Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, damage to bone tissue microstructure, increased bone fragility, and susceptibility to fractures, while sarcopenia is a syndrome characterized by progressive reduction in overall muscle mass and functional decline. Based on the common pathophysiological mechanism and close correlation between the two, the concept of "osteosarcopenia" has gradually emerged to describe the simultaneous attenuation of muscles and bones. Signaling pathways serve as important signal transmission channels between muscles and bones, and if abnormal, they can lead to osteosarcopenia. The aim of this article, therefore, is to review the signaling pathways related to osteogenesis and myogenesis, such as Hedgehog, Hippo, mTOR, MAPK, in order to provide new ideas for targeted treatment of osteosarcopenia.

Objective To analyze the epidemiological characteristics and influence factors of human brucellosis in Jilin Province and provide scientific basis for enacting prevention and control strategy to brucellosis in the new period.Methods Descriptive epidemiological methods were used to analyze the epidemiological characteristics (regional distribution,time distribution,population distribution,etc.),influencing factors (risk factors,protective measures and epidemic prevention),epidemic links,detection methods,clinical stages and prognosis of reported brucellosis cases in Jilin Province from 2011 to 2017.Results From 2011 to 2017,12 116 cases of brucellosis were reported in Jilin Province,with an average incidence of 6.30/100 000.The annual incidence rates were 7.51/100 000,7.11/100 000,7.36/100 000,6.58/100 000,5.90/100 000,5.38/100 000 and 4.24/100 000,respectively.The reported cases were mainly distributed in Songyuan City and Baicheng City,accounting for 73.29％ (8 880/12 116) of the total number of reported cases;the time was from January to July,and the peak was from March to May.The age of onset ranged from 20 to 70 years old,mainly in young and middle-aged adults,accounting for 95.86％ (11 615/12 116) of the total number of reported cases.The following factors were studied:to take protective measures rate,human and animal mixed live,the same water source,colony house housing disinfection,manage abortion,buy animal quarantine,raise livestock immunity,and the proportion of these factors in each year was 24.38％ to 43.33％,3.11％ to 17.35％,63.68％ to 76.58％,25.40％ to 35.07％,21.66％ to 34.49％,9.32％ to 29.66％,26.09％ to 45.45％,respectively.The main infection source was sick sheep,accounting for 96.72％ (11 718/12 116).Skin mucosa was the main route of transmission,followed by digestive tract,accounting for 61.55％ (7 458/12 116) and 34.17％ (4 140/12 116),respectively.The main transmission factors were apoblema and flying dust,accounting for 55.68％ (6 746/12 116) and 35.62％ (4 316/12 116),respectively.The number of reported cases of brucellosis was 90.55％ (10 971/12 116) through passive monitoring.The clinical stage was mostly acute,accounting for 92.01％ (11 148/12 116).Healing and improvement accounted for 60.80％ (7 367/12 116) and 37.93％ (4 596/12 116),respectively.Conclusions Brucellosis has dropped slightly in Jilin Province in 2011-2017,but remains high;the epidemic situation is still grim.We should further strengthen monitoring,health education and health promotion,team construction,in order to effectively control the occurrence of human brucellosis.

OBJECTIVE: CDKN2B-AS1 polymorphisms were shown to associate with the risk of stroke in European. The goal of this study was to evaluate the contribution of CDKN2B-AS1 rs1333049 to the risk of hemorrhagic stroke (HS) and brain tumor (BT) in Han Chinese. METHODS: A total of 142 HSs, 115 BTs, and 494 controls were included in the current association study. The genotyping test was performed using the melting temperature shift method. RESULTS: We failed to validate the association of CDKN2B-AS1 rs1333049 with the risk of brain disease. Significantly higher levels of low-density lipoprotein cholesterol (LDL-C) (p=0.027), high-density lipoprotein cholesterol (HDL-C) (p<0.001) and total cholesterol (TC) (p<0.001) were found in HSs in the genotype GG/GC carriers, but not the genotype CC carriers (p>0.05). The meta-analysis of 10 studies among 133,993 individuals concluded that rs1333049 of CDKN2B-AS1 gene was likely to increase a 16% incidence rate of cerebrovascular disease (CD) among various populations (odds ratio 1.16, 95% confidence interval 1.08–1.25; p<0.0001, random-effect method). CONCLUSION: Our case-control study identified rs1333049 genotypes showed different association with the concentration of the LDL-C, HDL-C and TC in the HS patients. Meta-analysis supported the association between rs1333049 and CD risk in various populations, although we were unable to observe association between rs1333049 and the risk of HSs in Han Chinese.
Asian Continental Ancestry Group ; Brain Diseases* ; Brain Neoplasms ; Brain* ; Case-Control Studies* ; Cerebrovascular Disorders ; Cholesterol ; Freezing ; Genotype ; Humans ; Incidence ; Lipoproteins ; Methods ; Stroke

