Objective:To explore the repairing effect and mechanism of tangeretin in rats with spinal cord injury.Methods:The rats were divided into sham-operation group, model group and tangeretin group according to random number table, with 8 rats in each group. Except for the sham-operation group, Allen hit method was used to make rat models in the other groups. After the model was successfully established, the tangeretin group was intragastrically administered with tangeretin 50 mg/kg, and the sham-operation group and the model group were intragastrically administered with an equal volume of normal saline once a day for 14 days. On days 0, 3, 7, and 14 after modeling, the motor function recovery of rats was assessed using the Basso-Beattie-Bresnahan (BBB) score; the morphological changes of the spinal cord tissues were observed using HE staining and Nissl staining; the SOD and GSH activities and MDA, IL-1β, TNF-α, and IL-10 levels in the spinal cord tissues of rats in each group were measured using ELISA kit detection; the GFAP and Neun expressions in the spinal cord tissues were detected by immunofluorescence; the IL-1β, TNF-α, IL-10, nuclear factor E2-related factor 2 (Nrf-2), and NAD (P) H-quinone oxidoreductase 1 (NQO-1) expressions in the spinal cord tissues were detected by Western blot.Results:Compared with the model group, the BBB score increased in the tangeretin group ( P<0.05), HE staining score decreased ( P<0.05), and the number of Nissl bodies increased ( P<0.05); the level of IL-10, SOD and GSH activities increased ( P<0.05), and IL-1β, TNF-α and MDA levels decreased in the spinal cord tissue ( P<0.05); GFAP fluorescence intensity decreased ( P<0.05) and NeuN fluorescence intensity increased ( P<0.05); the relative expression of IL-1β and TNF-α decreased ( P<0.05), and the relative expressions of IL-10, Nrf-2 and NQO-1 protein increased ( P<0.05). Conclusions:Tangeretin can exert anti-inflammatory and anti-oxidative stress effects through the Nrf2/NQO1 signaling pathway and alleviate early spinal cord injury in rats. On the other hand, it may promote the recovery of spinal cord injury by reducing glial scar generation and promoting neural cellogenesis.

OBJECTIVES: Malignant melanoma is a highly malignant and heterogeneous skin cancer. Although immunotherapy has improved survival rates, the inhibitory effect of tumor microenvironment has weakened its efficacy. To improve survival and treatment strategies, we need to develop immune-related prognostic models. Based on the analysis of the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Sequence Read Archive (SRA) database, this study aims to establish an immune-related prognosis prediction model, and to evaluate the tumor immune microenvironment by risk score to guide immunotherapy. METHODS: Skin cutaneous melanoma (SKCM) transcriptome sequencing data and corresponding clinical information were obtained from the TCGA database, differentially expressed genes were analyzed, and prognostic models were developed using univariate Cox regression, the LASSO method, and stepwise regression. Differentially expressed genes in prognostic models confirmed by real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Survival analysis was performed by using the Kaplan-Meier method, and the effect of the model was evaluated by time-dependent receiver operating characteristic curve as well as multivariate Cox regression, and the prognostic model was validated by 2 GEO melanoma datasets. Furthermore, correlations between risk score and immune cell infiltration, Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) score, immune checkpoint mRNA expression levels, tumor immune cycle, or tumor immune micro-environmental pathways were analyzed. Finally, we performed association analysis for risk score and the efficacy of immunotherapy. RESULTS: We identified 4 genes that were differentially expressed in TCGA-SKCM datasets, which were mainly associated with the tumor immune microenvironment. A prognostic model was also established based on 4 genes. Among 4 genes, the mRNA and protein levels of killer cell lectin like receptor D1 (KLRD1), leukemia inhibitory factor (LIF), and cellular retinoic acid binding protein 2 (CRABP2) genes in melanoma tissues differed significantly from those in normal skin (all P<0.01). The prognostic model was a good predictor of prognosis for patients with SKCM. The patients with high-risk scores had significantly shorter overall survival than those with low-risk scores, and consistent results were achieved in the training cohort and multiple validation cohorts (P<0.001). The risk score was strongly associated with immune cell infiltration, ESTIMATE score, immune checkpoint mRNA expression levels, tumor immune cycle, and tumor immune microenvironmental pathways (P<0.001). The correlation analysis showed that patients with the high-risk scores were in an inhibitory immune microenvironment based on the prognostic model (P<0.01). CONCLUSIONS The immune-related SKCM prognostic model constructed in this study can effectively predict the prognosis of SKCM patients. Considering its close correlation to the tumor immune microenvironment, the model has some reference value for clinical immunotherapy of SKCM.
Humans ; Melanoma/genetics* ; Skin Neoplasms/genetics* ; Tumor Microenvironment ; Prognosis

Ankylosing spondylitis (AS) is a chronic inflammatory disease mainly affecting the sacroiliac joints, spine and peripheral joints. In China, standardized diagnosis and treatment of AS is still to be popularized. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed standardization of diagnosis and treatment of AS. The purposes are: (1) to standardize the diagnosis and evaluation of AS; (2) to promote rational use of non-steroidal anti-inflammatory drugs, biological as well as traditional disease modifying anti-rheumatic drugs, so as to improve the patient′s quality of life.

