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Objective:To investigate the clinical features and treatment status of immune-related myositis (IRM) caused by immune checkpoint inhibitors (ICIs) in order to improve the diagnosis and treatment rate of the disease.Methods:Two cases of IRM combined with the diagnosis and treatment were described and the literature about IRM in the past 10 years was reviewed, and the clinical data of 59 patients were analyzed.Results:IRM was more common in males, with a total of 47 (79.7%). IRM usually occurred after 45 days of medication or after two doses. The clinical manifestations were mainly myalgia and muscle weakness, which were more common in the limbs. The initial symptoms were ptosis and diplopia. Fifty patients (84.7%) had serum creatine kinase (CK) levels higher than twice the upper limit of normal (UNL). In immunological examinations, 18 patients were found to be positive for anti-rhabdoid muscle antibody (AsM-Ab), while most of the myositisspecific antibodies (MSAs) and myositis-associated antibodies (MAAs) were negative. Thirty-four patients (75.6%) had abnormal EMG, and most patients showed myogenic injury. Muscle magnetic resonance imaging (MRI) showed muscle edema and inflammation in 8 patients. Muscle biopsies from 18 (45.0%) patients showed varying degrees of necrotic myofibers. Fifty-seven patients (96.6%) discontinued ICIs after developing IRM, 54(91.5%) received cortico-steroids, and 20(33.9%) received other treatments including intravenous immuno-globulin (IVIG), plasma exchange.Conclusion:IRM can occur in the early stage of ICIs treatment. Electro-myography, muscle MRI and muscle biopsy in suspicious cases can improve the diagnosis rate of the disease. Early use of corticoteroid, IVIG and other immunotherapy can effectively alleviate the disease.
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Objective:To analyze the efficacy and safety of curcumin in the treatment of knee osteoarthritis.Methods:The randomized controlled trials of curcumin in the treatment of knee osteoarthritis published from January 2011 to August 2021 were retrieved. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the efficacy related indexes and the incidence of adverse events were analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference of efficacy indexes, the odds ratio ( OR) was calculated for the difference of safety indexes, the difference was compared by t test. Results:① A total of 9 relevant literatures were included, all of which were in English. ② A total of 724 patients were included in the study, of which 383 were treated with curcumin capsules and 341 were treated with placebo. ③ The visual analogue scale/score (VAS) of patients treated with oral curcumin at 3-4, 6 and 8 weeks were significantly lower than those of patients treated with oral placebo, the differences were statistically significant [weighted mean difference ( WMD)=-1.09, 95% CI (-1.44, -0.73), P<0.001; WMD=-1.52, 95% CI (-2.35, -0.69), P<0.001; WMD=-1.20, 95% CI(-1.71, -0.69), P<0.001]. ④ The western Ontario and McMaster universities osteoarthritis index (WOMAC) scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-7.96, 95% CI(-14.89, -1.04), P=0.020; WMD=-15.34, 95% CI(-20.51, -10.18), P<0.001]. Specifically, the WOMAC pain and stiffness scores of patients treated with oral curcumin for 6-8 weeks were significantly lower than those of patients treated with oral placebo, and the differences were statistically significant [ WMD=-2.16, 95% CI(-3.69, -0.63), P=0.010; WMD=-1.00, 95% CI (-1.54, -0.46), P<0.001]. The WOMAC joint function scores of patients treated with oral curcumin for 3-4 and 6-8 weeks were significantly lower than those of patients treated with oral placebo, the difference was statistically significant [ WMD=-3.21, 95% CI(-4.51, -1.92), P<0.001; WMD=-7.07, 95% CI(-11.19, -2.94), P<0.001]. ⑤ There was no significant difference in the incidence of adverse events between oral curcumin and placebo [ OR=1.19, 95% P(0.74, 1.90), P=0.478]. Conclusion:Compared with placebo, oral curcumin can significantly alleviate the pain, stiffness and joint function of patients with knee osteoarthritis, and its safety is similar to placebo.
