Guidelines for diagnosis and treatment of glucocorticoid-induced osteoporosis / 中华内科杂志

Glucocorticoid-induced osteoporosis (GIOP) is a skeletal disease characterized by decreased bone strength and increased fracture risk associated with long-term glucocorticoid use. GIOP is the most common secondary osteoporosis that critically affects the quality of life of patients. Currently, the incidence of GIOP in China remains high, with insufficient awareness and lack of prevention and treatment norms. Therefore, the Chinese Rheumatology Association has established this standard based on domestic and international experience, with the aim of raising awareness of prevention and treatment among clinicians, guiding the standardized diagnosis and treatment of this disease, and improving the overall prognosis of patients with GIOP.

Clinical and immunological characteristics of 88 cases of overlap myositis / 北京大学学报(医学版)

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.

Clinical and immunological characteristics of patients with anti-synthetase syndrome complicated with cardiac involvement / 北京大学学报(医学版)

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.

Clinical characteristics of crystal deposits in joints and tendons in patients with gout / 北京大学学报(医学版)

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.

Application of lymphocytes test in peripheral blood of patients with systemic sclerosis during the treatment / 北京大学学报(医学版)

OBJECTIVE@#To explore the significance of lymphocytes in systemic sclerosis (SSc), by detecting the levels of T lymphocytes, B lymphocytes and natural killer (NK) cells, and analyzing the correlation between the lymphocytes and clinical laboratory indexes.@*METHODS@#The numbers and proportion of T, CD4+T, CD8+T, B, and NK cells were detected by flow cytometry in peripheral blood of 32 SSc patients who had taken immunosuppressive drugs and 30 healthy controls (HC). The comparison of the lymphocyte subsets in SSc with them in the HC groups, and the correlation between the lymphocytes and other clinical and laboratory indicators were analyzed by the relevant statistical analysis.@*RESULTS@#Compared with the HC group, the numbers of T, CD4+T, CD8+T, and NK cells in peripheral blood of SSc group, who had taken immunosuppressive drugs, were significantly decreased (P < 0.05). More-over, the proportion of NK cells in peripheral blood of the SSc group was also significantly lower than that in the HC group (P=0.004). In addition, all the lymphocyte subsets were decreased in peripheral blood of more than 65% of the SSc patients who had taken immunosuppressive drugs. Compared with CD4+T normal group, the positivity of Raynaud's phenomenon, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) was significantly increased in CD4+T reduction group, respectively (P＝0.024, P < 0.001, P=0.018). ESR was higher in CD8+T reduction group than CD8+T normal group (P＝0.022). The prevalence of fingertip ulcer was significantly increased in B cell decrease group (P=0.019). Compared with NK cell normal group, the prevalence of fingertip ulcer was significantly increased in NK cell lower group (P=0.033), IgM was remarkablely decreased yet (P=0.049). The correlation analysis showed that ESR was negatively correlated with the counts of T lymphocytes (r＝－0.455, P＝0.009), CD4+T lymphocytes (r＝－0.416, P＝0.018), CD8+T lymphocytes (r＝－0.430, P=0.014), B cells (r＝－0.366, P＝0.039).@*CONCLUSION@#The number of CD4+T, CD8+T, B, and NK cells significantly decreased in peripheral blood of SSc patients who had used immunosuppressive drugs, some lymphocyte subsets might be related with Raynaud's phenomenon and fingertip ulcer, and reflected the disease activity by negatively correlated with ESR and CRP; the numbers of lymphocyte subsets in peripheral blood should be detected regularly in SSc patients who had taken immunosuppressive drugs.

Glucose-6-phosphate isomerase is associated with disease activity and declines in response to infliximab treatment in rheumatoid arthritis / 中华医学杂志(英文版)

BACKGROUND@#Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.@*METHODS@#Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People's Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.@*RESULTS@#Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001).@*CONCLUSION@#Serum GPI is related to disease activity and clinical response to infliximab treatment.

