Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

Objective To explore the efficacy of repetitive peripheral magnetic stimulation(rPMS)in patients with lumbar disc herniation(LDH).Methods From March 2023 to March 2024,60 LDH patients were recruited in the inpatient or outpatient department of the rehabilitation department of a tertiary hospital.All patients were randomly assigned to the rPMS group or the conventional group,30 cases in each group.Both groups received routine physical therapy,and the rPMS group was treated with rPMS on this basis.VAS,JOA,and neurophysiological tests were performed before intervention and 2 weeks after intervention.Results The VAS and JOA scores of the two groups were significantly lower than those before treatment(P<0.05).Compared with the conventional group,the VAS and JOA scores of the rPMS group were significantly lower(P<0.05).Compared before and after treat-ment,the neuroelectrophysiological examination of the rPMS group was significantly improved(P<0.05).After 2 weeks of treatment,the tibial nerve motor conduction velocity,H reflex latency and IP peak in the conventional group were significantly faster than those before treatment(P<0.05).After 2 weeks of treatment,compared with the conventional group,there were significant differences in tibial nerve motor conduction velocity,peroneal nerve motor conduction velocity,superficial peroneal nerve sensory conduction velocity,sural nerve sensory conduction velocity,H reflex latency and IP peak(P<0.05).Conclusion rPMS can significantly improve and restore pain and nerve injury in patients with LDH.rPMS can be used as an effective adjuvant therapy.

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Humans ; Atherosclerosis/genetics* ; Autophagy/genetics* ; Cell Cycle Proteins/metabolism* ; Endothelial Cells/metabolism* ; Endothelium/metabolism* ; MicroRNAs/metabolism* ; Repressor Proteins/metabolism* ; RNA Splicing Factors ; Serine-Arginine Splicing Factors/genetics* ; RNA, Long Noncoding/metabolism*

Sarcopenia is an age-related disease that mainly involves decreases in muscle mass, muscle strength and muscle function. At the same time, the body fat content increases with aging, especially the visceral fat content. Adipose tissue is an endocrine organ that secretes biologically active factors called adipokines, which act on local and distant tissues. Studies have revealed that some adipokines exert regulatory effects on muscle, such as higher serum leptin levels causing a decrease in muscle function and adiponectin inhibits the transcriptional activity of Forkhead box O3 (FoxO3) by activating peroxisome proliferators-activated receptor-γ coactivator -1α (PGC-1α) and sensitizing cells to insulin, thereby repressing atrophy-related genes (atrogin-1 and muscle RING finger 1 [MuRF1]) to prevent the loss of muscle mass. Here, we describe the effects on muscle of adipokines produced by adipose tissue, such as leptin, adiponectin, resistin, mucin and lipocalin-2, and discuss the importance of these adipokines for understanding the development of sarcopenia.
Humans ; Adipokines ; Leptin ; Adiponectin ; Sarcopenia ; Muscles

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*

Objective By analyzing the epidemic characteristics and related indicators of SARS (2003) and COVID-19(2020), to explore the reasons for the similarities and differences of the two epidemics, so as to provide reference for epidemic prevention and control. Methods The general situation, clinical classification, activity history, contact history, family members’ contact and incidence of the two infectious diseases in Guangzhou were collected and used to analyze the time characteristics, occupational characteristics, age characteristics and other key indicators of the two diseases, including the number of cases, composition ratio (%), mean, median, crude mortality, etc. Results A total of 1 072 cases of SARS (2003) were included in the study. 353 of which were severe cases with the incidence of 30.13%. 43 cases of death were reported with a mortality rate of 4.01%. The average age was 46 years old, and 26.31% of the cases were medical staff. The interval time between first report to continuous zero reports was 129 days. As to COVID-19 (2020), a total of 346 cases were included. 58 of which were severe cases with the incidence of 16.67%. One case of death was reported with a mortality rate of 0.29%. The average age was 38 years old, and no hospital infection among medical staff was reported. The interval time between first report to continuous zero reports was 35 days. Conclusions The prevention and control strategies for COVID-19 (2010) are more effective compared to that of SARS (2003), and the emergency response procedures are worth to be evaluated and summarized.

Objective:Objective To explore the clinical values of next-generation sequencing (NGS) in bacterial 16S rRNA region and fungal ITS region for diagnosing and treating urinary tract infection (UTI) in renal transplant recipients.Methods:A total of 90 mid-stream clean-catch urine samples were collected from renal transplant recipients who were diagnosed with UTI at Hospital from January 2017 to December 2019. Each sample was equally divided and tested via NGS method and traditional urine culture separately. The results of pathogen test and detection rate were analyzed and compared.Results:And 21/90 sample were considered to be contaminated due to the identification of three or more kinds of microorganisms by culture. And among the remaining 69 samples, 36 (52.17%) cases tested positive by 16S rRNA sequencing, 25 (36.23%) positive by urine bacterial culture; meanwhile, 34(49.28%) tested positive by ITS sequencing and 4(5.80%) positive by urine fungal culture.Conclusions:The detection rate of both bacteria and fungi in NGS microorganism testing is higher than that in traditional urine culture ( P< 0.05). For renal transplant recipients with UTI, NGS microorganism testing is an effective supplement for traditional urine culture. Improving the detection rate and accuracy of etiology may enable an optimization of individualized treatment.

