Hemorrhagic transformation in patients with large-artery atherosclerotic stroke is associated with the gut microbiota and lipopolysaccharide

Hemorrhagic transformation is a major complication of large-artery atheroscle rotic stroke(a major ischemic stro ke subtype)that wo rsens outcomes and increases mortality.Disruption of the gut microbiota is an important feature of stroke,and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis.We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in largearte ry atheroscle rotic stro ke.An observational retrospective study was conducted.From May 2020 to September 2021,blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy,as well as 16 healthy controls.Patients with stro ke who developed hemorrhagic transfo rmation(n=15)were compared to those who did not develop hemorrhagic transformation(n=17)and with healthy controls.The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing.We also examined key components of the lipopolysaccharide pathway:lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transfo rmation group compared with the healthy controls.The patients with ischemic stro ke who developed hemorrhagic transfo rmation exhibited altered gut micro biota composition,in particular an increase in the relative abundance and dive rsity of members belonging to the Enterobacteriaceae family.Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transfo rmation group.lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14 concentrations were associated with increased abundance of Enterobacte riaceae.Next,the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model.In this model,transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide,lipopolysaccharide-binding protein,and soluble CD14.Ta ken togethe r,our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation.This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transfo rmation after stro ke.

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.

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.

Liver injury in COVID-19: Known and unknown

Since the first report of the coronavirus disease 2019(COVID-19)in December 2019 in Wuhan,China,the outbreak of the disease is currently continuously evolving.Previous studies have shown varying degrees of liver damage in patients with COVID-19.However,the exact causes of liver injury and the relationship between COVID-19 and liver injury is unclear.This article describes liver injury induced by COVID-19,analyzes its causes,and discusses the treatment and prognosis of liver damage in patients with COVID-19.

用于损耗型集成光子器件的相变材料评价标准和设计策略

相变材料(PCM)具有优异的光学性质,在多种集成光子器件中极具应用前景,如光存储器、光开关和光神经形态计算器件.然而,由于集成光子器件相变材料光学性能评价标准的缺乏,新型相变材料的设计主要依赖于研究者的研究经验.本文基于相变光子器件的性能需求,引入材料品质因子(FOM2=Δk/kamor)来评价相变材料的光学性能,建立了针对损耗调制型相变光子器件相变材料的光学性能评价标准.FOM值的大小代表相变材料在构建高性能相变光子器件中的应用潜力,FOM值越大,相变材料应用于光子器件的限制就越小.在此基础上,本文基于光学带隙理论,建立了相变材料光学参数与FOM值之间的关系,开发了三种基于GST的新型光学相变材料.结果表明,氮等非金属元素掺杂可以提高GST的FOM值,有利于开发低损耗、高调制空间的损耗型相变光子器件和大规模损耗型相变光子阵列.除了FOM之外,相变材料的结晶温度也会影响器件的编程功耗、循环寿命和稳定性,这要求我们在实际应用场景中根据器件的需求选择合适的相变材料.总之,本文为相变材料的光学性能提供了评价标准,促进了集成光子器件应用中相变材料的定制设计.