Expression of plasma Dickkopf-1 in patients with rheumatoid arthritis and its correlation with peripheral blood T cell subsets / 北京大学学报(医学版)

OBJECTIVE@#To detect the levels of Dickkopf-1 (DKK-1) in the plasma of patients with rheumatoid arthritis (RA), and to analyze their correlation with peripheral blood T cell subsets and clinical indicators.@*METHODS@#Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma DKK-1 levels in 32 RA patients and 20 healthy controls, and to record the various clinical manifestations and laboratory indicators of the RA patients, and flow cytometry to detect peripheral blood T cell subsets in the RA patients (Including Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T, CD8+CD161+T cells). The plasma DKK-1 levels between the two groups were ompared, and its correlation with peripheral blood T cell subsets and clinical indicators analyzed.@*RESULTS@#(1) The plasma DKK-1 concentration of the RA patients was (124.97±64.98) ng/L. The plasma DKK-1 concentration of the healthy control group was (84.95±13.74) ng/L. The plasma DKK-1 level of the RA patients was significantly higher than that of the healthy control group (P < 0.05), and the percentage of CD8+CD161+T cells in the peripheral blood of the RA patients was significantly higher than that of the healthy control group (P < 0.05). (2) The plasma DKK-1 level was positively correlated with erythrocyte sedimentation rate (r=0.406, P=0.021), DAS28 score (r=0.372, P=0.036), immunoglobulin G(r=0.362, P=0.042), immunoglobulin A(r=0.377, P=0.033); it had no correlation with age, course of disease, C-reactive protein, rheumatoid factor, anti-cyclic citrullinated peptide antibody, immunoglobulin M, complement C3, complement C4, white blood cell, neutrophil ratio. (3) The plasma DKK-1 level in the RA patients was positively correlated with the percentage of peripheral blood CD161+CD8+T cells (r=0.413, P=0.019);it had no correlation with Treg, nTreg, aTreg, sTreg, Teff, Tfh, CD4+CD161+T, CD8+T cells. (4) The percentage of CD161+CD8+T cells was negatively correlated with erythrocyte sedimentation rate (r=-0.415, P=0.004), C-reactive protein (r=-0.393, P=0.007), DAS28 score(r=-0.392, P=0.007), rheumatoid factor (r=-0.535, P < 0.001), anti-citrullinated protein antibody (r=-0.589, P < 0.001), immunoglobulin G(r=-0.368, P=0.012) immunoglobulin M (r=-0.311, P=0.035); it had no correlation with age, disease course, immunoglobulin A, complement C3, complement C4, white blood cell, and neutrophil ratio.@*CONCLUSION@#RA patients' plasma DKK-1 levels and the percentage of CD8+CD161+T cells in T cell subsets in peripheral blood increase, which may be related to the secretion of proinflammatory cytokines in patients; DKK-1 is involved in the regulation of bone homeostasis and can be used as a marker of bone destruction in RA.

Clinical features of hydronephrosis induced by retroperitoneal fibrosis: 17 cases reports / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical features and outcome of hydronephrosis induced by retroperitoneal fibrosis (RPF), and to evaluate the effect of corticosteroid based therapy combined with surgical intervention of ureteral obstruction.@*METHODS@#A total of 17 RPF patients with hydronephrosis hospitalized in Peking University International Hospital from May 2016 to December 2019 were analyzed retrospectively.@*RESULTS@#The median age was 56 (53, 65) years, the male to female ratio was 2.4 : 1, and the disease duration was 4.00 (0.83, 8.00) months. The initial symptoms included back pain (9 cases), abdominal pain (6 cases), oliguria (2 cases) and lower limb edema (3 cases). Eight patients presented left hydronephrosis, 1 right hydronephrosis and 8 bilateral hydronephrosis. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were both elevated in 13 patients (76.5%, n=17). Immunoglobin (Ig) G4 increased in 5 cases (29.4%, n=17). IgG, IgE and IgA increased in 4 cases (30.8%, n=13), 4 cases (30.8%, n=13) and 1 case (7.7%, n=13), respectively. Among 12 patients who underwent biopsy, 3 patients were diagnosed with IgG4-relate disease. The level of IgG4 in the tissues varied, 6 cases expressed less than 10 per high power field (HPF) or no expression (50.0%). Only 2 cases expressed 10-30/HPF (16.7%), and 4 cases revealed more than 30/HPF (33.3%). Among the 17 patients with ureteral obstruction, no urinary drainage procedure was needed in 4 patients who had mild ureteral obstruction, whereas, ureteral stenting was carried out in the other 13 cases before drug treatment. Time was too short to evaluate the effect of urinary drainage procedures in 4 patients. For the rest, ureterolysis had to be performed in 3 cases after failed ureteral stent insertion. Successful drain removal was accomplished in all of these 9 patients and the mean time to drain removal was (6.7±3.0) months. In addition, 10 patients had complete medical records after an average follow-up time of 5 (3-13) months. Levels of ESR, CRP, IgG4, IgG, IgE, IgA were 54.0 (36.3, 98.5) mm/h, 26.8 (8.7, 53.0) mg/L, 1.34 (0.55, 3.36) g/L, 16.3 (13.0, 21.1) g/L, 40.5 (31.4, 203.0) IU/mL, 2.51 (1.82, 3.25) g/L at baseline, which all decreased predominantly after treatment. ESR, CRP, IgG4, IgG, IgE and IgA dropped by 38.5 (23.5, 54.3) mm/h (P < 0.01), 23.0 (5.5, 52.0) mg/L (P < 0.05), 0.92 (0.40, 2.85) g/L (P < 0.01), 6.5 (1.7, 9.1) g/L (P < 0.05), 23.7 (4.8, 162.0) IU/mL (P < 0.05) and 0.77 (0.32, 1.26) g/L (P < 0.05), respectively. Size of mass measured by CT/MRI imaging became smaller significantly and hydronephrosis relieved.@*CONCLUSION@#Onset of RPF is insidious and lack of specific initial symptoms. Corticosteroid based therapy combined with surgical intervention of relieving obstruction is effective.

