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.

BACKGROUND:Osteonecrosis is a common refractory disease in clinical practice,and observational studies have suggested that micronutrients may have a prognostic role in osteonecrosis.However,the specific causal association between micronutrients and osteonecrosis is not known. OBJECTIVE:To explore the causal association between micronutrients and osteonecrosis by Mendelian randomization using summary data from a large population-based genome-wide association study(GWAS)for clinical diagnosis and treatment. METHODS:The required exposure and outcome data(calcium,magnesium,iron,vitamin E,carotenoids,retinol&osteonecrosis)were extracted from the IEU OpenGWAS database,GWAS catalog database,and FinnGen database.Data were analyzed by bidirectional Mendelian randomization with inverse-variance weighted as the primary study method,and weighted median method,simple mode method,weighted mode method,and MR-Egger regression to complement the results.The reliability of the data was then verified through sensitivity analyses. RESULTS AND CONCLUSION:(1)The results found a positive correlation between serum iron concentration and osteonecrosis,while no correlation was found for other micronutrients.There was no reverse causality in all the data.(2)The results of sensitivity analysis showed a robust causality.(3)By Mendelian randomization method,this study provided evidence of causality between serum iron concentration and osteonecrosis,and understanding the causality of micronutrient elements on osteonecrosis can help in the clinical diagnosis and treatment of osteonecrosis,which is of great clinical significance.

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.

AIM: To explore the possible mechanism of Radix Tetrastigma (RT) on anti-rheumatoid arthritis (RA). METHODS: The rat model of RA was established by intradermal injection of complete Freund]s adjuvant into the right hind foot of SD rats. RT Extract with different dosage was continuous intragastric administration for 3 weeks, then, the degree of foot swelling, arthritis index score, joint heat and grip of each rat was measured respectively. ELISA was used to detect the expression levels of Interleukin (IL) 6, IL-17, IL-10, tumor necrosis factor-α, and rheumatoid factor. Fully automatic hemorheometer was applied to measure hemorheology indexes. The number of CD4

ObjectiveTo study the intervention of Huanglian Jiedutang on atherosclerosis （AS） in apolipoprotein E knockout （ApoE^-/-） mice induced by the high-fat diet. MethodThe ApoE^-/- mouse model of AS was induced by the high-fat diet， and Huanglian Jiedutang was used to intervene in the AS in the ApoE^-/- mice. The pathological changes of aorta were observed by hematoxylin-eosin （HE） staining. The levels of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected by an automatic biochemical analyzer. The protein expression levels of sirtuin-1 （SIRT1） and nuclear factor-kappa B （NF-κB） were determined by Western blot assay， and the mRNA expression levels of adenosine 5'-monophosphate-activated protein kinase （AMPK）， peroxisome proliferators-activated receptors α （PPARα）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and NOD-like receptor pyrin domain-containing 3 （NLRP3） were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultAs compared with the normal group， there was a large amount of lipid accumulation in the blood vessels of the model group. In the model group， the levels of serum TG， TC， and LDL-C were increased （P<0.01）， and the level of HDL-C was decreased （P<0.01）. The protein expression level of SIRT1 in the aorta was decreased， while that of NF-κB was increased in the model group （P<0.01）. The mRNA expression levels of IL-6， TNF-α， and IL-1β were higher （P<0.01）， while those of AMPK in the liver were lower in the model group （P<0.01）. Compared with the model group， the Huanglian Jiedutang group reduced the lipid accumulation and inflammatory reaction in the aorta of mice with AS， reduced the levels of TC， TG， and LDL-C （P<0.01）， and increased the level of HDL-C （P<0.01）. Huanglian Jiedutang significantly increased the protein expression level of SIRT1 in the aorta of ApoE^-/- mice （P<0.01） and decreased the protein expression levels of NF-κB in the aorta （P<0.05， P<0.01）. Huanglian Jiedutang down-regulated the mRNA expression levels of TNF-α， IL-6， IL-1β， and NLRP3 in the aorta （P<0.05， P<0.01）， and up-regulated the mRNA expression levels of AMPK and PPARα in the liver of ApoE^-/- mice （P<0.05， P<0.01）. ConclusionHuanglian Jiedutang has a certain intervention effect on the formation of atherosclerotic aortic plaque in ApoE^-/- mice. Its mechanism may be related to the decrease of serum TC， TG， and LDL-C levels， the increase of HDL-C levels， thus playing a role in lowering blood lipid， the increase of SIRT1 protein， the decrease of NF-κB protein， the decrease of inflammatory factors such as TNF-α and IL-6， which protects blood vessels from inflammatory injury， and the improvement of AMPK and PPARα levels to participate in autophagy and apoptosis.