碘伏冲洗急性阑尾炎术后感染的16S rRNA基因及炎性因子表达水平

目的探讨碘伏冲洗急性阑尾炎术后感染患者的16S核糖体核糖核酸(16S rRNA)基因及炎性因子表达水平。方法选择2019年7月-2020年7月滨州市中心医院手术室50例行急性阑尾炎术后碘伏冲洗感染患者为感染组;50例行急性阑尾炎术后碘伏冲洗非感染患者为非感染组;选取同期50名健康成年人为对照组。取各组血液标本进行血培养,聚合酶链反应(PCR)进行DNA扩增和16S rRNA基因检测,比较各组PCR和血培养检测结果。采用放射免疫分析法检测标本中炎性因子白细胞介素-6(IL-6)、C-反应蛋白(CRP)和肿瘤坏死因子-α(TNF-α)水平,比较各组炎性因子差异。结果对照组50例血标本PCR扩增结果均为阴性。感染组中有18例患者出现一条DNA带,其中10例血培养结果为阳性,出现细菌增长,8例为阴性,未出现细菌增长。PCR扩增阳性结果36.00%高于血培养阳性结果20.00%(χ^(2)=6.349,P=0.012)。感染组及非感染组IL-6、CRP、TNF-α水平均高于对照组,且感染组IL-6、CRP、TNF-α水平高于非感染组,差异有统计学意义(P<0.05)。结论16S rRNA基因可对急性阑尾炎术后行碘伏冲洗的感染患者进行预警监测,感染患者血清IL-6、CRP、TNF-α水平较非感染患者显著升高。

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。

在SrTiO_(3)/SrRuO_(3)异质结忆阻器件中实现电阻态高保持性

忆阻器的阻变动态特性与生物突触的工作过程相似,是构建硬件人工神经网络突触器件的有力候选者之一.在人工神经网络中,尤其是对于推理过程,要求突触权重具有好的保持性.然而,许多忆阻器的电阻态随着时间的推移出现阻态漂移,特别是基于氧离子迁移的氧化物忆阻器尤为严重.在本工作中,我们研制了基于Pt/SrTiO_(3)/SrRuO_(3)异质结的忆阻器,器件表现出了非常好的保持性.通过对其电传输机制和界面微观结构的研究,发现在SrTiO_(3)/SrRuO_(3)界面形成了富含SrO的界面层,由于氧空位在该界面层迁移的势垒较高,因此该界面层可限制氧空位在外加电场撤去后的自扩散,进而提高了器件电阻态的保持性.基于可图案化的底部电极、线性电导调制和神经网络模拟的优异性能,该器件在硬件神经形态计算中具有潜在应用价值.

Automatic differentiation based discrete adjoint method for aerodynamic design optimization on unstructured meshes

A systematic methodology for formulating,implementing,solving and verifying discrete adjoint of the compressible Reynolds-averaged Navier-Stokes（RANS） equations for aerodynamic design optimization on unstructured meshes is proposed.First,a general adjoint formulation is constructed for the entire optimization problem,including parameterization,mesh deformation,flow solution and computation of the objective function,which is followed by detailed formulations of matrix-vector products arising in the adjoint model.According to this formulation,procedural components of implementing the required matrix-vector products are generated by means of automatic differentiation（AD） in a structured and modular manner.Furthermore,a duality-preserving iterative algorithm is employed to solve flow adjoint equations arising in the adjoint model,ensuring identical convergence rates for the tangent and the adjoint models.A three-step strategy is adopted to verify the adjoint computation.The proposed method has several remarkable features：the use of AD techniques avoids tedious and error-prone manual derivation and programming;duality is strictly preserved so that consistent and highly accurate discrete sensitivities can be obtained;and comparable efficiency to hand-coded implementation can be achieved.Upon the current discrete adjoint method,a gradient-based optimization framework has been developed and applied to a drag reduction problem.

肠道病毒71型2C蛋白多克隆抗体的制备及鉴定

目的制备肠道病毒71型(enterovirus 71,EV-A71)2C蛋白的多克隆抗体并测试抗体的应用效果。方法分析EV-A712C的抗原性,设计合成1条EV-A712C蛋白多肽,偶联钥孔血蓝蛋白KLH作为抗原,免疫新西兰大白兔。ELISA测定免疫效价,达到要求后,收集血清并纯化。利用ELISA、免疫印迹、免疫沉淀和免疫荧光法对纯化后的2C蛋白抗体进行鉴定。结果设计的2C蛋白肽段刺激新西兰大白兔产生了特异性抗体,免疫印迹、免疫沉淀和免疫荧光法证明制备的抗体可特异性识别并结合2C蛋白。结论成功获得了EV-A71的2C蛋白抗体,为进一步研究2C蛋白功能提供了有效工具。

