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 We aimed to investigate the effects of Biejiajian Pills on MHCC-97H hepatoma cells and whether Biejiajian Pills regulate the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway through miR-885-5p.Methods SPF SD rats (n = 10) were randomly divided into the blank group and the Biejiajian Pills (1.1 g/kg) group to prepare blank and Biejiajian Pills-containing serum. MHCC-97H cells in the logarithmic growth phase were divided into the model group, blank serum groups with different concentrations (5％, 10％, 15％, and 20％), the serum containing Biejiajian Pills group, and the blank group without cells. Cell proliferation was detected by the CCK-8 assay, and the optimal intervention time and concentration of drug-containing serum were screened. MHCC-97H cells were divided into the blank control group (no intervention), the Biejiajian Pills-containing serum group (20％ Biejiajian Pills-containing serum), the miR-885-5p mimics group (transfected with miR-885-5p mimics), the miR-NC group (transfected with miR-885-5p NC), and the Biejiajian Pills-containing serum + miR-885-5p mimics group (treated with 20％ Biejiajian Pills-containing serum and transfected with miR-885-5p mimics). Cells in each group were cultured for 72 hours. A dual luciferase reporter assay was conducted to verify the targeting relationship between miR-885-5p and EGFR. Cell proliferation was detected by the CCK-8 assay, cell migration and invasion abilities were detected by the cell scratch assay and the Transwell invasion assay. Annexin V-APC/PI double staining was performed to detect the apoptosis level, and real-time fluorescence quantitative PCR (RT-qPCR) analysis was conducted to determine the mRNA expression levels of miR-885-5p, EGFR, MEK, and ERK1/2. The expression levels of EGFR, p-EGFR, MEK, p-MEK, ERK1/2, p-ERK1/2, matrix metalloproteinase 1 (MMP1), and CyclinD1 were determined by Western blotting analysis. The subcutaneous tumor model of MHCC-97H hepatoma cells in nude mice was established by subcutaneous injection to observe the inhibitory effect of Biejiajian Pills of different doses(0.55,1.1,2.2 g/kg).Results The optimal concentration and intervention time of Biejiajian Pills-containing serum were 20％ and 72 hours, respectively. Meanwhile, the dual luciferase reporter assay showed that miR-885-5p could directly target EGFR. No statistical significances between the blank control group and the miR-NC group were observed (P>0.05). Compared with the blank control group, the proliferation rates of MHCC-97H hepatoma cells in the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group were significantly decreased (P<0.01), and their migration and invasion abilities were significantly decreased (P<0.05, P<0.01). At the same time, the protein expression levels of CyclinD1 and MMP1, which are closely related to cell proliferation and invasion, were significantly downregulated (P<0.05, P<0.01). The proportions of late apoptotic cells and the proportion of total apoptotic cells were significantly increased (P<0.01). In the Biejiajian Pills-containing serum group, the miR-885-5p mimics group, and the Biejiajian Pills-containing serum + miR-885-5p mimics group, miR-885-5p mRNA was significantly upregulated (P<0.01) and EGFR, MEK, and ERK1/2 were significantly downregulated at the mRNA level (P<0.05, P<0.01). EGFR, MEK, and ERK1/2 phosphorylation was inhibited (P<0.01), and the Biejiajian Pills-containing serum + miR-885-5p mimics group showed the best effect (P<0.05, P<0.01). The subcutaneous liver tumor model in nude mice verified that Biejiajian Pills can inhibit tumor growth in a dose-dependent manner. Conclusion Biejiajian Pills can promote apoptosis of MHCC-97H hepatoma cells and inhibit their proliferation, invasion, and migration. The mechanism may be related to the targeted regulation of the EGFR/MAPK/ERK signaling pathway by miR-885-5p.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies

Humans ; COVID-19/complications* ; Pericarditis/complications*

Animals ; Genomics ; Humans ; Serogroup ; Streptococcal Infections ; Streptococcus suis/isolation & purification* ; Swine ; Swine Diseases

Objective - To analyze the relationship between cobalt level of post shift urine and individual exposure level of ， cobalt and its compounds in cobalt exposed workers and to explore the feasibility of using urine cobalt as a biomarker. Methods - A total of 148 occupational cobalt exposed workers from a new material company were selected as the exposed ， - - group and 44 non occupational cobalt exposed workers from the company were selected as the control group using the typical sampling method. The exposure concentration of time weighted average of cobalt and its compounds in the workplace air of the - two groups was determined by inductively coupled plasma mass spectrometry as the individual exposure level. The cobalt levels - - of pre shift and post shift urinary samples of the two groups were detected by this method. The linear relationship between the - cobalt level of post shift urine and the individual exposure level of cobalt and its compounds in the air of the workplace was Results - 3 analyzed. The individual exposure level of cobalt and its compounds in the exposed group was 1.10 131.71 μg/m with （M） 3 the median of 12.23 μg/m. No cobalt and its compounds were detected in the workplace air in the control group. The cobalt - - levels of pre shift and post shift urines in exposed group were higher than those in the control group at the same time point （M： vs ， vs ， P ） - - 1.54 0.56 μg/L 8.77 0.83 μg/L all <0.01 . The cobalt level of post shift urine was higher than that in pre shift （M： vs ，P ）， urine in the exposed group 8.77 1.54 μg/L <0.01 and it was positively correlated with the individual exposure level （ ，P ） ， of cobalt and its compounds Spearman correlation coefficient=0.86 <0.01 . After common logarithm conversion the linear regression equation of the cobalt level of post shift urine and the common logarithm of individual exposure level of cobalt and （x） ：ŷ x（ ；F ， its compounds in the exposed group was as follows = −0.178 + 0.988 coefficient of determination=0.72 =374.75 P ；t ， P ） Conclusion - <0.01 = - 19.36 <0.01 . There was a linear correlation between cobalt level of post shift urine and occupational cobalt exposure level of cobalt exposed workers. Urinary cobalt can be used as a biomarker of occupational cobalt