Clinical and immunological characteristics of myositis complicated with thromboembolism / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyse the clinical and immunological features of patients with myositis complicated with thromboembolism.@*METHODS@#We identified a cohort of 390 myositis patients diagnosed with myositis admitted to People's Hospital of Peking University from 2003 to 2019. The patients were retrospectively enrolled in this investigation. According to the outcome of the color Doppler ultrasound, CT pulmonary angiography, pulmonary ventilation and perfusion scan patients were divided into myositis with and without thromboembolism group. Demographic, clinical (heliotrope rash, Gottron's sign/papules, periungual erythema, skin ulceration, subcutaneous calcinosis, Mechanic's hands, myalgia, interstitial lung disease, pulmonary arterial hypertension), laboratory, immunological [anti-autoantibodies including melanoma differentiation associated gene 5 (anti-MDA5), anti-Mi-2, anti-transcription intermediary factor-1γ (anti-TIF-1γ, anti-nuclear matrix protein 2 (anti-NXP2), anti-small ubiquitin-like modifier activating enzyme (anti-SAE), anti-synthetase], imaging and therapeutic status data of the patients at the diagnosis of myositis with and without thromboembolism were collected and the differences in these data were analyzed. Logistic regressive analysis was used to identify the risk factors of thromboembolism.@*RESULTS@#In the retrospective study, 390 myositis patients were investigated. The mean age of onset was (49.6±13.4) years, male to female ratio was 0.31 :1. Thromboembolism was identified in 4.62% (18/390) of the myositis patients, which was lower than the published reports. Out of 18 patients with thromboembolism, 55.6% (10/18) of them were deep venous thrombosis, followed by cerebral infarction (22.2%, 4/18), pulmonary embolism (11.1%, 2/18), renal artery embolism (5.6%, 1/18) and embolism of upper extremity (5.6%, 1/18). Fifty percent of thromboembolism events occurred 6 months after the diagnosis of myositis, 38.9% of thromboembolism events occurred 6 months within the diagnosis of myositis, 11.1% of thromboembolism events occurred 6 months before the diagnosis of myositis. As compared with the myositis patients without thromboembolism, the myositis patients complicated with thromboembolism were older [(58.3±11.7) years vs. (49.3±13.4) years, P=0.006]. C-reaction protein (CRP) (12.2 mg/L vs. 4.1 mg/L, P < 0.001), ferritin (20 085.5 μg/L vs. 216.6 μg/L, P < 0.001) and D-dimer (529.0 μg/L vs. 268.0 μg/L, P=0.002) were significantly higher in thromboembolism group. Diabetes (44.4% vs. 16.4%, P=0.006), coronary heart disease (22.2% vs. 3.0%, P=0.003) and surgery (16.7% vs. 3.5%, P=0.032) were observed more common in thromboembolism group than those without thromboembolism. Activated partial thromboplastin time (APTT) (26.9 s vs. 28.7 s, P=0.049) and albumin (32.4 g/L vs. 36.5 g/L, P=0.002) was lower in thromboembolism group. The risk factors of thromboembolism in the myositis patients were low level of albumin (OR=0.831, 95%CI: 0.736-0.939, P=0.003), diabetes (OR=4.468, 95%CI: 1.382-14.448, P=0.012), and coronary heart disease (OR=22.079, 95%CI: 3.589-135.837, P=0.001) were independent significant risk factors for thromboembolism in the patients with myositis. There was no significant difference in clinical manifestations, myositis-specific antibodies or myositis-associated antibodies between the two groups.@*CONCLUSION@#Thromboembolism is a complication of myositis. Lower levels of albumin, diabetes, and coronary heart disease might be risk factors of thromboembolism in myositis patients.

