Dysregulated microRNAs as a biomarker for diagnosis and prognosis of hepatitis B virus-associated hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy with a high incidence and fatality rate worldwide.Hepatitis B virus(HBV)infection is one of the most important risk factors for its occurrence and development.Early detection of HBV-associated HCC(HBV-HCC)can improve clinical decision-making and patient outcomes.Biomarkers are extremely helpful,not only for early diagnosis,but also for the development of therapeutics.MicroRNAs(miRNAs),a subset of non-coding RNAs approximately 22 nucleotides in length,have increasingly attracted scientists’attention due to their potential utility as biomarkers for cancer detection and therapy.HBV profoundly impacts the expression of miRNAs potentially involved in the development of hepatocarcinogenesis.In this review,we summarize the current progress on the role of miRNAs in the diagnosis and treatment of HBV-HCC.From a molecular standpoint,we discuss the mechanism by which HBV regulates miRNAs and investigate the exact effect of miRNAs on the promotion of HCC.In the near future,miRNA-based diagnostic,prognostic,and therapeutic applications will make their way into the clinical routine.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV) infected pneumonia(standard version)

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province;and then named "2019 novel coronavirus(2019-nCoV)" by the World Health Organization(WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development;we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control(including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Effect of endogenous insulin-like growth factor and stem cell factor on diabetic colonic dysmotility

AIM: To investigate whether the reduction of stem cell factor (SCF) is mediated by decreased endogenous insulin-like growth factor (IGF)-1 in diabetic rat colon smooth muscle. METHODS: Sixteen Sprague-Dawley rats were randomly divided into two groups: control group and streptozotocin-induced diabetic group. After 8 wk of streptozotocin administration, colonic motility function and contractility of circular muscle strips were measured. The expression of endogenous IGF-1 and SCF was tested in colonic tissues. Colonic smooth muscle cells were cultured from normal adult rats. IGF-1 siRNA transfection was used to investigate whether SCF expression was affected by endogenous IGF-1 expression in smooth muscle cells, and IGF-1 induced SCF expression effects were studied. The effect of high glucose on the expression of endogenous IGF-1 and SCF was also investigated. RESULTS: Diabetic rats showed prolonged colonic transit time (252 ± 16 min vs 168 ± 9 min, P < 0.01) and weakness of circular muscle contraction (0.81 ± 0.09 g vs 2.48 ± 0.23 g, P < 0.01) compared with the control group. Endogenous IGF-1 and SCF protein expression was significantly reduced in the diabetic colonic muscle tissues. IGF-1 and SCF mRNA expression also showed a paralleled reduction in diabetic rats. In the IGF-1 siRNA transfected smooth muscle cells, SCF mRNA and protein expression was significantly decreased. IGF-1 could induce SCF expression in a concentration and time-dependent manner, mainly through the extracellular-signal-regulated kinase 1/2 signal pathway. High glucose inhibited endogenous IGF-1 and SCF expression and the addition of IGF-1 to the medium reversed the SCF expression. CONCLUSION: Myopathy may resolve in colonic motility dysfunction in diabetic rats. Deficiency of endogenous IGF-1 in colonic smooth muscle cells leads to reduction of SCF expression.

Perceived infection transmission routes, infection control practices, psychosocial changes, and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey

Background:Many healthcare workers were infected by coronavirus disease 2019(COVID-19)early in the epidemic posing a big challenge for epidemic control.Hence,this study aims to explore perceived infection routes,influencing factors,psychosocial changes,and management procedures for COVID-19 infected healthcare workers.Methods:This is a cross-sectional,single hospital-based study.We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29,2020.All participants completed a validated questionnaire.Electronic consent was obtained from all participants.Perceived causes of infection,infection prevention,control knowledge and behaviour,psychological changes,symptoms and treatment were measured.Results:Finally,103 professional staff with COVID-19 finished the questionnaire and was included(response rate:98.1%).Of them,87 cases(84.5%)thought they were infected in working environment in hospital,one(1.0%)thought their infection was due to the laboratory environment,and 5(4.9%)thought they were infected in daily life or community environment.Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively.Forty-three(41.8%)thought their infection was related to protective equipment,utilization of common equipment(masks and gloves).The top three first symptoms displayed before diagnosis were fever(41.8%),lethargy(33.0%)and muscle aches(30.1%).After diagnosis,88.3%staff experienced psychological stress or emotional changes during their isolation period,only 11.7%had almost no emotional changes.Arbidol(Umifenovir;an anti-influza drug;69.2%)was the drug most commonly used to target infection in mild and moderate symptoms.Conclusion:The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases.Positive psychological intervention is necessary.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline(updated version)

The novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the cause of a rapidly spreading illness,coronavirus disease 2019(COVID-19),affecting more than seventeen million people around the world.Diagnosis and treatment guidelines for clinicians caring for patients are needed.In the early stage,we have issued"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infected pneumonia(standard version)";now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline.We formed a working group of clinical experts and methodologists.The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas:chemoprophylaxis,diagnosis,treatments,and discharge management.We searched the literature for direct evidence on the management of COVID-19,and assessed its certainty generated recommendations using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)approach.Recommendations were either strong or weak,or in the form of ungraded consensus-based statement.Finally,we issued 34 statements.Among them,6 were strong recommendations for,14 were weak recommendations for,3 were weak recommendations against and 11 were ungraded consensus-based statement.They covered topics of chemoprophylaxis(including agents and Traditional Chinese Medicine(TCM)agents),diagnosis(including clinical manifestations,reverse transcription-polymerase chain reaction(RT-PCR),respiratory tract specimens,IgM and IgG antibody tests,chest computed tomography,chest X-ray,and CT features of asymptomatic infections),treatments(including lopinavirritonavir,umifenovir,favipiravir,interferon,remdesivir,combination of antiviral drugs,hydroxychloroquine/chloroquine,interleukin-6 inhibitors,interleukin-1 inhibitors,glucocorticoid,qingfei paidu decoction,lianhua qingwen granules/capsules,convalescent plasma,lung transplantation,invasive or noninvasive ventilation,and extracorporeal membrane oxygenation(ECMO)),and discharge management(including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge).We also created two figures of these recommendations for the implementation purpose.We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Extracorporeal Membrane Oxygenation Therapy for Critically Ill Coronavirus Disease 2019 Patients in Wuhan,China:A Retrospective Multicenter Cohort Study

Currently,little in-depth evidence is known about the application of extracorporeal membrane oxygenation(ECMO)therapy in coronavirus disease 2019(COVID-19)patients.This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan,China.The patients were followed up until June 30,2020.Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning.Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation(IMV)-only therapy.Of 88 patients receiving ECMO therapy,27 and 61 patients were and were not successfully weaned from ECMO,respectively.Additionally,15,15,and 65 patients were further weaned from IMV,discharged from hospital,or died during hospitalization,respectively.In the multivariate logistic regression analysis,a lymphocyte count≤0.5×10^(9)/L and D-dimer concentration>4×the upper limit of normal level at ICU admission,a peak PaCO_(2)>60 mmHg at 24 h before ECMO initiation,and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning.In the propensity scorematched analysis,a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group.The presence of lymphocytopenia,higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis.Tracheotomy could facilitate weaning from ECMO.ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris

Objective: To discuss the effect of Yixinkangtai Capsule combined with diltiazem on endothelial function, blood viscosity and lipid metabolism in patients with unstable angina pectoris. Methods: A total of 150 patients with unstable angina pectoris who were treated in the hospital between February 2014 and February 2017 were divided into the control group (n=75) and the research group (n=75) according to the random number table method. Control group received clinical conventional therapy, research group received Yixinkangtai Capsule combined with diltiazem therapy on the basis of conventional therapy, and both groups received 3 months of treatment. Differences in endothelial function, blood viscosity and lipid metabolism were compared between the two groups of patients before and after treatment. Results: Before treatment, the differences in serum levels of endothelial function indexes, blood viscosity indexes and lipid metabolism indexes were not statistically significant between the two groups. After 3 months of treatment, serum NO level of research group was higher than that of control group while ET-1 level was lower than that of control group;serum blood viscosity index TXB2 content of research group was lower than that of control group while PGI2 content was higher than that of control group;serum lipid metabolism indexes TG, TC and LDL-C contents of research group were lower than those of control group while HDL-C content was higher than that of control group. Conclusion: Yixinkangtai Capsule combined with diltiazem therapy can effectively optimize the endothelial function, reduce the blood viscosity and balance the lipid metabolism in patients with unstable angina pectoris.

Effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure

Objective: To discuss the effect of adjuvant levosimendan therapy on neuroendocrine hormones and cytokines in elderly patients with chronic heart failure. Methods: A total of 100 elderly patients with chronic heart failure who were treated in the hospital between March 2014 and March 2017 were divided into control group and levosimendan group by random number table, each with 50 cases. Control group received clinical routine therapy for chronic heart failure, and levosimendan group received routine therapy combined with adjuvant levosimendan therapy. The differences in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes were compared between the two groups before and after treatment. Results: At T0, there was no statistically significant difference in serum levels of RAAS indexes, thyroid hormones, myocardial damage indexes and endothelial function indexes between the two groups. At T1, serum RAAS indexes PRA, AngⅡ and ALD levels of levosimendan group were lower than those of control group;serum thyroid hormones TT3, TT4, FT3 and FT4 levels of levosimendan group were higher than those of control group;serum myocardial damage indexes cTnⅠ, H-FABP and NT-proBNP levels of levosimendan group were lower than those of control group;serum endothelial function index NO level of levosimendan group was higher than that of control group while ET-1 level was lower than that of control group. Conclusion: Adjuvant levosimendan therapy for elderly patients with chronic heart failure can effectively adjust the secretion of neuroendocrine hormones and reduce the myocardial and vascular endothelial damage.