Objective To explore the relationship between fluoride exposure levels and thyroid structure and function in school-age children, and to provide epidemiological evidence for the prevention and treatment of thyroid diseases and for the control of high fluoride hazards. Methods In 2019, 217 children aged 8-10 years were selected from 3 primary schools in the historical high fluoride area of Tianjin. Basic information was collected by questionnaire surveys. Urine and blood samples were collected for the determination of urine iodine, urine fluoride, and thyroid hormone as well as antibodies. The dental fluorosis was examined by Dean’s method and the thyroid structure was examined by ultrasound. Results There was no significant difference in gender, age and BMI of children with different urine fluoride levels (P>0.05). There was significant difference in the degree of dental fluorosis among children with different urine fluoride levels（χ²=16.263, P=0.012）, and the prevalence of dental fluorosis was higher in children with higher urine fluorine level. There was no significant difference in goiter, nodule, hypothyroidism, hypothyroidism and antibody double positive distribution among children with different urine fluoride levels (P>0.05), but the distribution of TGAb+ or TPOAb+ showed significant difference (χ²=8.697，P=0.034). Logistic analysis showed that there was no correlation between urinary fluoride level and antibody single positive (P>0.05). Conclusion Compared with children with low fluoride exposure levels, children with high fluoride exposure have higher antibody single positive rate, but comprehensive analysis do not find a positive correlation between urinary fluoride level and thyroid structure and disease.

Objective:To compare epidemic characteristics between severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19).Methods:The general information, including epidemiological and clinical data of the confirmed cases during the epidemic period of the two infectious diseases was collected. The data of SARS in Guangzhou was derived from the technical files of Guangzhou Center for Disease Control and Prevention (GZCDC), including the statistical report and brief report of the epidemic situation (from January 2 to May 11, 2003);The data of COVID-19 in Wuhan was derived from the epidemic data published by Wuhan health and Health Committee's official website and other publicly reported documents (from December 9, 2019 to March 11, 2020). Descriptive analysis was used for a comparativeanalysis of the time and age characteristics, the number of cases, basic reproduction number (R0), proportion of medical staff in confirmed cases (%), crude mortality, etc.Results:A total of 1 072 cases of SARS in Guangzhou were included in the study. The incidence ratio of male to female was 1∶1.26. 43 cases of death were reported with a mortality rate of 4.01%. The median age was 36 years old. The proportion of medical staff in the early stage of the epidemic was 29.04% (88 cases). As to COVID-19 in Wuhan, a total of 49 978 cases were included, The incidence ratio of male to female was 1.04∶1. The 2 423 cases of death were reported with a mortality rate of 4.85%. The median age was 56 years old. The proportion of medical staff in the early stage of the epidemic was 30.43% (42 cases).Conclusion:The COVID-19 in Wuhan has the characteristics of high incidence and wide population. However, the epidemic situation is falling rapidly, and the prevention and control strategy needs to be adjusted timely. The prevention and control of nosocomial infection should be addressed in future.

Objective:To compare epidemic characteristics between severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19).Methods:The general information, including epidemiological and clinical data of the confirmed cases during the epidemic period of the two infectious diseases was collected. The data of SARS in Guangzhou was derived from the technical files of Guangzhou Center for Disease Control and Prevention (GZCDC), including the statistical report and brief report of the epidemic situation (from January 2 to May 11, 2003);The data of COVID-19 in Wuhan was derived from the epidemic data published by Wuhan health and Health Committee's official website and other publicly reported documents (from December 9, 2019 to March 11, 2020). Descriptive analysis was used for a comparativeanalysis of the time and age characteristics, the number of cases, basic reproduction number (R0), proportion of medical staff in confirmed cases (%), crude mortality, etc.Results:A total of 1 072 cases of SARS in Guangzhou were included in the study. The incidence ratio of male to female was 1∶1.26. 43 cases of death were reported with a mortality rate of 4.01%. The median age was 36 years old. The proportion of medical staff in the early stage of the epidemic was 29.04% (88 cases). As to COVID-19 in Wuhan, a total of 49 978 cases were included, The incidence ratio of male to female was 1.04∶1. The 2 423 cases of death were reported with a mortality rate of 4.85%. The median age was 56 years old. The proportion of medical staff in the early stage of the epidemic was 30.43% (42 cases).Conclusion:The COVID-19 in Wuhan has the characteristics of high incidence and wide population. However, the epidemic situation is falling rapidly, and the prevention and control strategy needs to be adjusted timely. The prevention and control of nosocomial infection should be addressed in future.