Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2(SARS-CoV-2)specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies(mAbs)in the treatment of coronavirus infectious disease 2019(COVID-19).The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied.Immunoglobulin M(IgM)appeared earlier and lasted for a short time,while immunoglobulin G(IgG)appeared later and lasted longer.IgM tests can be used for early diagnosis of COVID-19,and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons.The combination of antibody testing and nucleic acid testing,which complement each other,can improve the diagnosis rate of COVID-19.Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients.COVID-19 convalescent plasma,highly concentrated immunoglobulin,and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products.Due to the continuous emergence of mutated strains of the novel coronavirus,especially omicron,its immune escape ability and infectivity are enhanced,making the effects of authorized products reduced or invalid.Therefore,the optimal application of anti-SARS-CoV-2 antibody products(especially anti-SARS-CoV-2 specific mAbs)is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Efficacy of continuous arterial perfusion chemotherapy combined with transarterial chemoembolization regional arterial thermal perfusion in the treatment of pancreatic cancer with liver metastases

Background:The aim of the study was to investigate the efficacy of continuous transcatheter arterial infusion chemotherapy combined with transarterial chemoembolization(TACE)for the treatment of advanced pancreatic cancer with liver metastasis.Methods:Sixty patients with advanced pancreatic cancer and liver metastases were enrolled in this study.In the treatment group,31patients underwent continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial thermal perfusion,whereas 29 patients included in the control group received intravenous chemotherapy with gemcitabine and S-1.All patients received maintenance chemotherapy with S-1 after 4 cycles of the study regimen.Treatment efficacy,quality of life,survival,and toxicity were evaluated.Results:Efficacy was better in the treatment group than in the control group,as reflected by the objective remission,partial remission,and disease progression rates(all P<0.05).The Eastern Cooperative Oncology Group and Numerical Rating Scale pain scores were also higher in the treatment group(both P<0.05).In survival analysis,the 1-year overall survival rates in the treatment and control groups were64.516%and 10.345%,respectively,whereas the median overall survival times were 16 and 6 months,respectively(both P<0.05).The6-month progression-free survival rates in the treatment and control groups were 77.419%and 13.790%,respectively,and the median progression-free survival times were 12 and 3 months,respectively(both P<0.05).The rates of hematological and nonhematological toxicological adverse effects were also lower in the treatment group(both P<0.05).Although the rate of liver dysfunction was higher in the treatment group,this finding had no adverse effects on prognosis.Conclusions:Continuous transcatheter arterial infusion chemotherapy combined with TACE regional arterial perfusion chemotherapy resulted in better efficacy and safety outcomes in patients with pancreatic cancer and liver metastasis,suggesting its utility as a reference method for the clinical treatment of advanced pancreatic cancer.

多原发恶性肿瘤——乳腺肺四重癌1例报告并文献复习

目的:探讨多原发恶性肿瘤的发病特点,提高对该肿瘤的认识,减少临床漏诊误诊,延误治疗。方法:分析我院1例乳腺肺四原发恶性肿瘤的诊治经过,并结合文献进行回顾总结。结果:该例首患乳腺癌,17年后再同时患肺乳腺三重癌,最终确诊为乳腺肺四原发恶性肿瘤。结论:多原发恶性肿瘤发病与宿主自身状况、环境、遗传、治疗等多因素有关,临床容易漏诊或误诊为复发癌和转移癌,治疗和预后与单原发肿瘤一样,异时性好于同时性。

电商大数据网络指数统计建模与分析

本文首先简述电商大数据时代的现状,选取百度指数和阿里指数,对其概念进行说明。基于智能手机行业的阿里指数分析了自2016年1月1日至2016年3月3日的数据,运用SAS软件编程,研究了序列的平稳性和随机性,并对得到的两个平稳非白噪声序列进行模型拟合和预测,最后得出模型表达式并计算了预测误差。结果发现,所得出的结论能为1688采购商和1688供应商提供一定的参考价值。

长江中下游六省大气甲烷柱浓度时空分布

甲烷(CH4)是造成气候变暖的主要温室气体之一。为了了解长江中下游水稻种植区CH4浓度的分布情况,本次研究基于温室气体观测卫星(greenhouse gases observing satellite,GOSAT)和大气红外探测仪(atmospheric infrared sounder,AIRS)卫星反演的数据产品,对我国长江中下游六省大气CH4柱浓度的时空分布特征进行了研究。研究结果表明,由GOSAT反演的长江中下游六省大气CH4浓度呈逐年增长趋势,其年均浓度由2011年的1817×10^(−9)增长至2018年的1875×10^(−9),高于东三省、华北平原和全国平均水平。区域平均年增长量为8.2×10^(−9) a^(−1)。各省年际增长幅度略有差异,纬度偏低的江西、湖南和浙江三省大气CH4浓度高且增长量偏大,纬度偏高的湖北、安徽和江苏三省大气CH4浓度略低且增长量偏小。长江中下游六省大气CH4呈现较强的季节变化特征,湖北、湖南、江西和浙江峰值出现在9月,安徽、江苏峰值出现在8月。垂直方向上长江中下游六省CH4浓度随气压降低,浓度逐渐减小,呈现出明显的季节变化特征,近地面层GOSAT反演的最高值出现在夏季,最低值出现在春季;高层最高值出现在秋季,最低值出现在春季。AIRS反演的大气CH4浓度空间分布上北高南低,与GOSAT反演结果不一致,可能由于AIRS主要反映了对流层中层大气状况而GOSAT更多的反映了近地面层大气CH4的变化。其垂直方向上呈现高度越高,浓度越低,不同高度上秋季浓度均最高。

