Hepatitis E virus(HEV)is one of the most common pathogens in acute viral hepatitis.There are at least eight distinct genotypes of HEV.Only humans can contract HEV genotypes 1 and 2,but zoonotic viruses like genotypes 3 and 4 are mostly spread by eating undercooked or in-fected pork in some affluent nations.As a result,boars,both domestic and wild,are typically regar-ded as primary hosts of HEV.Nevertheless,during the past few years,a growing body of research has demonstrated that a number of other wild ruminant animals,such as wild deer and goats,are also susceptible to HEV infection.Determining their participation in the epidemiological cycle of hepatitis E thus requires an understanding of the risk variables that influence the transmission be-tween wild ruminants and humans.With an emphasis on published serological and molecular re-search,this review offers a broad summary of the body of knowledge currently available on the epi-demiology of HEV in wild ruminants.It addresses potential risk factors that could impact the spread of HEV among animals as well as their potential to serve as a source of infectious zoonotic illnesses.It presents an overview of the most recent developments in the epidemiology of HEV in wild ruminants and offers a framework for HEV prevention and management based on science.

AIM: To establish a method to investigate pharmacokinetics and bioequivalence of buthlphthalide injection. METHODS: An open, randomized, and two-cycle crossover study was conducted in 24 healthy volunteers. Plasma concentrations of buthlphthalide were determined by LC-MS/MS after administering a single dose of reference drug or test drug. Main pharmacokinetic parameters were calculated by Phoenix WinNonlin 6.4 software. RESULTS: For the test drug and the reference drug, the main pharmacokinetic parameters of flurbiprofen were as follows: AUC

Background::Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods::This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results::Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q 1-Q 3: 24.0-34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only. Conclusions::Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

Objective To investigate the research hotspots and trends in the field of immunotherapy for liver cancer in 2011-2020 based on bibliometric methods. Methods The Web of Science-SCI Expanded database was searched with the following search strategy: #1 TS = (Liver Neoplasms OR Neoplasms, Hepatic OR Neoplasms, Liver OR Liver Neoplasm OR Neoplasm, Liver OR Hepatic Neoplasms OR Hepatic Neoplasm OR Neoplasm, Hepatic OR Cancer of Liver OR Hepatocellular Cancer OR Cancers, Hepatocellular OR Hepatocellular Cancers OR Hepatic Cancer OR Cancer, Hepatic OR Cancers, Hepatic OR Hepatic Cancers OR Liver Cancer OR Cancer, Liver OR Cancers, Liver OR Liver Cancers OR Cancer of the Liver OR Cancer, Hepatocellular) AND #2 TS = (Immunotherapy OR Immunotherapies OR Immunity therapy); time span: 2011-2020; type of literature: Article; language: English. CiteSpace software was used to perform a visualized analysis of the articles in the field of immunotherapy for liver cancer published in 2011-2020 from the aspects of the distributions of year, country, institution, author, journal, and fund, times cited, and keywords, and the frequency, centrality, and clustering of keywords were discussed. Results A total of 1972 articles on immunotherapy for liver cancer were included, and the analysis showed that China was the country with the largest number of articles, Sun Yat-sen University was the institution with the largest number of articles, and Journal for Immunotherapy of Cancer was the journal with the largest number of articles. The research hotspots in this field included tumor-associated macrophages, oncolytic virus (such as adenovirus), tumor vaccine therapy, adoptive cellular immunotherapy, immune checkpoint inhibitors, and combined immunotherapy. The trend of this field was tumor vaccine therapy → immunotherapy for oncolytic virus → adoptive cellular immunotherapy → immune checkpoint inhibitor therapy. Conclusion Immunotherapy for liver cancer has undergone continuous development in the recent ten years, and with the research and development of tumor vaccine therapy, oncolytic virus, and immune checkpoint inhibitors and the improvement of immune checkpoint inhibitors, combined treatment based on immunotherapy is expected to further improve the clinical outcome of liver cancer.

Objective To explore the research hotspots and trends in the field of CSCs through the bibliometric analysis of the literature on CSCs. Methods Based on the core database of Web of Science, CiteSpace was used to analyze the annual distribution of published articles, authors, institutions, countries, journals, citations and keywords, and to explore the frequency, centrality and clustering of key words. Results (1) A total of 8131 articles were included after screening. China was the country with the largest number of articles, and Sun Yat-Sen University was the organization with the largest number of articles; (2) The hot spots in the field of CSCs are the research of CSCs in breast cancer and pancreatic cancer, the research of CSCs sorting and identification of molecular markers ALDH and genes PTEN, Sox2, C-myc, EZH2, the mechanism of EMT inducing the production of CSCs and promoting tumor metastasis, cellular and molecular mechanisms of CSCs resistance to chemical, radiation and targeted drug attacks, Wnt/β-catenin signaling pathway and tumor microenvironment regulate the differentiation of CSCs and targeted inhibition of CSCs in the treatment of malignant tumors; (3) The research trend of CSCs is CSCs stem research-biological mechanism of CSCs-CSCs application in the treatment of cancer. Conclusion The focus and direction of CSCs research are EMT inducing CSCs to promote tumor metastasis, CSCs resisting chemical attack, mesenchymal stem cells regulating CSCs, the metabolism of CSCs, and inhibitors targeting CSCs at present and in the future.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continually lead to worldwide human infections and deaths. Currently, there is no specific viral protein-targeted therapeutics. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear. Herein, we have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the -sheet core. Complemented by binding studies, our data provide several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, guiding the design of novel antiviral agents specific targeting to SARS-CoV-2.