To investigate the relationship between serum C-reactive protein (CRP) levels and work impairment in patients with ankylosing spondylitis (AS) based on real-world evidence. Outpatients with confirmed AS at Chinese PLA General Hospital were recruited consecutively by Smart-phone SpondyloArthritis Management System (SpAMS) from April 2016 to April 2018. The relationship between CRP and work productivity and activity impairment questionnaire (WPAI) were evaluated. Five hundred and fifty-one outpatients with AS in paid employment were recruited. The presenteeism, overall work impairment, and activity impairment rates increased by 1.4% (1.1%, 1.8%), 1.1% (0.5%, 1.6%), and 1.7% (1.3%, 2.1%), respectively, for every 10 mg/L increase in the CRP level (all P value<0.01). However, the CRP level was not associated with absenteeism after adjusting for covariates [0.5%(-0.4%, 1.0%), P>0.05]. There is a significant association between increased serum CRP levels at baseline and the previous 7-day work impairment in patients with AS. Higher CRP levels contribute to worse presenteeism, overall work impairment, and activity impairment rates, which suggests the necessity of monitoring CRP on treatment, and also indicates that anti-inflammatory therapy may be effective for improving work productivity.

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.
Antirheumatic Agents/adverse effects* ; Arthritis, Rheumatoid/drug therapy* ; Humans ; Network Meta-Analysis ; Pharmaceutical Preparations ; Randomized Controlled Trials as Topic ; Tuberculosis/drug therapy*

To investigate the predictive value of [ 18F]fluorodeoxyglucose-positron emission computed tomography(PET)/CT for disease progression in patients with dermatomyositis (DM) and interstitial lung diseases (ILD). Sixty-seven DM patients who underwent [ 18F] FDG-PET/CT imaging were retrospectively analyzed from January 2012 to September 2017 at PLA General Hospital. Their clinical manifestations and imaging characteristics were recorded. Compared with those chronically progressed (C-ILD), patients with rapid progression (RP-ILD) had significantly higher erythrocyte sedimentation rate (ESR) and standardized uptake value (SUV) in lungs ( P<0.05). In patients with RP-ILD, SUV in lungs was positively correlated with age, disease course, and ESR. Receiver operating characteristic curve analysis suggested that when lung SUV cut off value was 2.25, the sensitivity and specificity to predict disease progression was 77.8% and 72.8%, respectively. Old age, longer disease course, low creatine kinase level, higher ESR, and high SUV are prognostic factors for DM-associated ILD.

Objective: To analyze the clinical characteristics of patients with ankylosing spondylitis (AS) with inflammation bowel disease (IBD). Methods: AS patients fulfilling the 1984 modified New York diagnostic criteria were recruited in Chinese AS Prospective Imaging Cohort (CASPIC) consecutively from April 2016 to June 2017 in Chinese People′s Liberation Army General Hospital by using smart management system for spondyloarthritis (SpAMS). The diagnosis of IBD was confirmed by tissue pathology via ileocolonoscopy. Demographic, clinical and biochemical data were collected. Results: In total, 893 patients with AS were recruited with the mean age 30.8 years. The majority were men (739, 82.8%). There were 64 (7.2%) patients concomitant with IBD. The mean age [(34.5±7.5) years vs. (30.5±8.8) years, P<0.001] was older and the disease duration [(10.8±6.9) years vs. (8.1±5.9) years, P=0.001] was longer in patients with IBD than patients without. Compared with patients without IBD, patients with IBD had more frequent involvement of the cervical spine [(21.9% (14/64) vs. 10.5% (87/829), P=0.006) and thoracic spine [29.7% (19/64) vs. 12.3% (102/829), P<0.001]. Uveitis [28.1% (18/64) vs. 16.4% (136/829), P=0.017] and psoriasis [7.8% (5/64) vs. 2.3% (19/829), P=0.009] were also more common in patients concomitant with IBD. In addition, patients with IBD had significantly higher scores in BASDAI (3.3±2.1 vs. 2.4±1.8, P<0.001), BASFI [2.2 (1.0,3.3) vs. 1.1(0.2,2.4), P<0.001)] and ASAS HI (7.1±4.3 vs. 5.3±3.7, P= 0.001) than patients without IBD. Conclusions Compared with patients without IBD, AS patients concomitant with IBD have more severe disease activity and organ dysfunction. Furthermore, the uveitis and psoriasis are more frequently accompanied in AS patients with IBD.