Objective To investigate the level of CD31 molecule expression on peripheral T lymphocytes of patients with chronic hepatitis B (CHB),and to study the relationship between the expression of CD31 molecule and serum ALT levels,serum levels of HBV DNA and HBeAg.Preliminarily explore the relationship between the expression frequency of CD31 molecule and patients CHB,in order to understand changes in different immune status when chronic HBV infecting.Methods A total of non-antiretroviral therapy 42 patients with CHB and 25 healthy volunteers were enrolled for the study.In peripheral blood,separated lymphocytes conventionally,the percentage of CD4 + 、CD8 + 、CD31 + 、CD31 + CD4 + 、CD31 + CD8 + 、CD31 + CD4 +/CD4 + 、CD31 + CD8 +/CD8 + cells were assessed by flow cytometry,serum ALT levels were tested by automatic biochemical analyzer,serum HBVDNA levels were determined by real-time fluorescent quantitative PCR,and the serological markers of HBV were examined through chemiluminescence simultaneously.Results The percentages of CD4 + 、CD31 + 、CD31 + CD4 + 、CD31 +CD4 +/CD4 + cells in patients with CHB were significantly less than the healthy(P ＜ 0.05);the percentages of CD31 + 、CD31 + CD4+ 、CD31 + CD8+ 、CD31 + CD4+/CD4+ cells in ALT ＜2ULN group of patients with CHB were significantly lower than ALT≥2ULN group(P ＜ 0.05);serum HBVDNA loads lower group (＞103-105copies/ml),middle group (＞ 105-107 copies/ml) and higher group of HBVDNA (＞ 107-109 copies/ml) CD31 molecule expression frequency were on the rise,but no statistically significant difference were observed in the comparison between groups (P ＞ 0.05);the percentages of CD31 + 、CD31 + CD8 + 、CD31 + CD4 +/CD4 + cells in the HBeAg-negative group were significantly lower than HBeAg-positive group (P ＜0.05).Conclusions The frequency of CD31 molecule expression on peripheral T lymphocytes of patients with CHB were declined;there is a certain relationship between the frequency of CD31 molecule expression and serum ALT levels,different loads of HBVDNA,HBeAg positive or negative in patients with CHB;chronic HBV infection of immune status may be associated with T cell surface expression of CD31 molecule frequency.

AIM:To investigate the clinicopathological significance of the protein expression of phosphorylated ezrin at threonine 567 ( pEZRThr567 ) in lung squamous cell carcinoma, adjacent tissues and normal tissues.METHODS:pEZRThr567 protein was detected in lung squamous carcinoma, adjacent and normal tissues by the method of immunohisto-chemistry.The correlation of pEZRThr567 expression with clinicopathological parameters of lung squamous carcinomas was al-so analyzed.The localization of pEZRThr567 was detected by immunofluorescence staining in lung squamous cell line EBC-1. RESULTS:The protein expression of pEZRThr567 in lung squamous carcinoma was significantly higher than that in the adja-cent and normal lung tissues (P<0.01).pEZRThr567 mainly localized on the cell membrane, and its over-expression signi-ficantly correlated with the differentiation, clinical stage and lymph node metastasis in lung squamous carcinoma.CON-CLUSION:pEZRThr567 may be an effective biomarker for prediction of malignant potential and poor prognosis of lung cancer.

