血清生长分化因子15水平与慢性淋巴细胞白血病发生风险的关联研究

目的 采用两样本孟德尔随机化研究方法探讨血清生长分化因子15(GDF15)水平与慢性淋巴细胞白血病(CLL)发生之间的关联。方法 基于欧洲人群血清GDF15和CLL的全基因组关联研究公开数据库,筛选与血清GDF15水平相关的遗传变异位点作为工具变量,采用逆方差加权法评估遗传学预测的血清GDF15浓度与CLL发生的关联,采用最大似然比法进行敏感性分析,采用MR-Egger回归探讨工具变量潜在多效性。结果 研究共纳入3个单核苷酸多态位点作为工具变量,逆方差加权法结果显示,血清GDF15水平与CLL发生风险之间存在负相关,GDF15浓度每升高一个标准差(SD),CLL发生风险降低33%(95%置信区间:2%～54%)(P=0.039)。敏感性分析得到了一致的结果。此外,MR-Egger回归未发现存在多效性。结论 本研究结果提示,在欧洲人群中,血清GDF15水平与CLL发生之间可能存在负相关,仍需大样本人群研究及体内外实验进一步阐明GDF15在CLL发生发展中的作用及其潜在生物学机制。     

Intermittent fasting increases growth differentiation factor 15 in females with overweight or obesity but not associated with food intake

Growth differentiation factor 15 (GDF15) increases with acute fast in animals, and high GDF15 reduces food intake in rodents. We explored whether GDF15 was altered following intermittent fasting (IF) versus caloric restriction (CR), and associations with energy intake. Females with obesity received all foods at 70% (IF70 and CR70) or 100% of energy requirements for 8 weeks. IF ate 2–9% less than provided on refeeding days, resulting in greater weight losses. GDF15 was increased 5% more in IF70 versus CR70, but not associated with energy intake. This rise in GDF15 is unlikely to explain restriction of energy intake during IF.     

新型冠状病毒感染影响因素系统评价研究

目的 通过meta分析探讨感染新型冠状病毒的影响因素。方法 检索CNKI、Medline、PubMed等9个中英文数据库。独立筛选符合排纳标准的文献进行质量评价与资料提取,采用RevMan 5.4进行meta分析。结果 各影响因素的OR/MD值及95%CI分别为:人口基本特征中,年龄 4.39（1.70～7.09）、职业（医务）1.29（1.00～1.65）、种族（黑种人）2.42（1.56～3.75）、BMI1.16（1.11～1.22）;基础疾病史中,心血管疾病1.78（1.30～2.44）、糖尿病1.62（1.37～1.91）、肾脏疾病2.53（1.76～3.63）、肥胖1.45（1.12～1.87）、免疫系统疾病0.58（0.40～0.83）、痴呆4.38（2.43～7.88）、脑血管疾病1.34（1.13～1.59）;使用ACE抑制剂1.12（1.06～1.18）、胰岛素1.61（1.06～2.45）。结论 感染新型冠状病毒的危险因素多样,且根据亚组分析结果推测可能受经济水平影响,提示不同经济水平区域应针对性保护易感人群,优化卫生资源配置。     

生长分化因子15在妊娠期疾病中的作用

妊娠期疾病是妊娠过程中母体及胎儿生理机能异常出现的一系列相关疾病,严重危害母婴健康。近年研究表明生长分化因子15（GDF15）在胎盘组织特异性高表达,对于维持妊娠、促进胎儿正常发育非常重要;其在妊娠剧吐、流产、妊娠期贫血、妊娠期糖尿病和妊娠期高血压疾病等多种妊娠期疾病中异常表达。GDF15作为多功能的细胞因子,可能通过调控胰岛素抵抗和葡萄糖耐受参与妊娠期能量代谢调节,同时通过调控巨噬细胞、树突状细胞等免疫细胞功能在妊娠期的免疫平衡调控方面发挥重要作用。综述GDF15在妊娠期疾病发生、发展中的作用。     