Objective: To investigate the relationship between after-school schedule and bone mineral density in middle-school students in Shanghai, to provide a reference for taking targeted measures. Methods: From November 2017 to April 2018，eighteen classes of six middle schools in Shanghai (from urban districts, urban-suburb combined districts and suburban districts, respectively) were selected based on cluster random sampling. In each school, 2-4 classes were further randomly chosen in the 6th grade. Questionnaires were completed by 518 students and their parents, as well as physical examination and bone mineral density assessment. Results: The average time spent on after-school academic learning during weekends was 4.0 (IQR: 2.0, 6.0) h. The Z-score of bone density was 0.3 (IQR: -0.7, 1.0). The smooth curve fit model showed a non-linear relationship between after-school academic learning time during weekends and the Z-scores of bone mineral densities. A two-stage multiple linear regression analysis was further applied according to the fit results, and the results showed that when total afterschool academic learning time <4.5 hours during weekends, the learning time was inversely correlated with the bone density Z-scores (β=-0.11,P=0.01), and when the learning time ≥4.5 hours, there was no significant correlation between the learning time and bone density Z-scores (β=0.02, P=0.65). Parent and student questionnaires showed that there was a non-linear relationship between students’ daily time spent on outdoor sports-related activities and bone density Z-scores. When time spent on the outdoor activities ≥45 minutes per day, outdoor activities were positively correlated with bone density Z-scores (P<0.05). However, when the time spent on outdoor activities <45 minutes per day, there was no significant relationship between outdoor activities and bone density Z-scores (P>0.05). Conclusion Too much time on after-school academic learning during weekends or limited time on outdoor activities are both related to impaired bone mineral densities. Therefore, a reasonable after-school schedule for middle-school students is important for physical development, especially during weekends.

Objective To study the expression and the mechanism of miR-155in the villi of patients with unexplained recurrent spontaneous abortion (URSA).Methods The expression of miR-155 in the villi of 36 cases with URSA (URSA group) and 25 women with normal early pregnancy (control group) were detected by stem-loop real-time reverse transcription (RT) qPCR.Expression of hypoxia inducible factor-1 (HIF-1α),vascular endothelial cell growth factor(VEGF) and micro lymphatic vessel density (MVD) in the villi of were measured by immnohistochemical staining among two groups.Results (1) miR-155 expression:the mean miR-155 expression were 1.456 (0.489,2.459) in URSA group and 2.833 (1.740,3.794) in control group,which reached statistical difference (P ＜0.05).The mean expression of miR-155 of 1.683 (0.902,2.459) in URSA group with abortion times (≤ 3) was significantly higher than 1.229 (0.489,1.719) in URSA group with more than 4 times abortion (P ＜ 0.05).(2) Indexes:the expression of HIF-1α,VEGF and MVD value were 121 ± 12,134 ± 12,36 ± 6 in URSA group and 99 ± 10,109 ± 10,28 ±4 in control group,which reached statistical difference(P ＜ 0.01).The expression of HIF-1α,VEGF and MVD value of 119 ± 12,134 ± 12,35 ± 5 in URSA group with less than 3 times abortion was significantly lower than 128 ± 12,138 ± 12,43 ± 6 in URSA group with more than 4 times abortion (P ＜ 0.01).Conclusions The expression of miR-155 and HIF-1α is topically stimulated by oxygen signal.HIF-1α adjusts the transcription and translation of VEGF,which together involved in placental trophoblast invasion and placental angiogenesis.The low expression of miR-155 could interfere with expression of HIF-1α and VEGF,which might be involved in villous vascular dysplasia in URSA.

Objective To observe the effect of the outpatient mobile infusion system in the department of infectious outpatient night infusion.Methods From July to December in 2012,520 patients in department of infectious outpatient infusion in our hospital were selected and were divided into the observation group (using outpatient mobile infusion system)and the control group (adopting conventional infusion) with 260 cases in each group.The infusion effect was compared between two groups.Results The average occupancy per patient care time in the observation group was less than the control group,the difference was statistically significant.The satisfaction degree in the observation group was higher than that of the control group,the difference was statistically significant.There was no nursing error occurred in both of the observation group or the control group.Conclusion The use of outpatient mobile infusion system can significantly improve the nurses work efficiency,ensure nursing safety,improve quality of care and patients' satisfaction degree.

Objective To investigate the distribution of eosinphililic neurons ( ENs),reactive astrocytes ( RAs),and infarction after transient cerebal ischemia,and the time profile of pathomorphological changes.Methods Unilateral forebrain ischemia was induced in Mongolian gerbils by two 10 minutes unilateral common carotid artery occlusions with a 5 hours interval.Laser Doppler flowmetry was used to detect intra-ischemic anterior cortex blood flow.Animals were sacrificed at 24 hours,4 days,2 weeks,4 weeks,16 weeks and the brain were prepared for pathomorphological assay.Results Intra-ischemic laser Doppler flowmetry show significant ischemia during carotid artery occlusion:22.1％ ± 9.5％,26.3％ ± 4.9％,37.5％ ± 3.5％,F =67.219,P ＜ 0.01 ; the decrease was significantly greater in the anterior cortex.ENs appeared in middle and deep layers at 24 hours postischemia,and ENs area extend to all layers of cortex by 4 days.Large areas of high EN density ( ≥80/mm2) evolved to infarcts between 4 days and 4 weeks.Posterior cortex evolved to low EN area ( ＜ 80/mm2) without transformation into infarcts.RAs were consistently distributed in areas with ENs,and RA areas with high EN density were largely transformed into infarcts between 4 days and 4 weeks. Delayed astrocytic death took place in the RA areas with high EN density.Conclusion Density of ENs is an important indicator of delayed astrocytic death and infarction in postischemic tissue.