CPAL, as a New Mediator of Cardiomyocyte Metabolic Alterations and Pyroptosis, Regulates Myocardial Infarction Injury in Mice

Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.

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.

Methodological quality(risk of bias) assessment tools for primary and secondary medical studies: What are they and which is better?

Methodological quality(risk of bias)assessment is an important step before study initiation usage.Therefore,accurately judging study type is the first priority,and the choosing proper tool is also important.In this review,we introduced methodological quality assessment tools for randomized controlled trial(including individual and cluster),animal study,non-randomized interventional studies(including follow-up study,controlled before-and-after study,before-after/pre-post study,uncontrolled longitudinal study,interrupted time series study),cohort study,case-control study,cross-sectional study(including analytical and descriptive),observational case series and case reports,comparative effectiveness research,diagnostic study,health economic evaluation,prediction study(including predictor finding study,prediction model impact study,prognostic prediction model study),qualitative study,outcome measurement instruments(including patient-reported outcome measure development,content validity,structural validity,internal consistency,cross-cultural validity/measurement invariance,reliability,measurement error,criterion validity,hypotheses testing for construct validity,and responsiveness),systematic review and meta-analysis,and clinical practice guideline.The readers of our review can distinguish the types of medical studies and choose appropriate tools.In one word,comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

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.

Optimal Nonlinear Distance Toll for Cordon-Based Congestion Pricing Considering Equity Issue

In order to address the optimal distance toll design problem for cordon-based congestion pricing incorporating the issue of equity,this paper presents a toll user equilibrium( TUE) model based on a transformed network with elastic demand,to evaluate any given toll charge function. A bi-level programming model is developed for determining the optimal toll levels,with the TUE being represented at the lower level.The upper level optimizes the total equity level over the transport network,represented by the Gini coefficient,where a constraint is imposed to the total travel impedance of each OD pair after the levy. A genetic algorithm( GA) is implemented to solve the bi-level model,which is verified by a numerical example.

医学专业课程思政实践探索与思考——以武汉大学“课程思政”示范课程“循证医学”为例

课程思政建设是全面提高人才培养质量的重要任务。在医学专业课程中开展课程思政对于培养德才兼备的医学生、提高医学人才培养质量具有重要意义。建立健全课程思政体系、完善课程思政质量评价机制、加强课程思政内容建设、提升教师思政能力及发挥学生主动性可以有效促进医学专业课程思政的开展。本文以武汉大学“课程思政”示范课程“循证医学”为例,探索并思考了课程思政融入医学专业教学的实施路径与方法。

Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability

Background:Melatonin,a natural hormone secreted by the pineal gland,has been reported to exhibit antitumor properties through diverse mechanisms of action.However,the oncostatic function of melatonin on esophageal squamous cell carcinoma(ESCC) remains elusive.This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.Methods:ESCC cell lines treated with or without melatonin were used in this study.In vitro colony formation and 5-Ethynyl-2’-deoxyuridine(EdU) incorporation assays,and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells.RNA-seq,qPCR,Western blotting,recombinant lentivirus-mediated target gene overexpression or knockdown,plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth.IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes’ expression and prognosis of ESCC.Results:Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7(HDAC7),c-Myc and ubiquitin-specific peptidase 10(USP10) in ESCC cells(P<0.05).The expressions of HDAC7,c-Myc and USP10 in tumors were significantly higher than the paired normal tissues from 148 ESCC patients(P<0.001).Then,the Kaplan-Meier survival analysis suggested that ESCC patients with high HDAC7,c-Myc or USP10levels predicted worse overall survival(log-rank P<0.001).Co-IP and Western blotting further revealed that HDAC7physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription.Notably,our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth,and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells.Additionally,we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Conclusions:Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth,and provides the reference for identifying biomarkers and therapeutic targets for ESCC.

