Screening and validation of differentially expressed genes in polymyositis.

Background: Polymyositis (PM), a prevalent inflammatory myopathy, currently lacks defined pathogenic mechanism. To illuminate its pathogenesis, we integrated bioinformatics and clinical specimens to examine potential aberrant gene expression patterns and their localization. Methods: We obtained GSE128470 and GSE3112 dataset from the Gene Expression Omnibus, performed Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis using CiberSort, identified differentially expressed genes with Limma, conducted functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, constructed a Protein-Protein Interaction network, and identified hub genes using Cytoscape. ROC analysis evaluated hub gene diagnostic accuracy for PM, validated their expression levels with clinical specimens. Results: DEG analysis revealed 51 upregulated and 779 downregulated genes. Gene Ontology (GO) analysis implicated Type I interferon (IFN-Ⅰ) signaling, while KEGG pointed to cell adhesion molecule activation and oxidative phosphorylation inhibition. Protein-Protein Interaction (PPI) analysis identified 8 diagnosffftic hub genes. Clinical samples confirmed their upregulation in PM, especially IRF1 and IRF9 between muscle fibers. Different immune cell infiltrations were observed in PM patients versus controls. Conclusions: Our study explores potential pathogenic factors, diagnostic markers, and immune cells in PM, with a focus on verifying IRF1 and IRF9 upregulation in the IFN-I signaling pathway. These findings bear significance for PM diagnosis and treatment.

Risk factors of pulmonary arterial hypertension in patients with systemic lupus erythematosus.

OBJECTIVES: Pulmonary arterial hypertension symptoms in systemic lupus erythematosus patients are non-specific and early diagnosis and intervention are challenging. It remains essential to explore risk factors for pulmonary arterial hypertension in systemic lupus erythematosus patients to identify high risk patients and allow intensive monitoring. METHODS: From January 2010 to December 2018, 84 patients with systemic lupus erythematosus and pulmonary arterial hypertension and 160 patients with systemic lupus erythematosus but without pulmonary arterial hypertension were enrolled. Clinical manifestations and laboratory test results were compared between the two groups to identify predictors of pulmonary arterial hypertension. Candidate pulmonary arterial hypertension risk factors were further compared among systemic lupus erythematosus-pulmonary arterial hypertension patients with different characteristics. RESULTS: Among collected patient characteristics, Raynaud's phenomenon (OR 2.32, 95% CI: 1.17-4.61), digital vasculitis (OR 4.12, 95% CI: 1.48-11.49), pericardial effusion, pulmonary interstitial lesions, positive anti-u1 ribonucleoprotein antibodies, and positive anticardiolipin antibodies immunoglobulin G were associated with significantly higher risk of pulmonary arterial hypertension in systemic lupus erythematosus patients. Among these candidate risk factors, positive anti-u1 ribonucleoprotein antibody was independently associated with severe pulmonary arterial hypertension and more active disease. Digital vasculitis was independently associated with systemic lupus erythematosus alleviation, while pericardial effusion was associated with systemic lupus erythematosus deterioration. Pericardial effusion was associated with longer pulmonary arterial hypertension duration. CONCLUSION: The significant association between studied clinical and laboratory indicators and risk of pulmonary arterial hypertension, pulmonary arterial hypertension and systemic lupus erythematosus characteristics suggested that these factors can be used to identify patients at higher risk of pulmonary arterial hypertension and adverse outcomes. Close monitoring may be indicated in patients with these risk factors, especially with more than one risk factor.

The effects of oral treatment for systemic sclerosis related pulmonary arterial hypertension: A systematic review and meta-analysis.

OBJECTIVES: The usage of oral therapies, endothelin receptor antagonists (ERAs), phosphodiesterase type-5 (PDE-5) inhibitors and prostaglandin analogs has resulted in improved outcomes in patients with pulmonary arterial hypertension related to systemic sclerosis (SSc-PAH). However, the optimal therapeutics have not been determined. METHODS: A systematic searching in the databases of Medline (PubMed), Embase, the Cochrane Library (Central) and unpublished clinical trials (clinicaltrials.gov) was conducted to identify the clinical studies with oral treatment for SSc-PAH patients published before 1 June 2019. The data were extracted and the quality was assessed. The main outcomes are exercise capacity and hemodynamic parameters, which were synthesized and analyzed. RESULTS: In total, 27 clinical trials were enrolled for further analysis. It was demonstrated that bosentan treatment, the widely used drug for PAH, might improve the exercise capacity and pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in this clinical setting, although without significant difference. Meanwhile, the usage of prostaglandin analogs could improve the parameters mentioned above. Furthermore, combined therapy with ambrisentan and tadalafil significantly increased the treatment efficacy of key parameters in SSc-PAH patients compared with basic treatment. CONCLUSION: This meta-analysis reveals that combination therapy might provide more benefits to exercise capacity and hemodynamic parameters in SSc-PAH patients. Still more RCTs are needed to provide more solid evidence.

