Roles of host proteases in the entry of SARS-CoV-2

The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.

Mutations in spike protein and allele variations in ACE2 impact targeted therapy strategies against SARS-CoV-2

Coronavirus disease 2019(COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2(SARS-Co V-2), has spread rapidly worldwide with high rates of transmission and substantial mortality. To date, however, no effective treatments or enough vaccines for COVID-19 are available. The roles of angiotensin converting enzyme 2(ACE2) and spike protein in the treatment of COVID-19 are major areas of research. In this study, we explored the potential of ACE2 and spike protein as targets for the development of antiviral agents against SARS-Co V-2. We analyzed clinical data, genetic data, and receptor binding capability.Clinical data revealed that COVID-19 patients with comorbidities related to an abnormal reninangiotensin system exhibited more early symptoms and poorer prognoses. However, the relationship between ACE2 expression and COVID-19progression is still not clear. Furthermore, if ACE2 is not a good targetable protein, it would not be applicable across a wide range of populations. The spike-S1 receptor-binding domain that interacts with ACE2 showed various amino acid mutations based on sequence analysis. We identified two spike-S1 point mutations(V354 F and V470 A) by receptorligand docking and binding enzyme-linked immunosorbent assays. These variants enhanced the binding of the spike protein to ACE2 receptors and were potentially associated with increased infectivity. Importantly, the number of patients infected with the V354 F and V470 A mutants has increased with the development of the SARS-Co V-2 pandemic. These results suggest that ACE2 and spike-S1 are likely not ideal targets for the design of peptide drugs to treat COVID-19 in different populations.

Highly Sensitive Poly-N-isopropylacrylamide Microgel-based Electrochemical Biosensor for the Detection of SARS-COV-2 Spike Protein

Objective Late 2019 witnessed the outbreak and widespread transmission of coronavirus disease 2019(COVID-19),a new,highly contagious disease caused by novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Consequently,considerable attention has been paid to the development of new diagnostic tools for the early detection of SARS-CoV-2.Methods In this study,a new poly-N-isopropylacrylamide microgel-based electrochemical sensor was explored to detect the SARS-CoV-2 spike protein(S protein)in human saliva.The microgel was composed of a copolymer of N-isopropylacrylamide and acrylic acid,and gold nanoparticles were encapsulated within the microgel through facile and economical fabrication.The electrochemical performance of the sensor was evaluated through differential pulse voltammetry.Results Under optimal experimental conditions,the linear range of the sensor was 10-13-10-9 mg/m L,whereas the detection limit was 9.55 fg/mL.Furthermore,the S protein was instilled in artificial saliva as the infected human saliva model,and the sensing platform showed satisfactory detection capability.Conclusion The sensing platform exhibited excellent specificity and sensitivity in detecting spike protein,indicating its potential application for the time-saving and inexpensive detection of SARS-CoV-2.

<i>Morinda citrifolia</i>(Noni) Fruit Juice Inhibits SARS-CoV-2 Spike Protein Binding of Angiotensin-Converting Enzyme 2 (ACE2)

COVID-19 is a global pandemic that has claimed millions of lives. This disease is caused by a coronavirus, SARS-CoV-2, which requires the binding of its spike protein to angiotensin-converting enzyme 2 (ACE2) for infection of the host cell. Morinda citrifolia (noni) fruit juice has antiviral activity that involves enhancement of immune system function. SARS-CoV-2 spike-ACE2 interaction experiments were carried out to further investigate the antiviral properties of noni juice and its major iridoids. Noni juice inhibited binding by approximately 69%. Scandoside was the most active of the three iridoids evaluated, reducing average spike protein-ACE2 interaction by 79.25%. The iridoids worked synergistically towards inhibiting spike protein binding when assayed together, improving activity by more than 22% above the expected level. But the modest activity of the most abundant iridoid, deacetylasperulosidic acid, indicates that other phytochemicals (i.e. scopoletin, quercetin, rutin and kaempferol) are also involved. Our results suggest that the presence of several biological active phytochemicals in noni juice enhances resistance to SARS-CoV-2 by interfering with its ability to bind ACE2. This is a new and significant anti-viral mechanism of noni juice that does not directly involve its immunomodulatory properties.