河南省境外输入新型冠状病毒感染病例流行病学特征分析

目的 分析河南省境外输入新型冠状病毒感染(简称新冠感染)病例的流行病学特征,指导疫情防控。方法 将河南省境外输入新冠感染病例作为研究对象,收集其流行病学、实验室检测等信息,采用描述流行病学方法进行分析。结果 截至2022年3月14日,河南省共报告新冠感染境外输入感染者752例,入境人员罹患率为1.20%。确诊病例196例(26.06%),无症状感染者556例(73.94%);轻型105例,占确诊病例的53.57%,普通型91例,占确诊病例的46.43%,无重型和死亡病例;初筛阳性ORF1ab基因Ct值M(P₂₅,P₇₅)为34.15(24.08,37.09),N基因Ct值M(P₂₅,P₇₅)为34.19(24.04,36.75);入境到首次检出阳性时间间隔M(P₂₅,P₇₅)为0(0,2)d,入境超14 d首次检测阳性的共20例(2.93%),其中18例入境解除隔离后存在跨省活动;境外输入病例复阳率为1.99%,复阳病例未造成二代病例;2022年境外输入疫...     

生长分化因子9、骨形态发生蛋白15信号转导机制研究进展

近年研究发现,卵母细胞来源的生长分化因子9(GDF-9)、骨形态发生蛋白15(BMP-15)是卵泡生长发育和卵巢功能的重要调节因子。两者通过自分泌和旁分泌机制,调节卵巢局部细胞的分化、增殖及其功能,调控优势卵泡的形成以及卵母细胞的成熟。GDF-9和BMP-15的下游信号通路及其调节机制亦成为近年研究的热点。着重就其基因、蛋白特点、信号转导及其调节机制作简要综述。     

GDF-15、PLA2R及CysC在2型糖尿病肾病早期诊断中的价值

目的探讨生长分化因子-15(GDF-15)、M型磷脂酶A2受体(PLA2R)及血清膀胱抑素C(Cys C)在2型糖尿病肾病早期诊断中的价值。方法选取于我院2013年12月—2016年3月就诊的2型糖尿病患者120例,根据其24 h尿微量白蛋白(m Alb)水平分为正常白蛋白尿组(A组)、微量白蛋白尿组(B组)及大量白蛋白尿组(C组),每组患者均为40例。分别对三组患者GDF-15、PLA2R及Cys C水平进行检测,探讨临床2型糖尿病肾病早期诊断中的应用价值。结果 A组患者GDF-15、PLA2R及Cys C指标水平依次低于B组、C组,存在显著差异(P0.05);三组患者GDF-15、PLA2R和Cys C指标水平组间对比差异显著(P0.05);经ROC曲线分析,临床早期诊断2型糖尿病肾病中GDF-15、PLA2R和Cys C指标均存在应用价值。结论 GDF-15、PLA2R及Cysc指标可作为临床早期诊断2型糖尿病肾病的辅助指标,具有一定临床推广价值。     

系统性红斑狼疮患者合并COVID-19后发生肺炎的危险因素

目的 探讨系统性红斑狼疮(SLE)患者感染新型冠状病毒(SARS-CoV-2)后发生肺炎的危险因素。方法 纳入2022年12月—2023年2月于南昌大学第一附属医院风湿免疫科就诊且完善胸部CT检查并确诊为新型冠状病毒感染(COVID-19)的250例SLE患者。根据患者胸部CT结果分为对照组和肺炎组两组。收集两组患者的人口学数据、临床资料及实验室指标,并评估患者完善胸部CT检查之前的实验室资料。通过计算受试者工作特征(ROC)曲线,确定年龄、C反应蛋白/淋巴细胞(CLR)和系统性免疫炎症指数/清蛋白(SII/ALB)对SLE患者合并COVID-19后是否发生肺炎的诊断能力。结果 250例SLE合并COVID-19患者中,188例未发生肺炎(占75.2%),为对照组;62例发生肺炎(占24.8%),为肺炎组。两组在年龄、是否接种新冠疫苗、是否合并肾功能不全、是否合并心血管疾病、是否合并糖尿病、中性粒细胞/淋巴细胞(NLR)、血小板/淋巴细胞(PLR)、淋巴细胞/单核细胞(LMR)、系统性免疫炎症指数(SII)、SII/ALB和CLR等方面比较,差异有统计学意义(均P<0.05)。在...     