Association of Semaphorin 3A with thrombocytopenia in systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To measure the level of serum Semaphorin 3A (Sema3A) and to analyze the relationship between serum Sema3A and systemic lupus erythematosus (SLE) with thrombocytopenia.@*METHODS@#The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in 170 SLE patients, 50 Sjögren's syndrome (SS) patients, 19 hypersplenism (HS) patients and 150 healthy controls (HC). Based on the presence of thrombocytopenia and whether the thrombocytopenia was in remission, the SLE patients were divided into three groups: SLE with thrombocytopenia (41 cases), SLE with thrombocytopenia remission (28 cases), and SLE without thrombocytopenia (101 cases). According to whether there was thrombocytopenia, the SS patients were divided into SS with thrombocytopenia (18 cases) and SS without thrombocytopenia (32 cases). The 28 SLE patients who underwent bone marrow aspiration biopsy were divided into two groups from the aspect of whether the bone marrow hyperplasia was normal (19 cases) or low (9 cases), as well as from the aspect of whether the maturity disturbance of megakaryocyte was positive (8 cases) or negative (20 cases). The serum Sema3A levels in SLE, SS, HS with HC were compared, meanwhile, the correlation between serum Sema3A level and platelet (PLT) in the patients with different diseases analyzed.@*RESULTS@#(1) Serum Sema3A levels in SLE were significantly lower than in HC [(3.84±2.76) μg/L vs. (6.96±2.62) μg/L, P < 0.001], serum Sema3A levels in SS were also obviously lower than in HC [(4.35±3.57) μg/L vs. (6.96±2.62) μg/L, P < 0.001], and in HS it was lower than HC at a certain extant [(5.67±2.26) μg/L vs. (6.96±2.62) μg/L, P=0.041]. (2) Serum Sema3A levels in SLE were slightly lower than in SS, but there was no significant difference [(3.84±2.76) μg/L vs. (4.35±3.57) μg/L, P=0.282]. However, when compared with HS, serum Sema3A levels in SLE were significantly lower [(3.84±2.76) μg/L vs. (5.67±2.26) μg/L, P=0.006]. (3) Serum Sema3A concentration in SLE with thrombocytopenia was significantly lower than in SLE with thrombocytopenia remission [(1.28±1.06) μg/L vs. (3.83±2.65) μg/L, P < 0.001], and in SLE patients without thrombocytopenia [(1.28±1.06) μg/L vs. (4.87±2.60) μg/L, P < 0.001]. There was no significant difference between SLE with thrombocytopenia remission and SLE without thrombocytopenia [(3.83±2.65) μg/L vs. (4.87±2.600 μg/L, P=0.123]. Serum Sema3A concentration in SLE with thrombocytopenia was slightly lower than in SS with thrombocytopenia, but there was no significant difference [(1.28±1.06) μg/L vs. (1.68±1.11) μg/L, P=0.189]. (4) Strong positive correlations were found between serum Sema3A and PLT in SLE (r=0.600, P < 0.001). Positive correlations were also found between serum Sema3A and PLT in SS (r=0.573, P < 0.001). However, there was no such correlation showed in HS patients (P=0.393). (5) There was no significant difference of serum Sema3A concentration in SLE whether the bone marrow hyperplasia was normal or low. And the same situation appeared in the patients whether the maturity disturbance of megakaryocyte was positive or negative (P>0.05).@*CONCLUSION@#Serum Sema3A was significantly reduced in SLE patients, and it was highly correlated with the blood damage. Similar conclusions could be drawn in patients with SS. The serum level of Sema3A was generally decreasing in desmosis which merged thrombocytopenia, and was obviously positive correlated with platelet counts.