The fabrication of hydroxyapatite mineralized hydrogels for bone tissue engineering

Bone is a complex but orderly mineralized tissue with hydroxyapatite(HA)as the inorganic phase and collagen as the organic phase.Inspired by natural bone tissues,HA-mineralized hydrogels have been widely designed and used in bone tissue engineering.HA is majorly utilized for the treatment of bone defects because of its excellent osteoconduction and bone inductivity.Hydrogel is a three-dimensional hydrophilic network structure with similar properties to the extracellular matrix(ECM).The combination of HA and hydrogels produces a new hybrid material that could effectively promote osteointegration and accelerate the healing of bone defects.In this review,the structure and growth of bone and the common strategies used to prepare HA were briefly introduced.Importantly,we discussed the fabrication of HA mineralized hydrogels from simple blending to in situ mineralization.We hope this review can provide a reference for the development of bone repair hydrogels.

Optical two-dimensional coherent spectroscopy of excitons in transition-metal dichalcogenides

Exciton physics in atomically thin transition-metal dichalcogenides(TMDCs)holds paramount importance for fundamental physics research and prospective applications.However,the experimental exploration of exciton physics,including excitonic coherence dynamics,exciton many-body interactions,and their optical properties,faces challenges stemming from factors such as spatial heterogeneity and intricate many-body effects.In this perspective,we elaborate upon how optical two-dimensional coherent spectroscopy(2DCS)emerges as an effective tool to tackle the challenges,and outline potential directions for gaining deeper insights into exciton physics in forthcoming experiments with the advancements in 2DCS techniques and new materials.

“互联网+”新型教学模式形成性评价体系构建及其应用于循证医学课程的思考

“互联网+”给医学教育带来巨大挑战,融入信息技术的新型教学活动应用日益广泛,它们具有较强的开放性、自主性和灵活性,如何强化对课程教学过程的监督、管理和评估,已成为推动教学改革的难点。作为课程教学评价的重要方式之一,形成性评价在“教学-反馈-改进”过程中起着重要作用。本文分析了医学教育领域“互联网+”教学模式及其形成性评价体系特点,提出了评价体系的建设方向及改革着力点,结合武汉大学循证医学混合式教学的授课经验,以该课程为例提出了形成性评价体系建设思路。期望能与同行相互探讨,共同推动信息技术与循证医学类课程的深度融合,充分发挥其在医学生循证医学能力培养中的作用。

循证医学课程体系的建设与实践--以武汉大学为例

循证医学教育是国际及我国医学教育的基本要求内容,其目的在于培养具备解决临床实际问题能力、批判性思维能力、创新能力等的医学人才。武汉大学自2004年首次开设循证医学课程至今,进行了全方位、系统性的探索与实践,完成了教研室的创建、师资力量的构建、课程体系的打造,实现了医学专业学生全覆盖,有效地将循证医学教育特色融入新时代医学生培养进程中。本文对武汉大学循证医学课程体系定位及建设思路进行介绍,特别是对创新“1+4”的课程教学模式、建立全过程“教”与“学”的评价、创新师资力量的培养与传承三大具体措施进行了总结,以期为我国循证医学教育及其教学改革提供参考,服务于培养符合时代需求的医学人才。

医学生对循证医学课程思政认知与态度的横断面研究

目的调查医学生对课程思政的态度和思政元素的需求,贯彻三全育人理念,为医学类课程思政设计和教学改革提供参考。方法选择武汉大学第二临床学院2021-2022学年第一学期选修循证医学的研究生,设计“课程思政认知与态度”问卷,就学生对思政内容的要求和评价进行调查,利用SPSS 22.0软件进行数据录入与分析。结果共纳入138名学生,其中83.33%的学生对课程思政融入循证医学专业课感兴趣,学生对专业课中思政内容的兴趣越大,越认可授课教师在理想信念(r=0.33,P<0.001)、仁爱之心(r=0.28,P<0.001)、道德情操(r=0.24,P=0.005)和扎实学识(r=0.21,P=0.020)方面对自己的影响。学生主要关注的课程思政元素是专业知识与思政相结合的内容(51.45%),并希望思政内容能有机融入、不要太“刻意”(84.06%)。结论大部分医学生对课程思政融于专业课持肯定态度。自然、适度、适时地融入思政元素并采用创新的教学方法,可获得更好的效果。