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Objective:To compare the clinical efficacy and safety of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis.Methods:The relevant literatures including the randomized control study of intra-articular injection of platelet rich plasma and hyaluronic acid in the treatment of knee osteoarthritis published from January 2010 to December 2021 were searched. The bias risk of the included literatures was evaluated by Revman 5.3 software, and the data were processed and analyzed by Stata 16.0 software. The weighted mean difference ( WMD) was calculated for the difference ofefficacy indexes, and the difference was compared by t-test. The odds ratio ( OR) was calculated for the difference of safety index, and the difference was compared by t-test. Results:① A total of 10 literatures were included, all of which were in English. ② A total of 921 patients were included in the study, of which 479 patients were treated with intra-articular injection of platelet rich plasma and 442 patients were treated with intra-articular injection of hyaluronic acid. ③ Comparing the VAS scores of platelet rich plasma injection and hyaluronic acid injection, the visual analogue scale (VAS) scores of platelet rich plasma injection patients were significantly lower than those of hyaluronic acid injection patients after 6 and 12 months of injection treatment, and the difference was statistically significant [ WMD(95% CI)=-0.66(-1.25, -0.77), P=0.029; WMD(95% CI)= -0.90(-1.51, -0.29), P=0.004]. ④ The specific performance was that the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score of patients injected with platelet rich plasma after 6 and 12 months of injection treatment was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-0.76(-1.06, 0.45), P<0.001; WMD(95% CI)=-1.35(-2.05, -0.65), P<0.01]; After 3, 6 and 12 months of injection treatment, the WOMAC stiffness score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [( WMD(95% CI)=-0.37(-0.66, -0.08), P=0.011; WMD(95% CI)=-0.30(-0.57, -0.04), P=0.023; WMD(95% CI)=-0.62(-0.92, -0.33), P<0.001]; After 3, 6 and 12 months of injection treatment, the WOMAC function score of patients injected with platelet rich plasma was significantly lower than that of patients injected with hyaluronic acid [ WMD(95% CI)=-1.90 (-2.53, -1.27), P<0.001; WMD(95% CI)=-5.77(-9.20, -2.34), P=0.001; WMD(95% CI)=-5.72(-8.62, -2.82), P<0.001]. ⑤There was no significant difference in the incidence of adverse events between the two intra-articular injection methods [ OR(95% CI)=1.28(0.68, 2.42), P=0.440]. Conclusion:Compared with intra-articular injection of hyaluronic acid, the short-term clinical efficacy of injection of platelet rich plasma is equivalent to that of injection of hyaluronic acid, but the long-term clinical efficacy is better, and the safety of the two methods is similiar.
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ObjectiveTo investigate the changes and potential effects of differentially expressed microRNAs (miRNAs) in the development and progression of liver injury in a mouse model of autoimmune hepatitis (AIH) induced by concanavalin A (ConA). MethodsEight healthy male specific pathogen-free C57BL/6 mice were randomly divided into model group and control group, with four mice in each group. The mice in the model group were given tail vein injection of ConA 15 mg/kg, and those in the control group were given an equal volume of normal saline. All mice were sacrificed after 8 hours of modeling, Total RNA in liver tissue was extracted, gene microarray was used to screen out differentially expressed miRNAs, and target prediction and function analysis were performed for upregulated and downregulated miRNAs. The independent samples t-test was used for comparison of differentially expressed miRNAs between two groups. ResultsThe principal component analysis showed that the inter-group difference of the data extracted by gene microarray met the conditions for further analysis. Compared with the control group, the model group had 31 upregulated miRNAs and 18 downregulated miRNAs in mouse liver, which had a regulatory relationship with 959 target genes (601 upregulated genes and 358 downregulated genes). GO analysis showed that in the model group, the target genes of the upregulated miRNAs mainly had the molecular functions such as “DNA binding” (P=1.47×10-6), participated in the biological processes such as “transcription, DNA-templated” (P=2.36×10-7), and were mainly enriched in the cellular components such as “neuronal cell body” (P=5.99×10-6), while the target genes of the downregulated miRNAs had the molecular functions such as “RNA polymerase II proximal promoter sequence-specific DNA binding” (P=2.49×10-6), participated in the biological processes such as “regulation of transcription, DNA-templated” (P=1.64×10-11), and were mainly enriched in the cellular components such as “nucleoplasm” (P=4.30×10-10). KEGG pathway enrichment analysis showed that the target genes of the upregulated miRNAs were mainly enriched in “Endocytosis” (P=0.000 4), while the target genes of the downregulated miRNAs were mainly enriched in the “Hippo signaling pathway” (P=0.004), and the above functional analysis results were statistically significant (P＜0.05). ConclusionThere are differentially expressed miRNAs in the pathogenesis of AIH, and these differentially expressed miRNAs can provide new targets for the clinical treatment of AIH.