Cross-sectional study on clinic behavior and therapeutic status of patients with psoriatic arthritis in multi-center / 北京大学学报(医学版)

OBJECTIVE@#To investigate and analyse the features of treatment behavior and standardized therapeutic status of patients with psoriatic arthritis (PsA).@*METHODS@#Out patients diagnosed with PsA in People's Hospital of Peking University, Haidian Hospital, People's Hospital of Jianyang City, Central Hospital of Xinxiang City, Integrated Traditional Chinese and Western Medicine Hospital of Cangzhou City, The Third Hospital of Hebei Medical University from February to June 2018 were enrolled in this investigation. The data including gender, age of onset, course of disease, site of first consulting department, time of the first visit and definite diagnosis, follow-up interval, and use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and biological DMARDs (BioDMARDs) were collected and analyzed.@*RESULTS@#In the cross-sectional study, 133 PsA patients were investigated. The mean age of onset was (47±11) years, the male to female ratio was 1.3:1, and mean disease duration was (16±8) years. Rheumatology department was the most common site of first hospital visit (37.6%, 50/133). Orthopedics department and dermatological department were visited by 24.1% (32/133) and 23.3% (31/133), respectively. Ratio of definite diagnosis was the highest in rheumatology department which was 78% (39/50). The ratio of definite diagnosis of dermatological department was the second highest, which was 19.4% (6/31). The mean definite diagnosed time was 7.6 months since the first visit of PsA patients, and diagnosed time was the shortest in rheumatology department, which had statistical significance. 37% PsA patients were treated appropriately in 3 months, 17.3% PsA patients were treated in 3-6 months and 40.2% patients with PsA visited their doctor more than once a year. 48.8% patients hadn't received standardized treatment before visit, and one third patients never received the therapy of DMARDs. Methotrexate was the most commonly used cDMARDs (58.3%), followed by leflunomide (20.5%) and BioDMARDs (19.7%), and biologicals were tumor necrosis factor antagonists.@*CONCLUSION@#In this multi-center study, the first visit department of PsA patients was widely distributed, and most patients were definitely diagnosed in Rheumatology Department. The time of their first visit and definite diagnosis were delayed due to multi factors. Nearly half of the patients did not receive standardized treatment.

Ginsenoside CK induces apoptosis of human liver cancer SMMC-7721 cells through inhibition of TGF-β1/Smads signaling pathway / 药学学报

This study aimed to investigate apoptosis induction of ginsenoside compound K (ginsenoside CK) in human liver cancer SMMC-7721 cells and the involvement of TGF-β1/Smads signaling pathway. MTT assay was used to detect cell viability following ginsenoside CK treatment in SMMC-7721 cells. Annexin V-FITC/PI assay was used to detect apoptosis. After ginsenoside CK, or TGF-β1/Smads pathway activator TGFβ1 and inhibitor LY2109761 treatment, the TGF-β1/Smads pathway proteins and apoptosis proteins were detected by Western blot. The results showed that ginsenoside CK inhibited the proliferation of SMMC-7721 cells in a dose- and time-dependent manner. Annexin V-FITC/PI showed that ginsenoside CK induced apoptosis in SMMC-7721 cells. Meanwhile, ginsenoside CK inhibited the expression of Smad2/3, p-Smad2/3, Smad4, but promoted Smad7 expression, cleavage of caspase-3 and down-regulated Bcl-2/Bax. Compared with TGFβ1 treatment alone, levels of Smad2/3, p-Smad2/3, Smad4 and the ratio of Bcl-2/Bax were down-regulated, whereas Smad7 or cleaved caspase-3 was up-regulated in the ginsenoside CK+TGF-β1 group. In addition, Smad2/3, p-Smad2/3 and Smad4 expression were decreased in LY2109761 group. Compared with LY2109761 group, cleaved caspase-3 expression and Bcl-2/Bax have no significant change in ginsenoside CK+LY2109761 group. Taken together, our results showed that ginsenoside CK induced apoptosis in SMMC-7721 cells, and such induction is related to inhibiting TGF-β1/Smads signaling pathway.