Universal COVID-19 Vaccine Targeting SARS-CoV-2 Envelope Protein

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had caused over 382 million cases and over 2.7 million deaths globally as of 23 March 2021. By that date, at least 10 SARS-CoV-2 variants had emerged. The transmissibility and lethality of the variants are higher than those of the Wuhan reference strain. Therefore, a universal vaccine for the reference strain and all variants (present and future) is indispensable. The coronavirus envelope (E) protein is an integral membrane protein crucial to the viral lifecycle and the pathogenesis of coronaviruses. The SARS-CoV-2 E protein has a postsynaptic density protein 95/Drosophila disc large tumor suppressor/zonula occludens-1 (PDZ) binding motif (PBM), and its interaction with PDZ-domain-2 of the human tight junction protein may interrupt the integrity of lung epithelium. Furthermore, the SARS-CoV-2 E protein itself is a homopentameric cation channel viroporin, which may be involved in viral release. This protein is thus a potential target for the development of a universal COVID-19 vaccine, because of its highly conserved amino acid sequence. The variant mutations occur mainly in the spike protein, and conservation of E protein remained in most Variants of Concern (VOC). Only one of the extant VOC have mutations in the E protein that P71L mutation occurs in the South African variant 501Y.V2 (B.1.351). If a vaccine is designed to target E protein, two scenarios are possible: 1) SARS-CoV-2 maintains a highly conserved E protein amino acid sequence, rendering the virus consistently or permanently susceptible to the vaccine;or 2) the E protein mutates and new variants evolve accordingly. In scenario 2, the tertiary structure and function of the E protein homopentameric cation channel viroporin, PBM, or other aspects affecting pathogenicity would be attenuated. Either scenario would thus ameliorate the pandemic. I therefore propose that a vaccine targeting the SARS-CoV-2 E protein would be effective against the Wuhan reference strain and all current and future SARS-CoV-2 variants. Efforts to create E protein-based vaccines are ongoing. Further research and clinical trials are needed to realize this universal COVID-19 vaccine.

脂质体包被SARS-CoV-2 N基因的候选DNA疫苗转染人源细胞效率研究

利用脂质体包被含有SARS-CoV-2核衣壳蛋白(nucleocapsid protein;N)基因的候选DNA疫苗,并检测其在人源细胞293T中的转染效率.将SARS-COV-2 N基因克隆入真核表达载体pcDNA3.1,DNA测序及转染后的质谱测序证明能够表达正确蛋白.利用脂质体包被pcDNA3.1-SARS-COV-2-N基因,并进行超离纯化、核酸电泳、透射电镜等检测发现形成50~100 nm的脂质体纳米颗粒,定量后将纳米颗粒转染293T细胞,并对比脂质体转染与FUGENE~?HD试剂转染效果,表明制备的候选重组脂质体DNA疫苗能够形成稳定的纳米颗粒,并可在人源细胞293T中高效表达.

Structural basis of SARS-CoV-2 3CL^pro and anti-COVID-19 drug discovery from medicinal plants

The recent pandemic of coronavirus disease 2019(COVID-19)caused by SARS-CoV-2 has raised global health concerns.The viral 3-chymotrypsin-like cysteine protease(3CL^pro)enzyme controls coronavirus replication and is essential for its life cycle.3CL^pro is a proven drug discovery target in the case of severe acute respiratory syndrome coronavirus(SARS-CoV)and Middle East respiratory syndrome coronavirus(MERS-CoV).Recent studies revealed that the genome sequence of SARS-CoV-2 is very similar to that of SARS-CoV.Therefore,herein,we analysed the 3CL^pro sequence,constructed its 3D homology model,and screened it against a medicinal plant library containing 32,297 potential anti-viral phytochemicals/traditional Chinese medicinal compounds.Our analyses revealed that the top nine hits might serve as potential anti-SARS-CoV-2 lead molecules for further optimisation and drug development process to combat COVID-19.