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Objective To improve the clinical understanding of the disease by retrospective analysing 55 cases of patients with panniculitis. Methods The hospitalized patients with panniculitis were collected from December 2011 to October 2018 in the Shanxi Dayi Hospital Affiliated to Shanxi Medical University. The demographics, clinical manifestations, laboratory examinations and treatments were analyzed and summarized, rate or composition ratio were applied for statistical description of the counting data. Results The proportion of males and females in the 55 patients was 1:2.23, with an average of (53±15) years (18-82 years). A total of 52 cases of nodular panniculitis (including 14 cases of mesenteric involvement) and 3 cases of special type of panniculitis were collected. Patients with nodular panniculitis were often presented with subcutaneous nodules or masses. According to the affected parts, they cowld be divided into skin sub-type and systemic sub-type. Among them, 32 cases were skin sub-type and 20 cases are systemic sub-type. The most frequently involved organs were mesenteric and kidney involvement. Nine of 55 patients was complicated with tumor. Patients with mesenteric panniculitis mainly presented with abdominal pain and bloating, which were mainly diagnosed according to CT findings. Patients with systemic panniculitis could be significantly relieved after treatment with coricosteroids and immunosuppressive agents. Conclusion Panniculitis is an inflammatory disease of unknown etiology. It is frequent in middle-aged and elderly people. It presents with various clinical manifestations and lacks specificity. The diagnosis is mainly based on pathological results. It is easy to be complicated with tumors. When subcutaneous nodules are found, pathological examination should be performed in order to avoid misdiagnosis.
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A comparison is made on the healthcare systems,economy,informationization environment,developers,investment and compensation mechanisms in nine countries featuring early startup,rich experiences,and relatively higher ratio of success in their development projects.This lead to a discussion focusing on the construction steps and development strategies for regional health informationization,and an analysis of the present regional health informationization overseas,common measures taken,and key factors for successful regional health informationization.Based on these,recommendations were made on development of regional health informationization compliant to China's circumstances.
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By means of literature review,the paper made a comparative study of key development projects of healthcare information in China over the last decade,in terms of their project characteristics,economic environment,development entity,investment and compensation practice,development strategy,coverage,experience and promotional values.Setbacks identified include the following:discrepancy in regional development stages of healthcare information; successful pilots are limited to scientific research samples; lack of regional models; systems separation; poor continuity and coordination; waste and insufficiency of resources in the investment and construction among others.The authors recommend a better exchange of experiences in building the regional healthcare information service platforms,greater investment,better compensation mechanism,better top-tier design,and maximized coverage within reach of supervision and technology.
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Objective To investigate the role of myeloid dendritic cells(mDC)in the pathogenesis of ankylosing spondylitis (AS),and to study the mechanism of tumour necrosis factor (TNF)-α blocker on the treatment of AS by counting the number of mDC before and after the treatment.Methods Peripheral blood from 21 AS patients treated with 50 mg rhTNFR-Fc and 15 AS patients treated with placebo were investigated at week 0,week 2 and week 6 in a randomized,double-blind,placebo-controlled trial.Three-color flow cytometry analysis was used to investigate the change of the number of mDC before and after the treatment.And their correlation with the clinical parameters was analyzed.Results MHC Class Ⅰ positive mDC(Lin-/CD11c+/HLA-abc+)in AS patients was slightly less than in healthy controls (not statistically significant).No significant change in MHC Class Ⅰ mDC number was observed after drug treatment.The number of MHC Class Ⅱ mDC cells was not correlated with clinical parameters.Conclusion The treatment with rhTNFR-Fc in AS induces a significant upregnlation of MHC-Ⅱ DC.