Increased serum soluble-endoglin level and its clinical significance in antiphospholipid syndrome / 北京大学学报(医学版)

OBJECTIVE@#To detect the serum levels of soluble endothelial glycoprotein endoglin (s-Eng) in patients with antiphospholipid syndrome (APS) and to evaluate the correlation between s-Eng levels and clinical features and laboratory parameters.@*METHODS@#The levels of serum s-Eng were measured by enzyme linked immunosorbent assay (ELISA) in 139 patients with APS, 44 patients with SLE but no APS, 37 patients with primary Sjögren's syndrome (pSS), 23 patients with Bechet's disease (BD), 22 patients with systemic sclerosis (SSc) and 22 persistent anticardiolipin antibody (aCL) positive individuals without SLE or APS (simply aCL positive group) and 87 health controls (HC) without any auto-immune diseases. These APS patients included 64 primary APS patients and 75 APS patients secondary to SLE.The correlation between the clinical data, laboratory parameters, and serum s-Eng levels were analyzed.Independent samples t test, paired t test, Chi-square Test, Mann-Whitney U test, Pearson's χ2 test were used for statistical analyses.@*RESULTS@#(1) The serum levels of s-Eng were significantly higher in the patients with APS whether primary or secondary to SLE than in the health controls and simply aCL positive group and the patients with other autoimmune diseases, including SLE, pSS, BD and SSc (P<0.001). There was no significant difference in the serum s-Eng levels between simply aCL positive group and health controls [(5.17±2.00) mg/L vs. (5.04±1.11) mg/L, P>0.05]. (2) The best cut-off value for the diagnosis of APS was no less than 8.37 mg/L as mean ± 3SD value, with the sensitivity at 0.772 and the specificity at 0.928. The Youden index was 0.700. These results indicated good validity of s-Eng as a diagnostic marker for APS. (3) The proportions of artery thrombosis and pathological pregnancy were higher in the group of s-Eng-positive APS patients than that in s-Eng-negative group (46/81 vs. 19/58, 29/65 vs. 10/44, respectively, all P<0.05). The levels of PLT were lower in the group of s-Eng-positive APS patients (72.00×109/L vs. 119.00×109/L, P<0.001). (4) The proportions of the presence (93.83% vs. 37.93%, P<0.001) and titer (61.70 U/mL vs. 15.45 U/mL, P<0.001) of aCL were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group. The proportions of the presence (61.73% vs. 43.10%, P<0.05) and titer (33.48 U/mL vs.17.40 U/mL, P<0.05) of anti-β2-glycoprotein I antibody were both higher in the group of s-Eng-positive APS patients than in s-Eng-negative group too.@*CONCLUSION@#s-Eng serum levels were significantly increased in the patients with APS, and it may play a role as acomplementary serological marker for the diagnosis and risk prediction of APS.

Study of bone mineral density and serum bone turnover markers in newly diagnosed systemic lupus erythematosus patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the changes of bone mineral density (BMD) and serum bone turnover factor in newly diagnosed systemic lupus erythematous (SLE) patients.@*METHODS@#Eighty newly diagnosed SLE patients and 80 age and gender matched healthy controls were enrolled. None of the SLE patients had ever received glucocorticoid, immunosuppressive agents or vitamin D. BMD was measured at radius,lumbar spine and hip by dual X ray absorptiometry (DXA). Bone turnover markers including serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b),bone alkaline phosphatase (BAP) and 25-hydroxy vitamin D3 (25-OH-VD3) were measured by enzyme-linked immunosorbent assay (ELISA). Logistic regression was employed to analyze the risk factors associated with decreased BMD.@*RESULTS@#Mean age of the SLE patients was (32.8±12.4) years, and 85% were female, none of whom were post-menopausal. BMD was significantly reduced in all the measured sites, compared with the healthy controls. Sixteen (20%) of the patients were osteopenic in at least one site measured locations. The serum levels of 25-OH-VD3 were markedly reduced in the newly diagnosed SLE patients than those of the normal controls [(46.1+12.3) nmol/L vs. (25.4+11.2) nmol/L, P<0.001)]. The serum levels of 25-OH-VD3 in the SLE patients with nephritis were much lower than those without nephritis (P=0.04). A significant negative correlation was demonstrated between the serum concentration of 25-OH-VD3 and the disease activity scores as measured by SLE disease activity index (SLEDAI) (r=-0.3,P=0.001). The serum TRAP5b concentration was positively correlated with SLEDAI (r=0.435,P=0.003). Age (P=0.058) and SLEDAI (P=0.085) were probably associated with decreased BMD in Logistic regression analysis.@*CONCLUSION@#The study showed reduced BMD in untreated SLE patients. The role of chronic inflammation was of probable importance in bone metabolism.