Objective:To investigate the cause of missed diagnosis by transthoracic echocardiography (TTE) based on the characteristics of partial anomalous pulmonary venous connection (PAPVC), and to improve the ultrasonic diagnostic accuracy of PAPVC in children.Methods:The TTE results of 252 children under 12 years old who were confirmed with PAPVC at Guangdong Provincial People′s Hospital from January 2011 to June 2019 were reviewed retrospectively.The types of PAPVC and the associated atrial septal defects (ASD) as well as the confirmed and missed cases by TTE were analyzed.Results:PAPVC was right-sided in 238 patients (94.4%), left-sided in 8 patients (3.2%), and bilateral in 6 patients (2.4%). There were 177 cases (70.2%) whose pulmonary veins were abnorma-lly connected to the right atrium(RA), 37 cases (14.7%) to the junction of the RA and the superior vena cava (SVC), 27 cases (10.7%) to the distal SVC, and 6 cases (2.4%) to the inferior vena cava.Besides, pulmonary veins of 5 cases (2.0%) flew back to the RA through the coronary sinus.One hundred and ninety PAPVC cases were combined with sinus venous defects (SVD) and 53 cases combined with secondum ASD.Two hundred and twenty-one cases were accurately diagnosed while 31 cases were underestimated by TTE.The omission diagnostic rates of right superior pulmonary veins connecting to the distal SVC, 1 or 2 right pulmonary veins connecting to the RA or the junction of the RA and SVC, and left-sided PAPVC were 8 out of 18 (44.4%), 22 out of 215 (10.2%) and 1 out of 8 (12.5%), respectively.Among 54 cases with right superior pulmonary veins anomalously connected to the RA or the junction of the RA and SVC, 88.9% of them (48/54 cases) were combined with superior SVD.Among 161 cases with the right inferior pulmonary veins or 2 right pulmonary veins connected to the RA, 78.2% of them (126/161 cases) were combined with inferior SVD.There were statistically significant differences in ASD types between the 2 right-sided PAPVC groups.Conclusions:SVD is often associated with 1 or 2 right pulmonary veins connected to the RA or the junction of the RA and SVC.The cases with right superior pulmonary veins connected to the distal SVC are prone to be underestimated by TTE.Whether there is abnormal blood flowing into SVC should be noticed during superior sternal fossa examinations.Each pulmonary vein should be examined in detail in the TTE test and accurate diagnosis of PAPVC can be made in most cases.

Overexpression of exogenous lineage-determining factors succeeds in directly reprogramming fibroblasts to various cell types. Several studies have reported reprogramming of fibroblasts into induced cardiac progenitor cells (iCPCs). CRISPR/Cas9-mediated gene activation is a potential approach for cellular reprogramming due to its high precision and multiplexing capacity. Here we show lineage reprogramming to iCPCs through a dead Cas9 (dCas9)-based transcription activation system. Targeted and robust activation of endogenous cardiac factors, including GATA4, HAND2, MEF2C and TBX5 (G, H, M and T; GHMT), can reprogram human fibroblasts toward iCPCs. The iCPCs show potentials to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells . Addition of MEIS1 to GHMT induces cell cycle arrest in G2/M and facilitates cardiac reprogramming. Lineage reprogramming of human fibroblasts into iCPCs provides a promising cellular resource for disease modeling, drug discovery and individualized cardiac cell therapy.

OBJECTIVES: Contrast-induced acute kidney injury (CI-AKI) is the third cause of hospital-acquired AKI, and existing clinical prevention and treatment measures such as hydration therapy and/or administration of antioxidants N-acetylcysteine treatment and other treatments still show little effect on the prevention and treatment of CI-AKI. This study aims to explore the effect of Danhong injection on prevention of CI-AKI. METHODS: A total of 12 867 patients, who received coronary angiography, percutaneous coronary intervention, enhanced CT or vascular intervention in a tertiary hospital, were enrolled for this study. Among them, 423 in the treatment group received intravenous drip of Danhong injection, and 12 444 in the control group received routine medicine. Propensity score matching was conducted to balance confounding factors between the 2 groups and then the prevention effect of Danhong injection on CI-AKI was compared between them. RESULTS: A total of 423 pairs of patients were matched successfully. The incidence of CI-AKI in the non-Danhong control group was higher than that in the Danhong treatment group (5.7% vs 2.4%). The difference between the 2 groups was statistically significant ( CONCLUSIONS The results of this study support the use of Danhong injection in the prevention of the Stage 1 of CI-AKI.
Acute Kidney Injury/prevention & control* ; Contrast Media/adverse effects* ; Drugs, Chinese Herbal ; Humans ; Injections ; Percutaneous Coronary Intervention ; Propensity Score ; Risk Factors ; Treatment Outcome