Intramuscular administration of recombinant Newcastle disease virus expressing SARS-CoV-2 spike protein protects hACE-2 TG mice against SARS-CoV-2 infection

Coronavirus disease 2019 (Covid-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) became a pandemic, causing significant burden on public health worldwide. Although the timely development and production of mRNA and adenoviral vector vaccines against SARS-CoV-2 have been successful, issues still exist in vaccine platforms for wide use and production. With the potential for proliferative capability and heat stability, the Newcastle disease virus (NDV)-vectored vaccine is a highly economical and conceivable candidate for treating emerging diseases. In this study, a recombinant NDV-vectored vaccine expressing the spike (S) protein of SARS-CoV-2, rK148/beta-S, was developed and evaluated for its efficacy against SARS-CoV-2 in K18-hACE-2 transgenic mice. Intramuscular vaccination with low dose (10^6.0 EID₅₀) conferred a survival rate of 76 % after lethal challenge of a SARS-CoV-2 beta (B.1.351) variant. When administered with a high dose (10^7.0 EID₅₀), vaccinated mice exhibited 100 % survival rate and reduced lung viral load against both beta and delta variants (B.1.617.2). Together with the protective immunity, rK148/beta-S is an accessible and cost-effective SARS-CoV-2 vaccine.     

新型冠状病毒感染不同阶段的传染性研究进展

新型冠状病毒（新冠病毒）感染不同阶段的传染性特征是调查病例感染来源、确定密切接触者范围和病例隔离时间等防控措施的重要基础。本文通过对国内外文献、技术报告与专业指南等资料进行综述,基于病原学和流行病学两个维度的研究结果,探讨新冠病毒感染者在潜伏期、临床症状期和恢复期阶段的传染性特征。现有研究提示,新冠病毒感染者在潜伏期末...     

全球SARS-CoV-2再次感染率的Meta分析

目的  系统评估SARS-CoV-2再次感染率,为减少SARS-CoV-2再次感染的发生提供循证依据。方法  检索PubMed、Embase、Web of Science、中国知网和万方等电子数据库自建库至2022年12月11日与SARS-CoV-2再次感染相关的队列研究或病例对照研究,按照严格的纳入排除标准筛选文献、提取数据并进行质量评价,采用Stata 16.0统计软件进行统计分析。结果  共纳入24篇文献,包含初次感染患者6 616 869例、再次感染者78 635例。初次感染者的再次感染率为2.06%(95% CI: 1.73%~2.40%)。相比于其他年龄组,40岁以上中年人的再次感染率更高,40~＜50岁人群为2.97%(95% CI: -1.20%~7.14%),50~＜60岁人群为2.32%(95% CI: -0.74%~5.38%)。相比于接种新型冠状病毒疫苗(简称新冠疫苗)人群,未完全接种组的再次感染率为1.85%(95% CI: 1.63%~2.08%),完全接种组的再次感染率为1.11%(95% CI: 0.34%~1.89%),未接种疫苗人群的再次感染率更高为5.47%(95% CI: 1.99%~8.95%)。医护人员的再次感染率为6.02%(95% CI: 5.67%~6.37%)。结论  SARS-CoV-2存在再次感染的风险,但本研究结果表明再次感染的比例不高。建议科学认识SARS-CoV-2的再次感染风险,加强公众健康宣教,保持健康习惯,减少再次感染风险。     

体液microRNA作为新的无创伤性生物标志物的意义

microRNA(miRNA)是一类能降解靶mRNA或抑制靶mRNA翻译从而在转录后水平调控基因表达的非编码RNA。miRNA在多种生理、病理过程中发挥重要作用,组织细胞miRNA表达谱与多种病理尤其是肿瘤密切相关。最近的研究发现,血循环及其他体液中也存在丰富而稳定的miRNA,并且在某些疾病状态下,体液中的一些miRNA表达量会发生特异性改变,提示体液miRNA作为一种新的无创伤性生物标志物的潜力和良好的临床应用前景。本文就体液miRNA与疾病关系的研究进展作一综述。     

New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates

The threat of the current coronavirus disease pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is accelerating the development of potential vaccines. Candidate vaccines have been generated using existing technologies that have been applied for developing vaccines against other infectious diseases. Two new types of platforms, mRNA- and viral vector-based vaccines, have been gaining attention owing to the rapid advancement in their methodologies. In clinical trials, setting appropriate immunological endpoints plays a key role in evaluating the efficacy and safety of candidate vaccines. Updated information about immunological features from individuals who have or have not been exposed to SARS-CoV-2 continues to guide effective vaccine development strategies. This review highlights key strategies for generating candidate SARS-CoV-2 vaccines and considerations for vaccine development and clinical trials.     