Extraordinary hot extreme in summer 2022 over the Yangtze River basin modulated by the La Nina condition under global warming

A widespread and prolonged hot extreme hit the Yangtze River basin in summer 2022,with 300 sites established new temperature records and nearly 96%stations endured more than 40 hot days.From the perspective of the combination effect of the global warming and La Nina condition,potential mechanisms of the hot extreme were investigated.Such a record-breaking hot extreme was caused by an extremely strong and westward-shifted western Pacific subtropical high(WPSH).The global warming effect contributed primarily to the abnormal hot days in the Yangtze River basin,coupled with the modulation of the La Nina condition.The sea surface temperature anomaly pattern under La Nina condition favored more convection activities over the western Pacific,encouraging an enhanced and westward-extended WPSH.In addition,an observation-based attribution analysis indicates that anthropogenic warming may increase the probability of such extensively persistent hot extremeby1.8 times.

新型冠状病毒(2019-nCoV)感染的肺炎诊疗快速建议指南(完整版)

2019新型冠状病毒(2019 novel coronavirus,2019-nCoV)感染的肺炎,因2019年12月发生在武汉的不明原因病毒性肺炎病例而被发现,并于2020年1月12日被世界卫生组织(World Health Organization,WHO)命名。在之后的一个月时间内,2019-nCoV在湖北省内外甚至其他国家传播造成了数以千计的病例出现,同时也引起了民众一定程度的恐慌。本指南的制订希望能够从疾病流行病学、病因学、诊断、治疗、护理、医院感染控制等方面给临床医生、社区居民等提供医疗护理及居家照护相关指导。

新型冠状病毒肺炎药物预防、诊断、治疗与出院管理临床指南计划书

本计划书为《新型冠状病毒(2019-nCoV)感染的肺炎诊疗快速建议指南(标准版)》更新版的研究方案。计划书涵盖指南制定方法学、指南的目标用户、指南的目标人群、利益冲突调查与声明、临床问题和结局指标的遴选与确定、证据的检索、合成与评价、证据与推荐意见分级标准、推荐意见的形成、指南的更新,并附录指南临床问题清单、文献检索策略及利益冲突调查表。

新型冠状病毒院内感染调研与分析工具的开发与验证

目的制定2019-nCoV院内感染调研与分析工具,并行初步验证。方法研究小组基于前期循证制定的"新型冠状病毒医护感染过程及防控调研问卷",主要通过细化问卷调研目的、建立问卷条目池、评估问卷的效度三个步骤进行改编。结果形成了新型冠状病毒院内感染调研与分析工具,包括行政后勤感染组、医护对照组、行政后勤对照组3个问卷。问卷内容与研究目标具有较高的一致性。行政后勤感染组问卷包括"确诊前"、"确诊后"2个领域的调查,其中,"确诊前"涉及感染原因分析、确诊前防控方案、确诊前防控知识、确诊前心理上对疫情的应对状态4个部分,共计16个条目;"确诊后"包括确诊后症状、确诊后治疗、感染后对周围环境和人造成的影响、确诊后心理、感染后防护认识5个方面,共计21个条目。医护对照组问卷涉及与是否感染有关的工作或生活行为、防控相关行为、防控相关知识、心理上对疫情的应对状态4个方面,共计29个条目。行政后勤对照组问卷涉及的领域与医护对照组问卷相同,共计20个条目。结论本研究完成了2019-nCoV院内感染调研与分析工具的制定,共涉及2019-nCoV感染医院非医护工作人员感染过程及防控调研——行政、后勤人员专用,2019-nCoV感染医护感染对照组调研问卷——医护对照组,2019-nCoV感染医护感染对照组调研问卷——行政后勤对照组3个问卷,问卷的信度和效度均可靠、可行性良好。

IL-6 Plays a Crucial Role in HBV Infection

Interleukin-6(IL-6),a cytokine mainly produced by activated monocytes,has broad pleiotropic actions that affect the functions of a variety of lymphoid cells.The roles of IL-6 in regulating immunity to infections are currently being defined.Remarkably,IL-6-mediated cellular and humoral immune responses play a crucial role in determining the outcome of viral infection.This article reviews the current knowledge on the critical role of IL-6 in hepatitis B virus(HBV)infection.As a competent intermediary,IL-6 derived from activated monocytes plays an important role in promoting lymphocytes responses that are essential for effective viral control.However,as a mediator of inflammation,IL-6 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury.Overall,the current data point to IL-6 as an immunoregulatory cytokine in HBV infection.Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-6 in HBV infection may prove to be an ordeal in the future,as they should foster the strengths of IL-6 while circumventing potential drawbacks.