Clinical features of 162 fatal cases of COVID-19:a multi-center retrospective study

Background:The coronavirus disease 2019(COVID-19)has affected approximately 2 million individuals worldwide;however,data regarding fatal cases have been limited.Objective:To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30,2019 and March 12,2020.Methods:The demographic data,signs and symptoms,clinical course,comorbidities,laboratory findings,computed tomographic(CT)scans,treatments,and complications of the patients with fatal cases were retrieved from electronic medical records.Results:The median patient age was 69.5(interquartile range:63.0–77.25)years,and 80%of the patients were over 61 years.A total of 112(69.1%)patients were men.Hypertension(45.1%)was the most common comorbidity,while 59(36.4%)patients had no comorbidity.At admission,131(81.9%)patients had severe or critical COVID-19,whereas 39(18.1%)patients with hypertension or chronic lung disease had moderate COVID-19.In total,126(77.8%)patients received antiviral treatment,while 132(81.5%)patients received glucocorticoid treatment.A total of 116(71.6%)patients were admitted to the intensive care unit(ICU),and 137(85.1%)patients received mechanical ventilation.Most patients received mechanical ventilation before ICU admission.Approximately 93.2%of the patients developed respiratory failure or acute respiratory distress syndrome.There were no significant differences in the inhospital survival time among the hospitals(P=0.14).Conclusion:Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes.The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan.

痘病毒E3泛素连接酶的研究进展

在病毒感染过程中,宿主主要通过抗病毒免疫反应阻止病毒入侵、复制扩增。病毒在长期的进化过程中也形成了多种逃逸宿主抗病毒免疫反应的机制,其中包括在痘病毒中发现的可以利用宿主细胞泛素系统的泛素连接酶,这些泛素连接酶可以在不同水平抑制宿主抗病毒防御机制,其对病毒的复制和传播均具有重要作用。根据结构特点痘病毒编码的E3泛素连接酶可以分为4类:MARCH结构域蛋白、P28/RING finger结构域蛋白、ANK repeat/F-box结构域蛋白、BTB/Kelch结构域蛋白等。本文着重阐述了痘病毒编码的具有E3泛素连接酶功能蛋白的研究进展。

Important scoring systems for assessing the severity of COVID-19 based on COVID-19-related deaths in Wuhan,China

Background:This study aimed to investigate the clinical characteristics of 21 deaths and evaluate potential factors affecting disease severity and mortality risk in patients with coronavirus disease(COVID-19).Methods:This retrospective analysis assessed clinical data of 21 patients who died owing to COVID-19.Disease severity and mortality risk were assessed using Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ);Sepsis-related Organ Failure Assessment(SOFA);multilobular infiltration,hypo-lymphocytosis,bacterial coinfection,smoking history,hypertension and age(MuLBSTA);and pneumonia severity index(PSI)scores.Results:The mean age of the patients was 66±14 years and 15(71.4%)patients were men.Sixteen(76.2%)patients had chronic medical illnesses.Twelve(57.1%)patients were overweight.Decreased lymphocyte proportions were observed in 17(81.0%)patients on admission.Elevated D-dimer levels were observed in 11(52.4%)patients,and the levels significantly increased when pneumonia deteriorated.The initial APACHE II and SOFA scores demonstrated that 18(85.7%)and 13(61.9%)patients,respectively,were in the middle-risk level.MuLBSTA and PSI scores after admission were associated with higher risks of mortality in 13(61.9%)patients.Most patients developed organ failure and subsequently died.Conclusions:Older,overweight,male patients with a history of chronic illnesses and continuously decreased lymphocyte proportions and increased D-dimer levels might have higher risks of death owing to COVID-19.The combination of general scoring(SOFA)and pneumonia-specific scoring(MuLBSTA and PSI)systems after admission might be sensitive in assessing the mortality risk of patients with COVID-19 who are in critical condition.