Charge‑Transfer Resonance and Electromagnetic Enhancement Synergistically Enabling MXenes with Excellent SERS Sensitivity for SARS‑CoV‑2 S Protein Detection

The outbreak of coronavirus disease 2019 has seriously threatened human health.Rapidly and sensitively detecting SARSCoV-2 viruses can help control the spread of viruses.However,it is an arduous challenge to apply semiconductor-based substrates for virus SERS detection due to their poor sensitivity.Therefore,it is worthwhile to search novel semiconductor-based substrates with excellent SERS sensitivity.Herein we report,for the first time,Nb2C and Ta2C MXenes exhibit a remarkable SERS enhancement,which is synergistically enabled by the charge transfer resonance enhancement and electromagnetic enhancement.Their SERS sensitivity is optimized to 3.0×10^6 and 1.4×10^6 under the optimal resonance excitation wavelength of 532 nm.Additionally,remarkable SERS sensitivity endows Ta2C MXenes with capability to sensitively detect and accurately identify the SARS-CoV-2 spike protein.Moreover,its detection limit is as low as 5×10^−9 M,which is beneficial to achieve real-time monitoring and early warning of novel coronavirus.This research not only provides helpful theoretical guidance for exploring other novel SERS-active semiconductor-based materials but also provides a potential candidate for the practical applications of SERS technology.

Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2

The outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a serious global health threat.This raises an urgent need for the development of effective drugs against the deadly disease.SARS-CoV-2 non-structural protein 14(NSP14)carrying RNA cap guanine N7-methyltransferase and 30-50 exoribonuclease activities could be a potential drug target for intervention.NSP14 of SARS-CoV-2 shares 98.7%of similarity with the one(PDB 5NFY)of acute respiratory syndrome(SARS)by ClustalW.Then,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14(PDB 5NFY)as template for virtual screening.Based on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further evaluation.Based on the 5 ns MD simulation trajectory,binding free energy(DG)was calculated by MM/GBSA method.The calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model wereà37.2711±3.2160,à30.1746±3.1914,à23.8953±4.4800,andà34.1350±4.3683 kcal/mol,respectively,while the calculated binding free energies wereà60.2757±4.7708,à30.9955±2.9975,à46.3099±3.5689,andà59.8104±3.5389 kcal/mol,respectively,when binding to the C-terminus.Thus,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

Genomic Evolution and Variation of SARS-CoV-2 in the Early Phase of COVID-19 Pandemic in Guangdong Province,China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)with unknown origin spread rapidly to 222 countries,areas or territories.To investigate the genomic evolution and variation in the early phase of COVID-19 pandemic in Guangdong,60 specimens of SARS-CoV-2 were used to perform whole genome sequencing,and genomics,amino acid variation and Spike protein structure modeling analyses.Phylogenetic analysis suggested that the early variation in the SARS-CoV-2 genome was still intra-species,with no evolution to other coronaviruses.There were one to seven nucleotide variations(SNVs)in each genome and all SNVs were distributed in various fragments of the genome.The Spike protein bound with human receptor,an amino acid salt bridge and a potential furin cleavage site were found in the SARS-CoV-2 using molecular modeling.Our study clarifed the characteristics of SARS-CoV-2 genomic evolution,variation and Spike protein structure in the early phase of local cases in Guangdong,which provided reference for generating prevention and control strategies and tracing the source of new outbreaks.

Research Progress on a SARS-CoV-2 Vaccine in China

Although many countries have controlled the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through strict management, there are still many countries with record-breaking numbers of new cases. Therefore, it is very important to develop a vaccine that can cause wide cross reactivity in clinical trials. At present, more than 90 vaccines are entering clinical trials and progressing smoothly, including inactivated vaccines, adenovirus-vectored vaccines and other types of vaccines. Here, we review and summarize the efficacy and potential threats of a SARS-CoV-2 vaccine. We reviewed whole-virus vaccines, adenovirus-subunit vaccines and recombinant protein vaccines and discussed the positive and negative consequences of a SARS-CoV-2 vaccine. However, there are still heated debates on the mechanism, effectiveness, and breadth of protection. In conclusion, this study can predict the risk of new coronavirus outbreaks in the future by discussing the research and development status of new coronavirus vaccines in China and other countries. Looking to the future, it is important to mine the large amount of data generated in clinical trials of universal new coronavirus vaccines to ensure that these vaccine programs are equally useful in the face of new coronavirus mutations.

