Serological response with Heplisav-B® in prior Hepatitis B vaccine non-responders living with HIV

BackgroundAs people living with HIV (PLWH) are at risk for contracting Hepatitis B Virus (HBV), they should be screened for HBV and vaccinated if not immune. Seroconversion rates in PLWH receiving traditional recombinant HBV vaccines (Engerix-B® and Recombivax-HB®) have historically been low with at most 70% achieving immunity. In 2017, a recombinant, adjuvanted HBV vaccine (Heplisav-B®) was approved for use in HIV-negative patients.Heplisav-B® has shown superior seroprotection in this population compared to Engerix-B® and Recombivax-HB®, as well as interim analysis showing higher seropositivity rates in patients undergoing dialysis. However, its efficacy in PLWH is currently unknown. This study evaluates the rate of seroconversion following Heplisav-B® administration in PLWH with previous HBV vaccination failure.MethodsRetrospective, cross-sectional study at The Brooklyn Hospital Center’s HIV primary care clinic in Brooklyn, NY. HIV-positive adults who received at least two doses of Heplisav-B® and had previously failed to seroconvert after vaccination with Engerix-B® or Recombivax-HB® were included. The primary outcome is the percentage of PLWH who became seropositive following Heplisav-B®.ResultsA total of 67 patients met the inclusion criteria. Twenty-five (37.3%) PLWH had failed at least 2 courses of recombinant vaccines. Fifty-eight (86.6%) PLWH became seropositive (Anti-HBs > 10 mIU/mL) at least two months after completing Heplisav-B®. For the 9 (13.4%) patients that did not develop immunity, 3 (33%) had a detectable HIV RNA and 3 (33%) had a CD4 count < 200 cells/uL³.ConclusionsHeplisav-B® was highly effective in achieving immunity to HBV in PLWH who failed non-adjuvanted recombinant vaccines.     

Prevention of hepatitis B mother-to-child transmission in Namibia: A cost-effectiveness analysis

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model’s outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.     

Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine – United States, 2014–2019

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.     

用体外器官培养方法研究EDCs对新生小鼠睾丸的影响

目的 通过已建立的小鼠睾丸体外培养系统,研究四种内分泌干扰物（Endocrine Disrupting Chemicals,EDCs）对男性内分泌系统的影响。 方法 将新生小鼠的睾丸组织在体外环境中培养24h,而后在培养基中分别加入浓度为0.1μM, 1μM, 10μM and 100μM的四种（DEHP、MEHP、NP、p, p’-DDE）内分泌干扰物并培养72h,同时设置对照组;培养结束后进行组织学观察,测定冻存培养基中睾酮和抑制素βB (INH-βB)的分泌水平,同时测定细胞色素P450侧链裂解酶(P450Scc)、3β-羟基类固醇脱氢酶(3β-HSD)、细胞色素P45017α-羟化酶(P450C17)和波形蛋白（vimentin）的基因表达情况。 结果 所有剂量组中睾酮的分泌水平均发生改变;P450Scc、3β-HSD、P450C17和INH-βB蛋白质的表达及mRNA水平均受到四种内分泌干扰物的影响（P<0.05）;DEHP和MEHP降低了波形蛋白的mRNA水平（P<0.05）,而NP和p, p’-DDE对波形蛋白没有显著影响（P>0.05）。 结论 本研究建立的体外培养新生小鼠睾丸模型中,所选的四种已知EDCs改变了两种睾丸激素水平,三种类固醇合成酶以及与支持细胞功能相关的波形蛋白的表达。     

云南省跨境婚姻家庭艾滋病、梅毒和乙肝检测现状分析

目的 了解云南省中-缅、中-老、中-越跨境婚姻家庭艾滋病、梅毒和乙肝检测情况,为完善跨境婚姻家庭预防母婴传播相关服务政策提供科学依据。 方法 对目前居住在云南省边境地区的中国籍和跨境婚姻家庭进行调查和访谈,收集一般人口学特征、最近一次怀孕期间三病检测情况等信息。经整理后,使用构成比和率对指标进行计算,使用卡方检验、秩和检验比较中国籍和跨境婚姻家庭各项检测服务状况。 结果 外籍媳妇主要以农民、文盲/小学、无经济收入的少数民族为主。配偶检测率,老挝籍低于当地中国籍媳妇（〖XC五号.EPS;P〗=7.87,P=0.005）,缅甸籍、越南籍与当地中国籍没有差异;缅甸籍高于老挝籍和越南籍（〖XC五号.EPS;P〗=41.84,P＜0.001）。三病检测点知晓率,缅甸籍媳妇低于当地中国籍媳妇（〖XC五号.EPS;P〗=6.11,P＜0.03）,越南籍、老挝籍与当地中国籍没有差异;老挝籍高于缅甸籍和越南籍（〖XC五号.EPS;P〗=44.03,P＜0.001）。获得预防母婴传播相关知识比例,三个外籍媳妇均低于当地中国籍（〖XC五号.EPS;P〗=19.84,P＜0.001;〖XC五号.EPS;P〗=7.52,P=0.006;〖XC五号.EPS;P〗=4.38,P=0.036）。 结论 边境地区针对跨境婚姻家庭开展艾滋病、梅毒和乙肝预防母婴传播相关工作取得实效,三病检测情况与当地中国籍基本一致,但在其他服务利用上仍存在一定差距,外籍媳妇孕早期三病检测率及其配偶检测率、相关预防母婴传播知识获取还有待提升,需要运用更加有效的服务管理模式来促进三病检测可及性的进一步提高。     