Objective: To evaluate the recognition of acute respiratory infection (ARI) by a pretrained model based on electronic medical records (EMRs). Methods: 38 581 EMRs were obtained from Chongqing University Three Gorges Hospital in December 2021. Bidirectional encoder representation from transformers (BERT) pretrained model was used to identify ARI in EMRs. The results of medical professionals were considered as the gold standard to calculate the sensitivity, specificity, Kappa value, and area under the curve of the receiver operating characteristic (AUC). Results: There were 3 817 EMRs in the test set, with 1 200 ARIs. A total of 1 205 cases were determined as ARI by the model, with a sensitivity of 92.67% (1 112/1 200) and a specificity of 96.45% (2 524/2 617). The model identified ARI with similar accuracy in males and females (AUCs 0.95 and 0.94, respectively), and was more accurate in identifying ARI cases in those aged less than 18 than in adults 18-59 and adults 60 and older (AUCs 0.94, 0.89 and 0.94, respectively). The current model had a better identification of ARIs in outpatient patients than that in hospitalized patients, with AUCs of 0.74 and 0.95, respectively. Conclusion: The use of the BERT pretrained model based on EMRs has a good performance in the recognition of ARI cases, especially for the outpatients and juveniles. It shows a great potential to be applied to the monitoring of ARI cases in medical institutions.
Adult ; Male ; Female ; Humans ; Electronic Health Records ; Respiratory Tract Infections/diagnosis* ; Outpatients

Objective: To investigate the occurrence of live-born twins with birth weight-discordance and its relationship to adverse birth outcomes. Methods: A retrospective analysis was performed on 4 011 pairs of live-born twins in the Third Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2020. Based on the birth-weight discordance (∆BW, ∆BW=(birth-weight_big-birth-weight_small)/birth-weight_big×100%)), twins were divided into 4 groups, including ∆BW≤15%,>15%-20%,>20%-25%, and>25%. The differences in maternal and neonatal outcomes among 4 groups were explored. Then the correlation between ∆BW and neonatal adverse outcomes were explored. Results: The ΔBW was 9 (4, 16)% and males were accounted for 53.8% (4 315 cases) of 4 011 pairs of twins. The gestational age was (35.3±2.7) weeks at birth. There were 2 908 pairs (72.5%) of twins with ΔBW≤15%, 481 pairs (12.0%) with ΔBW>15%-20%, 281 pairs (7.0%) with ΔBW 20%-≤25%, and 341 twin pairs (8.5%) with ΔBW>25%. With ∆BW of 20% as the diagnostic cutoff, the incidence of birth weight discordance was 15.5% (622/4 011). The proportion of natural births in the ∆BW≤15% group was higher than that in the ∆BW>15%-20% group (10.5% (288/2 740) vs. 6.3% (29/463), P<0.008 3). The ∆BW>25% group had a significantly higher prevalence of maternal hypertensive disorders during pregnancy than that of the other 3 groups (25.5% (87/341) vs. 16.7% (47/281) vs.17.3% (83/480) vs. 13.8% (400/2 899), all P<0.008 3). Univariate analysis found that the ΔBW>25% group had a lower gestational age and a higher rate of preterm birth than the other groups. The rate of extremely low birth weight (ELBW) or very low birth weight (VLBW), small for gestational age (SGA), and transferring to the department of neonatology in the smaller twins were significantly different among the 4 groups (all P<0.05). Multivariate analysis showed that higher degree of birth weight discordance was all positively associated with the rate of ELBW, SGA, and transferring to the department of neonatology in smaller twin, even after adjusting maternal age and gestational hypertension, year of birth, mode of delivery, gender, and gestational age (all P<0.05). Moreover, the Mantel-Haenszel test also indicated that there were significantly low to moderate correlations between ΔBW and the unfavorable outcomes (r=0.22, 0.53, 0.21, all P<0.001, respectively). The receiver operating characteristic (ROC) curve found that adverse birth outcomes would be well predicted by birth weight-discordant when the diagnostic cut-off of ΔBW was 12%-17%, with an acceptable sensitivity (0.53-0.78) and a high specificity (0.72-0.79). Conclusions: Birth weight discordant is not uncommon in live-born twins, and is associated with adverse outcomes including ELBW, SGA, and transferring to the department of neonatology in the small twins. Besides, the risk is linearly related to the increase of ΔBW. In the future, more researches are needed to explore the underline mechanism and long-term impact of birth weight discordance, to guide the prevention and management.
Birth Weight ; Female ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Newborn, Diseases ; Male ; Pregnancy ; Premature Birth/epidemiology* ; Retrospective Studies ; Twins