基于SARS-CoV-2病毒N蛋白的抗菌肽设计及抗临床耐药菌机制研究

研究基于SARS-CoV-2病毒N蛋白的抗菌肽设计及抗临床耐药菌机制。方法 在分析SARS-CoV-2病毒N蛋白的基因序列基础上,选择形成两亲性α-螺旋的序列进行设计合成。测定肽对临床耐药菌的抗菌活性和细胞毒性,并以此为基础,通过结构测定、细胞膜渗透实验、钙黄绿素荧光探针实验和原子力显微镜实验对肽的抗菌机制进行研究。结果 临床确诊患者发病后0~1周、1~2周、2~3周、3~13周的SARS-CoV IgG和N-IgG阳性率均逐渐升高(P<0.05)。临床疑似患者发病后0~1周、2~3周的SARS-CoV IgG和N-IgG阳性率均低于发病后1~2周、3~13周(P<0.05)。临床排除患者发病后0~1周SARS-CoV IgG和N-IgG阳性率均低于发病后1~2周、2~3周、3~13周(P<0.05)。结论 研究基于SARS-CoV-2病毒N蛋白的抗菌肽设计及抗临床耐药菌机制能够将有效依据提供给临床控制与治疗细菌感染。

血清BMP-2、N-MID水平与老年股骨粗隆间骨折患者术后髋关节功能不良的关系研究

目的分析血清骨形态发生蛋白2(BMP-2)、骨钙素N端中分子片段(N-MID)水平与老年股骨粗隆间骨折患者术后髋关节功能不良的关系。方法选取2022年2月至2023年6月在该院治疗的96例老年股骨粗隆间骨折患者,根据患者术后髋关节功能的Harris评分结果分为术后良好组(n=67)和术后不良组(n=29)。收集所有患者的临床资料,检测血清BMP-2、N-MID水平并进行比较;采用多因素Spearman法分析血清BMP-2、N-MID水平与患者术后髋关节功能不良的关系;患者术后髋关节功能不良的影响因素采用多因素Logistic回归分析;血清BMP-2、N-MID水平对患者术后髋关节功能不良的预测价值用受试者工作特征(ROC)曲线进行分析。结果术后良好组与术后不良组患者的骨折Evans-Jensen分型、有无术后并发症、术后内固定方式、骨质疏松分级比较,差异有统计学意义(P<0.05);术后不良组血清BMP-2、N-MID水平显著低于术后良好组,差异有统计学意义(P<0.05);老年股骨粗隆间骨折患者血清BMP-2、N-MID水平与术后髋关节功能均呈负相关(r=-0.564、-0.638,P<0.05);骨折Evans-Jensen分型Ⅲ~Ⅴ型、有术后并发症、骨质疏松分级4~6级均是老年股骨粗隆间骨折患者术后髋关节功能不良的危险因素(P<0.05),血清BMP-2、N-MID水平升高是其保护因素(P<0.05);血清BMP-2、N-MID、两者联合预测患者术后髋关节功能不良的曲线下面积(AUC)分别为0.932、0.883、0.977,联合预测价值更高(Z_(两者联合-BMP-2)=2.220,P=0.026;Z_(两者联合-N-MID)=3.162,P=0.002)。结论老年股骨粗隆间骨折术后髋关节功能不良患者血清BMP-2、N-MID水平显著降低,与患者术后髋关节功能呈负相关,两者联合能更好地预测患者术后髋关节功能不良。

可溶性生长刺激表达基因2蛋白联合N末端B型利钠肽原对急诊经皮冠状动脉介入治疗的ST段抬高型心肌梗死患者预后的预测价值

目的:探讨可溶性生长刺激表达基因2蛋白(sST2)联合N末端B型利钠肽原(NT-proBNP)对急诊经皮冠状动脉介入治疗(PCI)的ST段抬高型心肌梗死(STEMI)患者预后的预测价值。方法:收集2020年8月至2021年2月在辽宁省人民医院首次确诊STEMI并行急诊PCI的患者206例。根据是否在随访期内发生主要不良心血管事件(MACE,包括心原性死亡、脑卒中、心力衰竭及缺血驱动的血运重建的复合终点事件)分为MACE组和非MACE组。采用Cox回归分析STEMI患者急诊PCI后发生MACE的独立危险因素,并采用ROC曲线评估sST2和NT-proBNP对STEMI患者急诊PCI后发生MACE的预测价值,并用Delong检验分析单用sST2或NT-proBNP及sST2联合NT-proBNP的预测效能。结果:随访3年,共发生MACE 62例。与非MACE组比较,MACE组患者sST2、NT-proBNP水平均较高,左前降支病变、前壁心肌梗死患者比例较高,LVEF较低,冠状动脉慢血流比例较大(P均<0.05)。多因素Cox回归分析显示,sST2(HR=1.018,95%CI:1.012~1.024,P<0.001)和NT-proBNP(HR=1.001,95%CI:1.000~1.010,P<0.001)均是MACE的独立预测因素。根据ROC曲线和Delong检验分析显示,sST2联合NT-proBNP预测MACE的AUC为0.854,灵敏度为64.5%,特异度为93.1%,sST2联合NT-proBNP预测MACE的效能优于单用sST2或NT-proBNP(Z=2.119,P=0.034;Z=2.178,P=0.029)。结论:sST2、NT-proBNP是预测STEMI患者急诊PCI后发生MACE的有效指标,且二者联合预测效能更佳。