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 To study the relation between alcohol-induced osteonecrosis of femoral head (AIONFH) related with high morbidity TCM constitution type with CYP2C8 gene polymorphisms.Methods Totally 152 Han nationality NONFH cases from Feburary 2014 to September 2015 from outpatient and the inpatient departments in Gansu Province Hospital of TCM were collected. 50 AIONFH cases were set as medical case group; meanwhile, 45 healthy volunteers were enrolled as control group. Database for medical materials of all patients and volunteers was established. TCM distribution for AIONFH patients was determined. Solution DNA extraction kit was used to extract DNA, and detect the concentration and purity of DNA. The target gene was amplified by PCR and the target gene was amplified by gel electrophoresis. The length of the fragment was confirmed to conduct target gene sequencing. With the results of sequencing and gel electrophoresis, the relation of AIONFH with CYP2C8 gene polymorphism in AIONFH patients with phlegm-dampness syndrome and the control group.ResultsThe CYP2C8 gene loci rs17110453 gene polymorphism was not statistically significant between the two groups (χ2=0.253,P>0.05). There was no significant difference in allele between the two groups (χ2=0.077,P>0.05). The risk of disease in CC genotype was 1.37 times higher than the AA genotype (95%CI: 0.339-5.540), without statistical significance (P>0.05). There was no significant difference in genotype and allele distribution between AIONFH patients with phlegm-dampness and non-phlegm-dampness and the control group (P>0.05).Conclusion CYP2C8 gene loci rs17110453 gene polymorphism A/C mutation has no obvious relation with AIONFH risk. There is no clear relationship between CYP2C8 gene loci rs17110453 gene polymorphism with AIONFH.

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 study the correlation between nontraumatic osteonecrosis of femoral head (NONFH) and ApoA1 polymorphism of blood stasis type.Methods Totally 93 cases of NONFH were selected as the case group, and 83 healthy volunteers were randomly selected as the control group. With TCM constitution questionnaire survey, the case group was screened out 32 cases of blood stasis NONFH type and 61 cases of non blood stasis NONFH type. In the case group and control group, the subjects took blood samples 2 mL, extracted DNA for PCR amplification, PCR products for DNA sequencing. G994T PAF-AH and rs9658282 gene NOS1 site polymorphism were detected for tatistical analysis.Results -75G/A gene AA ApoA1 genotype (OR: 2.578; 95%CI: 1.174-5.663;P=0.018) and A allele (OR: 1.726; 95%CI: 1.121-2.658;P=0.013) may be one of the risk factors of NONFH.Conclusion -75G/A gene ApoA1 may be related to the pathogenesis of NONFH. There was no correlation between the ApoA1 gene polymorphism of -75G/A gene and the pathogenesis of blood stasis NONFH. There was no correlation between the ApoA1 gene polymorphism of +83C/T gene and the pathogenesis of blood stasis NONFH.

Objective:To establish an optimal extraction technology for gastrodine in Tianma Gouteng decoctions. Methods: An orthogonal design with extract yield and gastrodine concentration as the indices was carried out to observe the influence of the extraction time, water amount and extract times on the extraction result. Results:The extract times showed significant influence on the extraction percentage of gastrodine. The best extraction parameters were as follows:adding 12-fold water and decocting 3 times with 1. 5h for each time. Conclusion:The established extraction process is feasible, which can be used in the preparation of the effective part for Tianma Gouteng decoctions with gastrodine concentration as the index.