混合式教学在我国临床医学专业教学中应用效果的系统评价和Meta分析

目的采用Meta分析方法探讨混合式教学在我国临床医学专业教学中的应用效果,为培养临床医学人才、提高医学教育质量提供参考。方法在PubMed、中国知网(CNKI)、万方(WanFang Data)和中国生物医学文献数据库(SinoMed)中检索有关临床医学专业混合式教学的文献,由两位研究者独立进行文献筛选、资料提取及质量评价,采用Stata12.0软件进行Meta分析。通过亚组分析探讨异质性来源、敏感性分析探讨单个研究对合并效应量的影响。结果共纳入66篇文献,纳入研究间的异质性较大,基于随机效应模型的Meta分析结果显示,在理论知识[SMD=1.73,95%CI(1.32,2.15),P<0.05]、实践/操作技能[SMD=1.28,95%CI(0.81,1.75),P<0.05]、满意度[RR=1.35,95%CI(1.23,1.49),P<0.05]方面,混合式教学均优于传统教学;未发现不同学历层次学生在理论知识、实践/操作技能方面存在差异;本科学生在理论知识[SMD=1.79,95%CI(1.27,2.31),P<0.001]、实践/操作技能[SMD=1.62,95%CI(1.12,2.13),P<0.001]方面,混合式教学均优于传统教学;专科学生在理论知识[SMD=1.28,95%CI(0.60,1.96),P<0.001]方面,混合式教学优于传统教学,而实践/操作技能[SMD=-0.11,95%CI(-2.48,2.26),P=0.929]方面差异无统计学意义。结论相较于传统教学,混合式教学对提高我国临床医学专业学生理论知识和实践/操作技能效果更佳,且满意度更高,提示可以充分发挥混合式教学的优势,助力医学教育改革及临床医学人才的培养。

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

A qualitative study on nurses'reactions to inpatient suicide in a general hospital

Aims:To explore the impact of inpatient suicides on nurses working in front-line,the patterns of regulation and their needs for support.Methods:Data were collected through purposive sampling by conducting semi-structured and individual in-depth interviews in a tertiary referral hospital in China.Colaizzi's sevenstep phenomenological method was simultaneously used by two interviewers.Results:Reactions to inpatient suicides revealed three central themes:(1)inpatients were highly likely to commit suicide,(2)inpatient suicide was difficult to prevent,and(3)nurses lacked the necessary suicide prevention skills.Psychological responses mainly included shock and panic,self-accusation or guilt,sense of fear,and frustration.The impacts on practice were stress,excessive vigilance,and burnout.Avoidance and sharing of feelings played key roles in the regulation patterns of nurses.Conclusions:Nurses who experienced inpatient suicide became stressed.Effective interventions must be implemented to improve the coping mechanisms of nurses against the negative consequences of inpatient suicide.The findings of this study will allow administrators to gain insight into the impacts of inpatient suicides on nurses in general hospitals.Such information can be used to develop effective strategies and provide individual support and ongoing education.Consequently,nurses will acquire suicide prevention skills and help patients achieve swift recovery.

Five High-risk Factors for Inpatient Suicide

Objective:The aim of this study was to identify the risk factors for inpatient suicide in a general hospital.Methods:Thirty suicide victims were drawn from the adverse event reports of suicidal acts during hospitalization in a general hospital from 2008 to 2014.Data were gathered from a focus group interview of 6 medical staff who had experienced inpatient suicide.Interpretative phenomenological analysis was used to analyze the data.Results:Five main themes regarding high-risk factors for inpatient suicide emerged from this study:mental disorders,diseases,the source of money to meet medical expenses,social support,and the hospital environment.Patients with mental disorders were at a high risk of suicide.Having a serious disease paying high medical expenses alone,the loss of social support and unsafe hospital environments were also associated with an increased risk of suicide.Conclusions:This study puts forward different perspectives on the reasons that inpatients commit suicide and corresponding preventive measures based on these 5 main themes that could be implemented to avoid or reduce suicidal acts among inpatients during hospitalization.