Clinical significance of detection of soluble interleukin 2 receptor alpha chain in the assessment of rheumatoid arthritis disease activity / 北京大学学报(医学版)

OBJECTIVE@#To evaluate soluble interleukin-2 receptor alpha chain (sIL-2Rα, sCD25) in serum for the determination of rheumatoid arthritis (RA) activity.@*METHODS@#Peripheral blood was collected from 108 patients with RA, 39 patients with osteoarthritis (OA) and 50 healthy control subjects, and synovial fluids were from 40 patients with RA. The sera from the patients with RA, the disease control group (osteoarthritis), the healthy control group, and the synovial fluids of the RA patients were detected by enzyme-linked immunosorbent assay (ELISA).The clinical manifestations and laboratory parameters of the patients with RA were recorded and the correlation with the serum sCD25 level was analyzed.@*RESULTS@#The serum sCD25 concentration in RA group was (2 886±1 333) ng/L, the serum sCD25 concentration in OA group was (2 090±718) ng/L, and the serum sCD25 concentration in healthy group was (1 768±753) ng/L. The serum sCD25 level in the patients with RA was significantly higher than that in the disease controls and healthy controls (P<0.001). Sensitivity of serum sCD25 in the diagnosis of RA was 66.1% and specificity was 83.0%;serum sCD25 levels and erythrocyte sedimentation rate (r=0.321, P=0.001), C-reactive protein (r=0.446, P<0.001), DAS28 score (r=0.324, P<0.001), joint tenderness count (r=0.203, P=0.024), D-dimer levels (r=0.383, P<0.001), age (r=0.24, P=0.007), IgG (r=0.207, P=0.028), HRF-IgG (r=0.345, P=0.034) showed a significant positive correlation, and disease duration (r=-0.206, P=0.021) showed a negative correlation with sCD25;In patients with rheumatoid arthritis, the positive rates of serum ESR, CRP, and sCD25 were 14.3% (2 cases), 14.3% (2 cases), and 71.4% (10 cases) in the low disease activity group. The positive rates of serum ESR, CRP and sCD25 in the moderate disease activity group were 94.2% (49 cases), 82.7% (43 cases), and 86.5% (45 cases). The positive rates of serum ESR, CRP, and sCD25 in the high disease activity group were 100% (42 cases), 95.2% (40 cases), and 90.5% (38 cases);36 cases of ESR and/or CRP were negative (about 33.3%) in 108 patients, serum sCD5 levels of 17 cases in these 36 cases (about 47.2%)increased, of which 14 cases (about 82.4%) had a DAS28 score higher than 3.2.@*CONCLUSION@#The serum sCD25 has a high specificity for diagnosis of RA and a poor sensitivity. The serum level is closely related to the activity of RA, indicating that sCD25 may be involved in the inflammatory process of RA and may become a new inflammatory marker of RA. It is more meaningful for detection of serum sCD25 when RA is active, but ESR and/or CRP is negative.

