchicine related myopathy was mostly characterized by proximal myasthenia and myalgia, accompanied by elevated CK level, which usually occurred days to weeks after initial administration of colchicine at the usual dosage in patients with renal impairment or a change in the underlying disease state in those receiving long-term therapy, and the features might remit within three to four weeks after the drug was discontinued. Electromyography of proximal muscles showed myopathy marked by abnormal spontaneous activity and muscle pathology waa marked by accumulation of lysosomes and autophagic vacuoles. Chronic kidney disease, liver cirrhosis, higher colchicine dose and concomitant cytochrome P450 3A4 (CYP3A4) inhibitors were associated with increased risk of myo-pathy. Based on the similar efficacy and lower adverse reaction rate compared with larger dosage, small dose of colchicine was recommended by many important current guidelines and recommendations in the treatment of gout. In consideration of potential risks, colchicine should be used with caution in patients with kidney or liver impairment, and in those taking CYP3A4 or P-glycoprotein inhibitors. For those patients, the drug dose should be adjusted and the latent adverse reactions should be monitored carefully.

Idiopathic inflammatory myopathies are a group of rare but serious diseases. The treatment of refractory idiopathic inflammatory myopathy is always challenging, especially in children. Three cases of refractory idiopathic inflammatory myopathy treated by rituximab were reported and discussed with the review of relevant literature. All were female with on-set age of 8 years and 6 months, 11 years and 7 months, 4 years and 2 months old, respectively. All had acute onset, presenting with progressive and severe muscle weakness. All lost ambulation within 1 or 2 months, with difficult swallowing and low voice. Respiratory distress occurred in case 2 after an attack of asphyxia due to an aspiration of sputum, and ventilator support was required for 1 month. Rashes were detected at the initial stage of the disease in cases 2 and 3. Patient 2 showed facial erythematous papules, spreading to her neck and hands. Patient 3 showed purplish eyelids with peri-orbital swelling, generalized edema involving all her limbs. Creatine kinase (CK) levels were markedly elevated in all the patients, ranging from 6 000 IU/L to 28 819 IU/L. Anti-SRP antibody was identified in cases 1, and anti-NXP2 antibodies were confirmed in cases 2 and 3. MRI of both thighs in all the patients showed profound muscle and fascial edema. Muscle pathology of patient 1 showed prominent fiber variation and endomysial fibrosis, with overexpression of MHC-Ⅰ. While muscle pathology in patients 2 and 3 showed scattered fiber necrosis, regeneration, endomysial edema without inflammatory cell infiltration. All the patients were diagnosed with idiopathic inflammatory myopathy and failed to the initial treatment including adequate glucocorticoids and high-dose immunoglobulin therapy. Other immunosuppressants (methotrexate, cyclophosphamide) were also tried in cases 2 and 3 with poor response. Then all the patients were treated with rituximab combined with glucocorticoids. Patient 1 regained normal strength and discontinued rituximab at the end of her last follow-up (2 years and 7 mouths). Though calcinosis developed during the follow-up period, significant improvement was noticed in cases 2 and 3 (both regained the ability to walk independently) at the end of their last follow-up after 2 years and 8 months, 3 years and 2 months respectively. Long-term rituximab therapy may improve the prognosis of refractory idiopathic inflammatory myopathy, especially with positive anti-SRP and anti-NXP2 antibodies.

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient’s vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal β-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with “follicular bronchiolitis” as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.

We report one case of estimated glomerular filtration rate (eGFR) decline after taking unilateral adrenalectomy due to aldosterone adenoma. A 60-year-old male with 23-year history of hypertension was reported to the endocrinologist due to hypokalemia (serum potassium 3.01 mmol/L). Urine microalbumin / creatinine (ALB/CR) was 70.15 mg/g, serum creatinine was 82 μmol/L and eGFR was 89.79 mL/(min·1.73 m ²). Random serum aldosterone was 172.2-203.5 ng/L, and random plasma rennin activity was 0-0.17 μg/(L·h). His captopril challenge test suggested that his aldosterone le-vels were suppressed by 8% (<30%) and the adrenal enhanced computed tomography scan revealed a left adrenal tumor. The patient was diagnosed with primary hyperaldosteronism (PA), aldosterone adenoma and underwent left laparoscopic adrenalectomy. Histological examination confirmed adrenal cortical adenoma. One week after the operation, his serum creatinine was increased to 127 μmol/L compared with preoperative level; eGFR was 32.34 mL/(min·1.73 m ²). His systolic blood pressure (SBP) was 110 mmHg and diastolic blood pressure (DBP) was 60 mmHg (hypotensive drugs discontinued), and serum potassium level was 5.22 mmol/L. At the end of the 2-year follow up, the serum creatinine of this patient remained at 109-158 μmol/L and eGFR fluctuated from 63.28-40.12 mL/(min·1.73 m ²). PA is one of the most common causes of secondary hypertension. Several studies have reported renal function deterioration of PA patients after unilateral adrenalectomy, like the patient in this article. Age, preoperative plasma aldosterone concentration, albuminuria and preoperative potassium level might be significant predictors of a decrease in the eGFR. Growing evidence suggests that aldosterone could contribute to structural kidney damage, arterial injury and hemodynamic disorder. At the same time, patients with PA exhibit glomerular hyperfiltration and glomerular vascular hypertension, leading to the misinterpretation of renal function in PA patients as subtle kidney damage may be masked by the glomerular hyperfiltration before treatment. After a unilateral adrenalectomy, glomerular hyperfiltration by aldosterone excess is resolved and renal damage can be unmasked. In conclusion, kidney function deterioration after adrenalectomy can be detected in some patients with PA. Thus, accurate evaluation of kidney function in patients with PA may be essential, especially for those with preoperative risk factors for postoperative renal impairment. After unilateral adrenalectomy, close monitoring of renal function and adequate management are required for PA patients.