Insights into the virologic and immunologic features of SARS-COV-2

The host immunity is crucial in determining the clinical course and prognosis of coronavirus disease 2019,where some systemic and severe manifestations are associated with excessive or suboptimal responses.Several antigenic epitopes in spike,nucleocapsid and membrane proteins of severe acute respiratory syndrome coronavirus 2 are targeted by the immune system,and a robust response with innate and adaptive components develops in infected individuals.High titer neutralizing antibodies and a balanced T cell response appears to constitute the optimal immune response to severe acute respiratory syndrome coronavirus 2,where innate and mucosal defenses also contribute significantly.Following exposure,immunological memory seems to develop and be maintained for substantial periods.Here,we provide an overview of the main aspects in antiviral immunity involving innate and adaptive responses with insights into virus structure,individual variations pertaining to disease severity as well as long-term protective immunity expected to be attained by vaccination.

New and Newer Vaccines for SARS-CoV-2 Variants. Are the Major Vaccine Developers on the Right Track, Or Is Delipidation the Answer?

Background: Global Covid-19 pandemic has led to remarkable scientific achievements resulting in the development and rapid implementation of vaccines towards the original wild-type SARS-CoV-2 virus. Most Covid-19 vaccines are targeted to only one protein (the Spike protein) on the virus. SARS-CoV-2 that causes Covid-19 naturally undergoes multiple mutations over time. Such mutations can be inconsequential or have dire consequences. The lack of effectiveness of current vaccines towards mutated variants of Covid-19 is of major concern. The objective of this study is to describe an optimal solvent system that creates, via delipidation, a non-synthetic, host-derived or nonhost-derived modified viral particle that has its lipid envelope removed, exposing hidden undenatured proteins from within the virus, that generate a positive immunologic response when administered into a host, thereby providing a vaccine that offers strong and broad protection against the virus. Methods: Lipid removal from viruses by specific procedures renders the exposure of hidden proteins. Protection by antibodies to all of the virus’ protein types has shown to be far superior to protection by antibodies that are created by a single protein type. Results: Published studies with the Hepatitis virus, Pestivirus and HIV virus have reported the wide range of applications with this delipidation approach resulting in effectively long-term and broad protection vaccines. Conclusion: Mutations are rendering existing vaccines less effective. New approaches to obtain a more permanent vaccine that minimizes the effects of mutation are obtainable by delipidation of the viral particle and thereby creating vaccines that are more permanent with broad protection.

Can a radioimmunoassay kit be developed for accurate detection of the S protein of severe acute respiratory syndrome coronavirus 2?

The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the end of 2019 spread worldwide within only a few months.The screening and timely isolation of infected individuals have been regarded as an effective means of epidemic prevention and control.Therefore,effective screening of infected individuals plays a vital role in epidemic prevention and control.At present,reverse transcription-polymerase chain reaction(RT–PCR)is the main method for the in vitro detection of SARS-CoV-2.However,RT–PCR requires certified laboratories,expensive equipment,and trained technicians.Therefore,it is necessary to develop simpler and more convenient methods.Some studies have shown that the PepKAA peptide has a high affinity for the S protein of SARS-CoV-2.The tyrosine in PepKAA is labeled with 125I and used to design a radioimmunoassay kit for the detection of the S protein of SARS-CoV-2,which is of great significance for the early diagnosis of COVID-19.