Anti-inflammatory effect of TTF1-NP on lipopoiysaccharide stimulated human hepatocellular carcinoma cells / 药学学报

The study was designed to test the role of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle (TTF1-NP) on lipopoiysaccharide (LPS)-induced inflammatory response, and to explore the anti-inflammatory mechanism in human hepatocellular carcinoma cells. Inflammatory responses were induced in human hepato-cellular carcinoma HepG2 cells with LPS; Proliferation effect of TTF1-NP in LPS-stimulated HepG2 cells were detected by MTT assay; The expression of TLR4, AKT/mTOR signaling related proteins and IL-6 were detected by Western blot assay. The results showed that TTF1-NP inhibited the proliferation of HepG2 cells induced by LPS in a dose-dependent manner; TTF1-NP inhibited the expression of TLR4, the activation of AKT and mTOR, and expression of IL-6 in a dose-dependent manner; TTF1-NP inhibited the activation of AKT/mTOR signaling pathway and TLR4 proteins leading to suppression of IL-6 expression in HepG2 cells stimulated by insulin. These results suggest that TTF1-NP inhibited inflammatory responses from LPS treatment with a potential mechanisms in the inhibition of AKT/mTOR pathway.

Apoptosis of human hepatocellular carcinoma HepG-2 cells upon inhibition of STAT3 by 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle / 药学学报

This study was designed to investigate the mechanism of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle (TTF1-NP) in the induction of apoptosis of human hepatocellular carcinoma HepG-2 cells. MTT assay, immunocytochemical staining and flow cytometry with Annexin V-FITC/PI were used to demonstrate inhibition of proliferation of HepG-2 cells and cell apoptosis. The inhibition was studied in a dose- and time-dependent manner. Western blot results showed that TTF1-NP down-regulated the signals of survivin, p-STAT3 and STAT3, but up-regulated the expression level of cleaved caspase-3. Taken together, our results showed that TTF1-NP induced HepG-2 cell apoptosis through inhibition of the STAT3 expression.

Mechanism of TTF1-NP induced implanted hepatoma tumor apoptosis in nude mice by endoplasmic reticulum stress pathway / 药学学报

This study was designed to investigate the effect of 5,2',4'-trihydroxy-6,7,5'-trimethoxy flavone nanoparticle (TTF1-NP) on inducing apoptosis of implanted tumour cells in nude mice and the mechanism of endoplasmic reticulum stress pathway. The implanted hepatoma model was established in nude mice, and used to test the drug TTF1-NP in five groups (vehicle, 5 μmol·kg-1 TTF1-NP, 10 μmol·kg-1 TTF1-NP, 20 μmol·kg-1 TTF1-NP and adriamycin). The nude mice were killed after the treatment to determine the tumor growth inhibition rate (IR). Morphological changes of implanted tumor cells were observed by HE staining; apoptosis of tumor cells was detected by TUNEL; the protein expression of GRP78, p-JNK and caspase 12 were analyzed using immunocytochemistry staining and Western blotting. We tested the effects of TTF1-NP on implanted HepG-2 cell tumor growth in nude mice. TTF1-NP-treated mice showed volume of tumor smaller than that of the vehicle-treated mice. The tumor mass of the TTF1-NP-treated mice were significantly reduced than those of the vehicle-treated mice. In addition, the tumor growth rate of the TTF1-NP-treated mice was significantly lower than that of the vehicle-treated mice, and the tumor growth inhibition ratio of the TTF1-NP-treated mice was significantly higher than that of the vehicle-treated mice. TTF1-NP exhibited an inhibitory effect on implanted tumor cells in the model. The IR was 51.2%, 54.2%, 61.8% and 65.9%, respectively. In comparison with the vehicle group, the treated groups exhibited alteration in cell morphology and apoptosis of tumor cells, and expression of GRP78, p-JNK and caspase 12, which were observed by immunocytochemistry staining and Western blotting. Taken together, our results suggest that TTF1-NP induces apoptosis of implanted tumor cells in nude mice and the main mechanism is related to activation of endoplasmic reticulum stress.

Taxonomy and Application of Micromonospora / 微生物学通报

Micromonospora distributes extensively in environment. But most of them have not been known because the limitation of isolation and taxonomic approach. The phenotypic information such as morphological, cultural and physiological characteristics have been applied widely in the taxonomy of Micromonospora. The functions of molecular methods become more and more important in the taxonomy of Micromonospra accompanying with the development of the polyphasic taxonomy. Micromonospora is one of the most important sources in finding new bioactive compounds, some of them can yield antibiotics, such as gentamicins, rafomicins and newmicins, some of them can degrade natural rubber and fibrin. It indicated in recent years’ study that some bioactive compounds with particular chemical construction could be found from Micromonospora. These compounds can identify cancer cells and kill them effectively.