Erratum:A Search for Solar Axions and Anomalous Neutrino Magnetic Moment with the Complete PandaX-Ⅱ Data[CHIN.PHYS.LETT.38(2021)011301]

In our published letter,[1]we have identified a minor error in Figs.2 and 3.Instead,we have 2111 events in these two plots with 646,249,382,and 834 events in Run 9(20.0 ton·day),Run 10(19.4 ton·day),Run 11–1(24.2 ton·day),and Run 11–2(37.1 ton·day).The mistake is due to an incorrect application of a small energy non-linearity(known as the BLS non-linearity)in making plots,but has no impact to the final results.Figures 2 and 3 are now updated in this note.

Guben Tongluo Formula Protects LPS-induced Damage in Lamina Propria B Lymphocytes Through TLR4/MyD88/NF-κB Pathway

Objective The main pathological feature of immunoglobulin A nephropathy(IgAN),an autoimmune kidney disease,is the deposition of IgA immune complexes,accompanied by mesangial cell proliferation and elevated urine protein.The Guben Tongluo formula(GTF)is a traditional Chinese medicine prescription,which has predominant protective effects on IgAN.However,the therapeutic mechanism of the GTF in IgAN remains elusive.The present study aimed to determine the effects of GTF in treating IgAN via regulating the TLR4/MyD88/NF-κB pathway.Methods In the present study,lamina propria B lymphocytes were treated with different concentrations of lipopolysaccharide(LPS)(0,1,5,10 and 20 ng/mL).Flow cytometry was used to define positive CD86+CD19+cells.CCK-8 assay was used to examine cell proliferation.RNAi was used to induce TLR4 silencing.qRT-PCR and Western blotting were used to determine gene expression.Results It was found that the LPS dose-dependently increased the content of IgA and galactose-deficient IgA1(Gd-IgA),the levels of TLR4,Cosmc,MyD88 and phosphorylated(p)-NF-κB,and the ratio of CD86+CD19+and IgA-producing B cells.However,the TLR4 knockdown reversed the role of LPS.This suggests that TLR4 mediates the effects of LPS on lamina propria B lymphocytes.Furthermore,the GTF could dose-dependently counteract the effects of LPS and TLR4 overexpression on lamina propria B lymphocytes through the TLR4/MyD88/NF-κB pathway.Conclusion Collectively,these results demonstrate that the GTF can regulate the TLR4/MyD88/NF-κB pathway to treat IgAN model lamina propria B lymphocytes stimulated by LPS.

One-dimensional ZnSe@N-doped carbon nanofibers with simple electrospinning route for superior Na/K-ion storage

One-dimensional carbon nanofibers are widely applied as anode material in the energy storage field due to its unique structure and high conductivity. In this work, one-dimensional ZnSe@N-doped carbon nanofibers(ZnSe@NC NFs) are successfully synthesized by electrospinning and annealed without extra troublesome conditions. ZnSe nanocrystals are enfolded in the N-doped carbon nanofibers, which can act as a protective layer to avoid the volume expansion of active material and promote ion transport during the cycling process. More importantly, the as-synthesized ZnSe@NC NFs are served as the anode material and display the admirable storage properties for Na/K-ion batteries. The one-dimensional Zn Se@NC NFs material shows the high capacity of 237 mAh/g for Na-ion batteries at a current density of 1 A/g for 2000cycles. Meanwhile, it also delivers a high discharge capacity of 337 mAh/g for K-ion batteries at 0.2 A/g for 300 cycles. Additionally, it is confirmed that the pseudocapacitive contribution of the nano-structure material is up to 54.5% at a scan rate of 0.6 m V/s through the cyclic voltammetry(CV) measurement in K-ion batteries.

Influence of plasma on the densification mechanism of SPS under multi-field effect

The densification mechanism of an Fe-based alloy powder containing tiny oxide particles under the synergic multi-field effect of spark plasma sintering(SPS) was investigated. Metallographic microscopy and scanning electron microscopy were used to observe the morphology of samples sintered at different temperatures, and the temperature distribution in an individual spherical powder particle during sintering was calculated in consideration of the influence of plasma, which was qualified and quantified through the analysis of the U-I curve. The plasma was observed to play a substantial role in activating and heating the samples at the very early stage of sintering, whereas the joule-heat effect played a dominant role during sintering. Moreover, the plasma also facilitated the diffusion and migration of materials for neck formation.