海南省不同职业人群新型冠状病毒疫苗接种情况与影响因素调查

目的 调查海南省不同职业人群新型冠状病毒疫苗(简称新冠疫苗)接种情况及其影响因素。方法 2021年5月采用分层多阶段整群随机抽样的方法，抽取240家企业和40家卫生系统单位进行问卷调查。对调查结果的单因素分析采用χ²分析，多因素分析采用logistic回归分析。结果 在7 217名调查对象中，新冠疫苗已接种6 944人(96.22%)。多因素logistic回归分析显示女性(OR=0.453,95%CI:0.347～0.591)、企业(OR=0.507,95%CI:0.354～0.727)、大专(OR=0.479,95%CI:0.344～0.667)和高中中专及以下学历(OR=0.387,95%CI:0.278～0.539)的职业人群疫苗接种积极度低。接种原因中认同度最高的是接种免费且便利、政府号召和单位组织，但单位组织和接种免费且便利对不同职业人群的影响差异无统计学意义。结论 海南省不同职业人群新冠疫苗接种率较高，应针对不同类型的职业人群开展新冠疫苗相关知识宣教，进一步提高疫苗接种率。     

Delay between COVID-19 complete vaccination and SARS-CoV-2 infection among healthcare workers

ObjectivesHealthcare workers (HCWs), at increased risk of coronavirus disease 2019 (COVID-19) were among the primary targets for vaccination, which became mandatory for them on September 15th, 2021 in France. In November they were confronted to the fifth COVID-19 wave despite excellent vaccine coverage. We aimed to estimate the incidence of SARS-CoV-2 infection after complete vaccination among HCWs with different vaccination schemes, and its determinants.MethodsWe enrolled all HCWs in the university hospital of Rennes, France who had received complete vaccination (two doses of COVID-19 vaccine). The delay from last vaccination dose to SARS-CoV-2 infection was computed. Fitted mixed Cox survival model with a random effect applied to exposure risk periods to account for epidemic variation was used to estimate the determinants of SARS-CoV-2 infection after complete vaccination.ResultsOf the 6674 (82%) HCWs who received complete vaccination (36% BNT162b2, 29% mRNA-1273, and 34% mixed with ChAdOx1 nCoV-19) and were prospectively followed-up for a median of 7.0 [6.3–8.0] months, 160 (2.4%) tested positive for SARS-CoV-2 by RT-PCR. Incidence density of SARS-CoV-2 infection after complete vaccination was 3.39 [2.89–3.96] infections per 1000 person-month. Median time from vaccine completion to SARS-CoV-2 infection was 5.5 [3.2–6.6] months. Using fitted mixed Cox regression with the delay as a time-dependent variable and random effect applied to exposure risk periods, age (P < 0.001) was independently associated with the incidence of SARS-CoV-2 infection. Vaccine schemes were not associated with SARS-CoV-2 infection (P = 0.068). A period effect was significantly associated with the incidence of SARS-CoV-2 infection (P < 0.001).ConclusionsIn this real-world study, incidence of SARS-CoV-2 infection increases with time in fully vaccinated HCWs with no differences according to the vaccination scheme. The short delay between complete vaccination and incident SARS-CoV-2 infection highlights the need for sustained barrier measures even in fully vaccinated HCWs.     