Comparison between SARS-CoV-2 positive and negative pneumonia in children:A retrospective analysis at the beginning of the pandemic

BACKGROUND Even though coronavirus 2019 disease(COVID-19)clinical course in children is much milder than in adults,pneumonia can occur in the pediatric population as well.Here,we reported a single-center pediatric case series of COVID-19 from Kazakhstan during the first wave of pandemic.AIM To analyze the main clinical and laboratory aspects in severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)positive and negative children diagnosed with pneumonia.METHODS This is a retrospective analysis of 54 children,who were medically assessed as close contacts of COVID-19 adults in their family setting,between June and September 2020.These children were all hospitalized:We compared the clinical and laboratory characteristics of children affected with pneumonia in the presence(group 1)or absence(group 2)of SARS-CoV-2 infection.RESULTS Overall,the main clinical manifestations at the admission were fever,cough,loss of appetite,fatigue/weakness,nasal congestion and/or rhinorrhea,and dyspnea.Based on the SARS-CoV-2 polymerase chain reaction(PCR)test,24 positive children with pneumonia(group 1)and 20 negative children with pneumonia(group 2)were identified;10 positive children did not show any radiological findings of pneumonia.No significant differences were found between the two pneumonia study groups for any clinical and laboratory parameters,except for C-reactive protein(CRP).Of course,both pneumonia groups showed increased CRP values;however,the COVID-19 pneumonia group 1 showed a significantly higher increase of CRP compared to group 2.CONCLUSION In our case series of children assessed for SARS-CoV-2 infection based on contact tracing,the acute inflammatory response and,in detail,CRP increase resulted to be more pronounced in COVID-19 children with pneumonia than in children with SARS-CoV-2-unrelated pneumonia.However,because of multiple limitations of this study,larger,controlled and more complete clinical studies are needed to verify this finding.

Ndrg2基因及NDRG2蛋白的生物信息学分析

目的 :对ndrg2 (n mycdownsreamregulatorgene 2 )基因调控区和NDRG2蛋白序列进行生物信息学分析 ,从结构上预测其功能 .方法 :运用internet网络上的数据库及程序 ,对ndrg2基因的调控区和NDRG2蛋白的二级结构进行生物信息学分析 .结果 :ndrg2基因调控区存在多种转录因子结合位点 ,功能主要涉及组织特异性表达调控 ,细胞生长发育相关基因和应激反应基因的表达调控等 ;NDRG2蛋白的结构属于α/β水解酶类折叠 ,其分类预测表明与细菌环氧化物水解酶的二级结构极为相似 .结论 :生物信息学分析提示NDRG2蛋白具有一定的酶活性 ,可能参与细胞抗氧化应激反应 ,内外源有毒物质的代谢 。

血浆sST2、cTnI、hs- CRP、NT- proBNP水平对急性心肌梗死患者不良心血管事件的评估价值

目的:初步研究血浆可溶性致癌抑制因子2(sST2)、心肌肌钙蛋白I(cTnI)、高敏-C反应蛋白(hs-CRP)和N端脑钠肽前体(NT-proBNP)在急性心肌梗死(AMI)患者主要不良心血管事件(MACE)中的评估价值。方法:前瞻性纳入我院2016年3月至2017年4月收治的128例首次发病的AMI患者为试验组,同时选择128例同期健康体检者作为对照组。采用ELISA法检测血浆中sST2、cTnI、hs-CRP、NT-proBNP水平,比较两组间的差异,并随访AMI患者出院后6个月内MACE的发生率,采用受试者工作特征曲线(ROC)计算血浆sST2、cTnI、hs-CRP、NT-proBNP水平预测患者MACE发生的曲线下面积(AUC)。结果:试验组患者血浆sST2、cTnI、hs-CRP、NT-proBNP水平显著高于对照组,差异具有统计学意义(P<0.05)。AMI患者出院后6个月内发生MACE者血浆sST2、cTnI、hs-CRP、NT-proBNP水平明显高于未发生MACE者(P<0.05)。ROC显示,血浆sST2、cTnI、hs-CRP、NT-proBNP水平均能预测患者MACE的发生,AUC分别为0.8732、0.691 6、0.817 4、0.742 5;sST2的AUC明显高于其他指标(均P<0.05),表明sST2的预测价值最高。结论:血浆sST2、cTnI、hs-CRP、NT-proBNP水平对评估AMI患者MACE的发生具有一定的临床价值,其中sST2对患者6个月MACE的发生预测价值最高。