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Objective To compare the changes of 11 cytokines in ankylosing spondylitis(AS)before and after treatment with a loading regimen of infliximab and to evaluate the potential AS related discriminating cytokines and explore their value in diseases activity evaluation and possible association with therapeutic response.Methods This was an open-labeled,phase Ⅱ clinical trial conducted in 2 medical centers.All AS patients were infused with infliximab at week 0,2,6.The dosage was 5 mg/kg.Disease activity parameters were assessed at week 0,2,6 and 10.Eleven serum cytokines were detected using protein chip technique,then,serum IL-6 level wag measured by sandwich enzyme-linked immunosorbent assay(ELISA).Results IL-6 was detected by EHSA.Compared with healthy controls.IL-6 level incregsed markediy in AS(P<0.01).After treated with infliximab,IL-6 level decreased at week 2(P<0.01)and maintained at low level until week 10.Baseline serum IL-6 level was positively associated with AS disease activity index(night pain scores、ESRand CRP)(P<0.01).Conclusion Serum IL-6 level is associated with AS disease activity and may become a useful parameter for monitoring the clinical response of infliximab in AS patients.IL-6 is an important cytokine involved in the pathogenesis of AS.
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Objective To investigate the efficacy and safety of mycophenolate mofetil (MMF) for refractory autoimmune 1iver disease:Methods Six patients with autoimmune liver disease who had failed MMF treatment and variation of biochemical indexes.adverse effects of the MMF treatment were recorded.Results After MMF treatment.the serum 1evels of alanine aminotransferase (ALT) were decreased to nOrmal level in three of four patients with higher ALT.The serum levels of alkaline phosphatase (ALP) were decreased to more than fifty percent of normal level in four of five patients with higher ALP.The serum levels of γ-glutamyhransferase (GGT) were decreased to more than fifty percent of normal level in all five patients with higher GGT.The serum levels of immunoglobulin G (IgG) and γ-globulin were decreased to normal level in all two patients who had elevated IgG and r-globulin levels.The serum levels of total bilirublin and total bile acid.the count of white blood cell and platelet had no change.There were no adverse effects in a11 six patients.Conclusion MMF treatment for early refactory autoimmune liver disease is effective with few sideeffects.
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Objective To evaluate the efficacy profile of loading dose of anti-tumour necrosis factor (TNF)-α antibody infliximab in the treatment of ankylosing spondylitis (AS) and investigate the parameters that could be used as predicting factors for clinical response to infliximab in AS.Methods This was an open-labeled.mutticenter trial.Subiects eligible for this study were adults with a diagnosis of definite AS.Active disease was a Bath AS disease activity index(BASDAI)≥4 and spinal pain VAS≥4.Infliximab 5 md/kg was infused at weeks 0,2,6.All patients were followed for up to 10 weeks.Logistic regression likelihood ratio tests (univariate and multivariate) were performed to investigate which of the following parameters assessed before treatment were associated with ASAS 20,ASAS 40 and BASDAI 50 response:sex.age.disease duration,HLA-B27,BASDAI,spinal inflammatory (questions 5 and 6 of the BASDAI),spinal pain,night pain,patient global assessment,Bath AS functional index (BASFI),BASMI,enthesis index (EI),presence of peripheral arthritis,chest expansion,ESR,CRP,Bath AS radiology index (BASRI).Results Sixty-three patients (79% were males.90% were HLA-B27 postivie with a median age of 32 years and the median disease duration was 10 years) completed the treatment.The proportion of ASAS 20 responders.ASAS 40 responders and BASDAI 50 at week 10 was 84%,75%,70%,respectively.Univariate and multivariate Logistic regression analysis showed none of the 17 parameters evaluated at week 0 including ESR/CRP,disease duration were predictive for improvement.Conclnsion In this study,a loading regimen of infliximab has demonstrated consistent efficacy and none of the demographic parameters and baseline AS activity parameters are predictors for maior clinical response to infliximab in active AS.