Objective To prospectively compare MR pulmonary perfusion imaging with quantitative HRCT for the detection of mild chronic obstructive pulmonary disease (COPD) and classification of COPD.Methods Sixty-two consecutive patients with COPD and 17 healthy volunteers underwent pulmonary function test (PFT),HRCT and MR perfusion imaging on the same day.According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD),all COPD patients were classified into 4 stages:stage Ⅰ (n =19),stage Ⅱ (n =17),stage Ⅲ (n =14),stage Ⅳ (n =12).The signal intensity of perfusion defects (SIPD),signal intensity of normal lung perfusion (SInormal) on 3D MR perfusion were obtained through postprocessing and the signal intensity ratio (RSI) was calculated.The total lung volume (TLV) was calculated automatically on HRCT and the total emphysema volume (TEV) was obtained by applying -950 HU thresholds.The TEV/TLV was deduced as emphysema index (EI).Several comparisons were made between the volunteers and COPD patients by one-way ANOVA and Kruskal-Wallis test.Results The RSI,SIPD,PEI,MSI,MSD values of MRI perfusion in volunteers (43.9 ± 7.2,48.2 ± 19.7,31.4,55.7,44.1) were significantly different from those in patients with COPD (18.1 ± 8.1,47.4 ± 20.0,8.6,30.2,22.7) (P ＜ 0.01).The RSI showed a significant difference between stage Ⅰ (24.4 ± 9.8) and stage Ⅲ (15.9 ± 5.3) or Ⅳ (9.2 ± 2.7) and between stage Ⅱ (19.9 ± 3.1) and stage Ⅳ (t =4.05-6.64,P ＜0.01).However,all MRI perfusion parameters between stage Ⅰ and stage Ⅱ,stage Ⅱ and stage Ⅲ,stage Ⅲ and stage Ⅳ were no differences (t =2.00-4.46,P ＞ 0.05).The median of EI in volunteers and stage Ⅰ-Ⅳ COPD patients were 1.2,3.8,8.0,13.7,18.3,and the quartile range were 3.7,7.1,9.2,10.5,7.7,respectively.The EI in volunteers showed significant differences with that of stage Ⅱ-Ⅳ COPD and the EI of stage Ⅳ was different from that of stage Ⅱ or Ⅰ (t =-7.32--1.85,P ＜ 0.01),but there was no significant difference between volunteers and stage Ⅰ COPD (t =-1.99,P ＞ 0.05).Conclusions The RSI of MRI is more sensitive than that of HRCT for assessing mild COPD.The severity of COPD could be reflected by MRI perfusion and HRCT.

The authors discussed about how to integrate the advantages of different medical research resources to construct Shanghai Academy of Medical Sciences,which will provide substantial support for medical innovation in Shanghai.Principles were proposed concerning the administrative system and management mechanism to enhance the performance.The Academy is expected to improve medical research and clinical performance,especially to help resolve some major diseases and incurable diseases.Ultimately,the Academy will develop into an advanced research center linking laboratory research and clinical medicine.

During the course of standardized residents training,the performance appraisal management of the residents was used besides other regular management methods.The allowances of residents were decided monthly by the evaluation and assessment of many kinds of tests or examinations.Through this new measure,the learning enthusiasm of residents could be fully motivated.The authoritative effectiveness of management was enhanced enormously.Meanwhile,the quality of the educational and training has also been improved greatly.This method could be very useful for the training process.

A descriptive study to investigate the situation of cross-cultural adaptation and health status among medical international students was carried out using cluster sampling method and self-designed questionnaire in Dalian Medical University.148 international students come from 24 countries.There are 5 religions belief among these students.Islam,Catholic,Hindu,Buddhism and Sikhism.The main obstacles of cross-cultural adaptation are language,accommodation and diet.Economic status and stress of interpersonal relationship are also the main causes affecting the physical and mental health of medical international students.