Induction of Th1 and Th2 in the protection against SARS-CoV-2 through mucosal delivery of an adenovirus vaccine expressing an engineered spike protein

A series of recombinant human type 5 adenoviruses that express the full-length or membrane-truncated spike protein (S) of SARS-CoV-2 (AdCoV2-S or AdCoV2-SdTM, respectively) was tested the efficacy against SARS-CoV-2 via intranasal (i.n.) or subcutaneous (s.c.) immunization in a rodent model. Mucosal delivery of adenovirus (Ad) vaccines could induce anti-SARS-CoV-2 IgG and IgA in the serum and in the mucosal, respectively as indicated by vaginal wash (vw) and bronchoalveolar lavage fluid (BALF). Serum anti-SARS-CoV-2 IgG but not IgA in the vw and BALF was induced by AdCoV2-S s.c.. Administration of AdCoV2-S i.n. was able to induce higher anti-SARS-CoV-2 binding and neutralizing antibody levels than s.c. injection. AdCoV2-SdTM i.n. induced a lower antibody responses than AdCoV2-S i.n.. Induced anti-S antibody responses by AdCoV2-S via i.n. or s.c. were not influenced by the pre-existing serum anti-Ad antibody. Novelty, S-specific IgG1 which represented Th2-mediated humoral response was dominantly induced in Ad i.n.-immunized serum in contrast to more IgG2a which represented Th1-mediated cellular response found in Ad s.c.-immunized serum. The activation of S-specific IFN-? and IL-4 in splenic Th1 and Th2 cells, respectively, was observed in the AdCoV2-S i.n. and s.c. groups, indicating the Th1 and Th2 immunity were activated. AdCoV2-S and AdCoV2-SdTM significantly prevented body weight loss and reduced pulmonary viral loads in hamsters. A reduction in inflammation in the lungs was observed in AdCoV-S via i.n. or s.c.-immunized hamsters following a SARS-CoV-2 challenge. It correlated to Th1 cytokine but no inflammatory cytokines secretions found in AdCoV-S i.n. -immunized BALF. These results indicate that intranasal delivery of AdCoV2-S vaccines is safe and potent at preventing SARS-CoV-2 infections.     

南京市新冠感染疫情协查信息特征分析

目的 分析南京市新冠感染疫情协查信息的特征，为优化协查信息系统功能、完善疫情处置流程提供参考。方法 利用《江苏省突发急性传染病接触者追踪管理系统》查询2021年1月1日—10月31日期间与南京市相关的新冠感染疫情协查信息，下载数据并做分析。结果 2021年1月1日—10月31日期间，南京市共处理协查信息函件16 239件，其中密切接触者函件7 464件，密切接触者的密切接触者函件7 633件，一般接触者函件1 142件。函件数量逐月缓慢上升，但7、8月份呈现突破性急剧增多。函件涉及全国除港澳台之外的31个省(自治区、直辖市)。本省外市发南京协查的密接人员，当日管控率高于外省发南京协查的密接人员(80.15%vs. 48.63%,χ²=38.002,P<0.05);次日管控率、延期管控率均低于外省发南京协查的密接人员(11.76%vs. 38.70%,χ²=31.967,P<0.05;2.21%vs. 10.27%,χ²=8.488,P<0.05)。结论 有必要建立一套可供全国各省市区直接使用的、可实现协...     

免疫缺陷人群新型冠状病毒感染诊治策略中国专家共识(2023.V2版)

自2019年年底以来,新型冠状病毒(以下简称新冠病毒)感染席卷全球,给人类社会带来极大危害,卫生经济负担显著增加。奥密克戎变异株由于传染性更强、传播力更快、再感染率更高,现已取代德尔塔变异株成为我国境外输入和本土疫情的主要流行株。我国《新型冠状病毒感染诊疗方案(试行第十版)》中强调“强化重点人群保护”,其中就包括数量越来越多的免疫缺陷人群。此类人群罹患新冠病毒感染后重症发生率高、病死率高,属于重型/危重型高危人群;而且由于基础疾病的存在,此类人群长期服用免疫抑制剂等相关药物,抗新冠病毒的治疗药物与原有药物之间复杂的相互作用,给新冠病毒感染后的治疗带来极大挑战。目前,尚缺乏可供参考的针对免疫缺陷人群新冠病毒感染诊疗的相关指南或共识。因此,广州呼吸健康研究院、国家呼吸医学中心组织国内多学科(呼吸与危重症医学科、器官移植科、风湿免疫科、血液科、感染科、重症医学科等)专家,基于循证医学证据,经过多次讨论,总结出13条建议供同行参考,以期为该类特殊人群的诊治策略提供理论和实践参考。