Diagnostic value of secreted frizzled-related protein 2 gene promoter hypermethylation in stool for colorectal cancer: A meta-analysis.

OBJECTIVE: To evaluate the diagnostic value of secreted frizzled-related protein 2 (SFRP2) gene promoter hypermethylation in stool for colorectal cancer (CRC). MATERIALS AND METHODS: Open published diagnostic study of SFRP2 gene promoter hypermethylation in stool for CRC detection was electronic searched in the databases of PubMed, EMBASE, Cochrane Library, Web of Science, and China National Knowledge Infrastructure. The data of true positive, false positive false negative, and true negative identified by stool SFRP2 gene hypermethylation was extracted and pooled for diagnostic sensitivity, specificity, and summary receiver operating characteristic (SROC) curve. RESULTS: According to the inclusion and exclusion criteria, we finally included nine publications with 792 cases in the meta-analysis. Thus, the diagnostic sensitivity was aggregated through random effect model. The pooled sensitivity was 0.82 with the corresponding 95% confidence interval (95% CI) of 0.79-0.85; the pooled specificity and its corresponding 95% CI were 0.47 and 0.40-0.53 by the random effect model; we pooled the SROC curve by sensitivity versus specificity according to data published in the nine studies. The area under the SROC curve was 0.70 (95% CI: 0.65-0.73). CONCLUSION: SFRP2 gene promoter hypermethylation in stool can was a potential biomarker for CRC diagnosis with relative high sensitivity.

[Randomized control multi-center clinical study of mycophenolate mofetil and cyclophosphamide in the treatment of connective tissue disease related interstitial lung disease].

OBJECTIVE: To investigate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of connective tissue disease-related interstitial lung disease (CTD-ILD). METHODS: A total of 60 patients with CTD-ILD, confirmed by high resolution computer tomography (HRCT), were enrolled from five clinical centers from July 2010 to July 2014. In addition to the basic glucocorticoid treatment, patients received intravenous cyclophosphamide (Group A) or oral MMF (Group B) for one year. Pulmonary function was assessed at the 3, 6, 12 months. All adverse events were recorded and efficacy and safety were evaluated at the end of this trial. RESULTS: Total 60 patients were enrolled, each group had 30 patients. 5 patients withdrew voluntarily from each group, 2 and 3 patients died in group A and B, respectively. Total 45 patients completed this trial. Neither lung function, HRCT nor adverse events had differences between the two groups or within group (P>0.05). When the analysis was done among patients with forced vital capacity (FVC) ≤ 75% and forced expiratory volume in one second (FEV1)% ≤ 75%, there were significantly statistical differences in FVC and FEV1 at 6th month compared with prior treatment in group A (both P<0.05). And there were significant increase in FVC and FEV1 at 12 months in group B (both P<0.05). But there was no statistical difference between the two groups. For the patients with diffusion capacity for carbon monoxide (DLco) ≤ 65%, there were significant increase in group A at 3, 6 and 12 months (P<0.01, P<0.05, P<0.05, respectively). but no significant increase was found in patients on MMF. And there was no difference between the two groups. No statistical difference existed in survival rate between these two groups (P>0.05). CONCLUSIONS: MMF has comparative effect as cyclophosphamide in the remission or stability of lung function and HRCT manifestations of CTD-ILD patients. MMF is generally well-tolerated, but its efficacy in maintenance therapy and long-term safety remains to be clarified.

[Effect of recombinant human tumor necrosis factor receptor type II-Fc fusion protein antibody on cytokines and bone metabolism in patients with juvenile idiopathic arthritis].

OBJECTIVE: To evaluate the influence of the recombinant human type II tumor necrosis factor receptor-antibody Fc fusion protein (rhTNFR:Fc) on cytokines and bone metabolism in patients with juvenile idiopathic arthritis (JIA). METHODS: This was a prospective, non-randomized, controlled and open-label study. Thirty-one patients with JIA in active state were enrolled at our hospital from December 2006 to June 2009. The mean age was 12.7 ± 2.3 years. Exclusive criteria included infection with tuberculosis and hepatitis B etc., abnormal renal or hepatic function. Study consists of two phases. During the first phase (0-3 months), according to the economic status, all JIA patients were divided into treatment and control groups. The treatment group consisted of 18 patients (enthesitis-related arthritis, n = 15; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 1) on a regimen of rhTNFR:Fc 0.4 mg/kg, subcutaneously injected twice weekly. The control group contained 13 patients (enthesitis-related arthritis, n = 9; polyarticular-onset arthritis, n = 2; systemic-onset type, n = 2) on a regimen of MTX 10 mg × m(-2) × w(-1). Two intolerance patients were given sulfasalazine (SASP) 30-50 mg × kg(-1) × d(-1). During the second phase (3-6 months), the responding patients continued the original therapy. The rhTNFR:Fc group received a reduced dosage of 0.4 mg × kg(-1) × w(-1). All patients of both groups who became complicated with peripheral arthritis or were non-responding had the addition of SASP. Follow-up was conducted at baseline, 1 month, 3 months and 6 months. And TNF-α, MMP-3, IL-1ß, osteocalcin (BGP), ß-collagen fragment (ß-CTx), alkaline phosphatase, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP) and bone mineral density dynamic changes were examined respectively in the treatment process. RESULTS: Alkaline phosphatase and lumbar spine bone mineral density increased while TNF-α, IL-1ß, ESR and CRP decreased significantly in two groups (P < 0.05). ESR were 16 ± 8.0 mm/h vs 60 ± 38 mm/h, CRP 10 ± 7 mg/L vs 47 ± 37 mg/L and ß-CTx 2.1 ± 0.8 vs 1.1 ± 0.9 µg/L at 1 month in two groups respectively with statistic difference (P < 0.05). BGP increased and MMP-3 decreased in both groups with no statistic difference. Femur Ward's triangular area and forearm bone mineral density had no statistic difference between two groups. Interestingly, one case with bone fracture for two years has healed after a 6-month therapy of rhTNFR:Fc as proved by X-ray. CONCLUSION: Both rhTNFR:Fc and traditional DMARDs both can reduce the levels of TNF-α, IL-1ß, ESR and CRP and increase lumbar spine bone mineral density and ALP significantly. RhTNFR: Fc improves the acute phase index and bone metabolism index earlier than the traditional therapy. Thus disease and bone destruction are controlled more earlier.