Influence of heat treatment on microstructure and mechanical properties of FeCrNi coating produced by laser cladding

The FeCrNi alloy powders were used on the dovetail groove of FV520B steel to fabricate the multilayer laser cladding layers. The effects of heat treatment on the microstructure and mechanical properties of FeCrNi layers were investigated. The results showed that the heat treatment at the temperature ranged from 1073 to 1273 K refined the grains of the substrate materials and removed the soft zone of hardness between the fused zone (FZ) and base material (BM) effectively mainly due to a secondary quench of heat treatment. When the temperature of heat treatment was 1073 K, the maximum ultimate tensile strength (UTS) values of the laser cladding component were obtained. However, the heat treatment at high temperature had a bad effect on wear resistance of coatings at some extent.

Nested case-control study of multiple serological indexes and Brighton pediatric early warming score in predicting death of children with sepsis

BACKGROUND Currently, it is difficult to predict the complications of children at the early stage of sepsis. Brighton pediatric early warning score(PEWS) is a disease risk assessment system that is simple and easy to operate, which has good sensitivity and specificity in disease recognition among children. Because detection indicators vary widely in children, a single indicator is difficult to assess the posttreatment status of children with sepsis.AIM To investigate the relationship between serological markers, Brighton PEWS, and death in children with sepsis after treatment.METHODS A total of 205 children diagnosed with sepsis at our hospital were enrolled. The baseline data, serum scores, and PEWS scores were recorded. In the nested casecontrol study, children who died during the study period were included in an observation group. According to the matching principle, the children who were not dead in the same cohort were included in a control group. The influencing factors of death in children with sepsis after treatment and the value of each evaluation index in predicting the prognosis of children were analyzed.RESULTS A total of 96 children were enrolled in the study, including 48 each in the observation group and the control group. Multivariate logistic regression analysis indicated that antibacterial treatments within 1 h(P = 0.017), shock(P = 0.044),multiple organ dysfunction syndrome(MODS)(P = 0.027), serum procalcitonin(PCT)(P = 0.047), serum albumin(ALB)(P = 0.024), and PEWS(P = 0.012) were independent risk factors for the death of children with sepsis. The area under the curve of the combination of ALB, PCT, and PEWS to predict the death in children with sepsis was the highest(0.908).CONCLUSION Antibacterial treatments within 1 h, shock, MODS, PCT, ALB, and PEWS are independent risk factors for the death of children with sepsis. The predictive accuracy of the combination of PCT, ALB, and PEWS for the prognosis of children with sepsis is the best.

Effect of Annealing Time on the Dielectric Properties of BaMn₃Ti₄O_14.25Pellets by Spark Plasma Sintering

In this paper, the effects of annealing time on the dielectric properties of the Spark Plasma Sintered (SPS) BaMn3Ti4O14.25 pellets were detail studied by the crystal structure analysis, micro structural observation and electrical properties research. The results showed that long annealing time was beneficial to the recovery of crystal structure damage caused by SPS, the formation of a reoxidation layer at the surface of grains and decreasing of the electrically insulating phase. All of these resulted in an increase in dielectric constant and loss, and a reduction in breakdown voltage.

三维适形立体定向γ射线治疗老年中晚期胰腺癌39例的近期疗效

目的探讨三维适形立体定向γ射线(体部γ刀)治疗老年中晚期胰腺癌的近期疗效。方法对中国人民解放军第九四医院2011年7月至2016年10月使用OUR-QGD型体部γ刀治疗系统治疗的39例老年中晚期胰腺癌患者临床资料进行回顾性分析。OUR-QGD型体部γ刀治疗方法:50%~70%的等剂量曲线包绕计划靶区(PTV),照射剂量2.5~4.5Gy·次-1,1次·d-1,5次·周-1,共8~14次,DT30~45Gy。结果治疗8周后复查CT或MRI评价疗效,39例患者完全缓解4例(10.25%)、部分缓解25例(64.10%)、病情稳定7例(17.94%)、病变进展3例(7.69%),总有效率为74.35%。结论体部γ刀治疗老年中晚期胰腺癌近期疗效显著,可改善营养状态、缓解疼痛、提高生活质量,可作为非手术治疗之外的首选。

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be compromised.Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.Cathepsin L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response.Here,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and CAPN1.The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1.Both showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various cells.Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance.Moreover,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in mice.In addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model.And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia.Taken together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Rh(Ⅲ)-catalyzed late-stage C-H alkenylation and macrolactamization for the synthesis of cyclic peptides with unique Trp(C7)-alkene crosslinks

Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.

Stability Analysis and Order Improvement for Time Domain Differential Quadrature Method

The differential quadrature method has been widely used in scientific and engineering computation.However,for the basic characteristics of time domain differential quadrature method,such as numerical stability and calculation accuracy or order,it is still lack of systematic analysis conclusions.In this paper,according to the principle of differential quadrature method,it has been derived and proved that the weighting coefficients matrix of differential quadrature method meets the important V-transformation feature.Through the equivalence of the differential quadrature method and the implicit Runge-Kutta method,it has been proved that the differential quadrature method is A-stable and s-stage s-order method.On this basis,in order to further improve the accuracy of the time domain differential quadrature method,a class of improved differential quadrature method of s-stage 2s-order has been proposed by using undetermined coefficients method and Pad´e approximations.The numerical results show that the proposed differential quadrature method is more precise than the traditional differential quadrature method.