2型糖尿病患者并发轻度认知功能障碍危险因素的Meta分析

目的 系统评价2型糖尿病患者并发轻度认知功能障碍的危险因素。方法 检索CNKI、WanFang、VIP、CBM、Medline(PubMed)、EMbase、Web of Science和The Cochrane Library 数据库从建库至2020年12月2日有关2型糖尿病患者并发轻度认知功能障碍危险因素的所有文献后进行Meta分析。结果 共纳入文献18篇,研究对象3083例。各危险因素的合并OR(95%CI)为:年龄1.20(1.09,1.33)、文化程度0.67(0.55,0.82)、吸烟史1.41(0.69,2.89)、糖尿病病程1.17(1.06,1.29)、糖化血红蛋白(HbA1c)1.33(1.09,1.62)、空腹血葡萄糖(fasting blood glucose,FBG)0.88(0.75,1.03)、空腹血清C肽(Fasting c-peptide,FCP)0.41(0.16,1.04)、餐后2h血糖(2h plasma glucose,2hPG)1.90(0.52,6.87)、低密度脂蛋白胆同醇(LDL-C)1.42(1.26,1.59)、超敏C反应蛋白(high sensitive C reactive protein,hs-CRP)1.52(1.06,2.20)、胰岛素抵抗指数(HOMA-IR)1.00(0.48,2.08)、冠心病2.57(1.93,3.43)、高血压2.58(1.62,4.13)、周围神经病变1.10(0.10,12.57)。结论 高龄、文化程度低、糖尿病病程长、高HbA1c、高LDL-C、高hs-CRP、冠心病、高血压是2型糖尿病患者并发轻度认知功能障碍的主要危险因素。     

THSD7A在宫颈癌细胞侵袭、迁移等恶性生物学行为中的研究

目的 为了探索THSD7A对宫颈癌细胞的侵袭、转移以及凋亡等生物学行为的影响。方法 对宫颈癌C33a细胞和SiHa细胞培养及转染siTHSD7A基因,采用Western blotting和RT-qPCR方法在蛋白和基因水平对其验证。后应用Transwell小室实验、流式细胞术检测THSD7A沉默后对两种宫颈癌细胞的侵袭、转移、细胞周期及凋亡的改变。结果 与空白组和阴性对照组相比,沉默THSD7A的表达后,宫颈癌C33a细胞和SiHa细胞的侵袭、迁移能力明显下降（P＜0.01）;进入S期和G2/M期细胞数目减少,凋亡比例增高（P＜0.05）。结论 提示THSD7A可能作为一种致癌基因,在宫颈癌恶性生物学行为的发展过程中起到推进作用。     

The neu-protein and breast cancer

The neu-protein is overexpressed in about 20% of invasive duct cell carcinomas of the breast. The only reliable sign for neu-overexpression by immunohistochemistry is membrane staining. Its overexpression is correlated with decreased overall survival and disease free survival due to increased metastatic activity of neu-overexpressing tumour cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia, and to a lesser extent of its growth stimulating effect. From a clinical point of view, the assessment of neu-overexpression in breast cancer might become a useful tool in the future treatment of patients by chemotherapy, since patients whose tumour shows neu-overexpression benefit from higher doses of chemotherapy. The molecule plays a key role in the pathogenesis of Paget's disease of the breast. A chemotactic factor which is secreted by epidermal keratinocytes attracts the Paget cells to spread into the epidermis and acts via the neu-protein. In ductal carcinoma in situ, the combination of neu-overexpression and large cell type is highly correlated with extent of disease and therefore neu-overexpression might be a predictive marker for recurrence of disease after tumour resection.     

建立人微小病毒B19的PCR检测方法

人微小病毒Ｂ１９是微小病毒科中唯一能感染人的病毒。能够提供Ｂ１９抗原的病毒体外培养系统尚未建成，因此限制了血清学实验的开发和普及。为此作者建立起Ｂ１９病毒的ＰＣＲ检测方法。设计引物在表达外壳蛋白ＶＰ１基因区，扩增长度为４００ｂｐ。