The clinical experiences of Dr. CAI Gan in treating chronic constipation.

Prof. CAI Gan is an academic leader in TCM treatment of the spleen and stomach disease. He insisted that liver depression, spleen deficiency and poor nourishment of the intestines are the core of pathogenesis for chronic constipation. Therefore he often treats the disease by strengthening the spleen, relieving the depressed liver, nourishing yin and moistening the intestines. Meanwhile he attaches great importance to syndrome differentiation and comprehensive regulation and treatment. As a result, good therapeutic effects are often achieved. The authors summarized his ways for treating chronic constipation with the following 10 methods, which are introduced below.

[Clinical analysis of 79 pulmonary arterial hypertension cases from 1892 connective tissue disease patients].

OBJECTIVE: To understand the prevalence, investigate the correlation of clinical features, explore the early-stage diagnosis and treatment of pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). METHODS: All cases with pulmonary arterial hypertension in 1892 CTD patients were analyzed retrospectively. The risk factor of PAH was evaluated and the prognostic influence of different treatments and primary diseases analyzed. RESULTS: The prevalence of PAH in patients with connective tissue disease was about 4.2%(79/1892). In these patients, systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) had the highest incidence of PAH (18.18% and 12.00%) (P < 0.01). It was obviously higher than polymyositis/dermatomyositis (6.2%), systemic lupus erythematosus (4.4%), Sjogren syndrome (3.8%), rheumatoid arthritis (0.8%) and anti-phospholipid syndrome (0.5%), etc. (P < 0.01). Raynaud's phenomenon was related to a higher pulmonary arterial pressure (P < 0.01). There was a positive correlation (P < 0.01) between the presence of Raynaud's phenomenon and pulmonary arterial pressure. Abnormal lung function was a common finding. There were associations (P < 0.05) between the degree of pulmonary hypertension and IgG, anti-U1RNP antibody positive, antiphospholipid antibody positive, pericardial effusion and interstitial pneumonia. CONCLUSION: PAH is common in connective tissue disease. SSc and MCTD have the highest prevalence of PAH. The presence of Raynaud's phenomenon anti-U1RNP antibody is positively correlated with pulmonary arterial pressure. It can predict the development of PAH. It is useful to perform ultraechocardiogrphy for an early-stage diagnosis and prognostic analysis.

[Clinical analysis of patients with systemic lupus erythematosus and concomitant pulmonary hypertension].

OBJECTIVE: To investigate the clinical manifestations, diagnosis and interventions of pulmonary hypertension (PAH) in patients with systemic lupus erythematosus (SLE). METHODS: From January 2001 to December 2007, 798 SLE patients without prior diagnosis were admitted in our hospital, among whom 39 were identified to have concomitant PAH defined by echocardiography. The clinical data of the 39 cases were analyzed retrospectively. RESULTS: The incidence of PAH was 4.9% in these cohort of SLE patients. The 39 SLE patients with concomitant PAH included 5 men and 34 women with a mean age of 34-/+12 years. Positive correlations were found between the occurrence of PAH and the Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia (P < 0.05). Patients with higher scores for SLE Disease Activity Index were liable to PAH. The presence of Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia is correlated to greater severity PAH with poor prognosis. CONCLUSION: PAH is not a rare concomitant disease in SLE patients. The presence of Raynaud phenomenon, fingertip vasculitis, anti-u1RNP antibody positivity, antiphospholipid antibody positivity, pericardial effusion, and interstitial pneumonia all suggest the likeliness of PAH in SLE patients, and echocardiographic examination may help derive an early diagnosis.