Immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) in children aged 2–5 years in China

BackgroundThe widespread use of pneumococcal conjugate vaccines (PCVs) has significantly decreased pneumococcal disease worldwide. However, China has not adopted PCVs in their national immunization schedules and had only approved these vaccines for children aged 2–15 months by 2020.MethodsIn an open-label trial, enrolled healthy children aged 2–5 years old were randomized 1:1 and divided into a 7-valent pneumococcal conjugate vaccine (PCV7) group and a Haemophilus influenzae type b conjugate vaccine (Hib) group. Children in the PCV7 group received a single dose of PCV7, and the Hib group received a single dose of Hib vaccine. Blood samples were collected before and 6 months after vaccination. Immunogenicity and safety of PCV7 were assessed at prespecified time points.ResultsSix months after a single dose of PCV7, children in the PCV7 group for all 7 serotypes, IgG mean concentrations (GMCs) and opsonophagocytic geometric mean titres (GMTs) were significantly higher (P < .001) than at baseline, and the proportion of IgG ≥ 0.35 µg/mL ranged from 90.0% to 100%. Although the antibody level increased with age, preexisting antibodies did not induce hyporesponsiveness to PCV7. In the Hib group, the antibody levels were not significantly different or had changed slightly at 6 months. PCV7 was well tolerated in all age groups, and no serious adverse events (AEs) emerged during this study.ConclusionsA single dose of PCV7 was immunogenic and safe for Chinese children aged 2–5 years, and the preexisting antibodies against the PCV7 serotypes did not change the response to vaccination. The findings supported the effectiveness of PCV7 in this age group. PCVs with broader serotype coverage are expected to expand pneumococcal disease protection.     

Trends in maternal mortality in the United States

Maternal mortality is a major global concern. Although a notable decline in maternal mortality in the United States occurred during the mid-20th century, this progress stalled during the late 20th century. Furthermore, maternal mortality rates have increased during the early 21st century. Around the year 2000 the maternal mortality rate began to rise and has since nearly doubled. Given that at least half of maternal deaths in the U.S. are preventable, the rise in maternal deaths in the U.S. is historic and worrisome. This overview will try to provide a context for understanding the problem of this rise in maternal mortality in the U.S. by briefly discussing how maternal mortality rates are reported from National Vital Statistics data and from a National Surveillance system. Trends and causes of maternal deaths and the difficulty with interpreting these trends will be discussed.     

全面二孩政策背景下安徽省中小城市30岁及以上二孩孕妇的生育意愿与心理健康状况研究

背景　随着全面二孩政策实施，育龄妇女生育意愿受到全社会的关注，但对于超过最佳生育年龄的孕妇的生育意愿和心理健康状况的影响因素的研究却鲜见报道。目的　了解安徽省中小城市30岁及以上二孩孕妇的生育意愿和心理健康状况，为二孩政策的实施及配套政策的完善提供参考。方法　2018年4-8月采用多阶段整群抽样法，随机选取安徽省中小城市中的铜陵市、淮南市、六安市作为研究地点，选择在妇幼保健院建立妊娠期保健卡的30岁及以上的二孩孕妇作为研究对象。收集其一般人口学资料、生育意愿及生育相关特征、总体幸福感量表（GWBS）评分。采用多因素Logistic回归模型分析生育意愿、心理健康状况的影响因素。结果　共发放问卷647份，回收有效问卷618份，有效回收率为95.5%。不同年龄、身体健康状况、理想生育子女数目、周围人群生育情况、生育决定权、二孩性别期待的孕妇生育意愿比较，差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，年龄、周围人群生育状况、生育决定权、二孩性别期待是孕妇生育意愿的影响因素（P<0.05）。不愿意生育孕妇的精力、对生活的满足和兴趣、忧郁或愉快的心境、对情感和行为的控制、松弛与紧张得分、GWBS总分低于愿意生育的孕妇（P<0.05）。不同GWBS评分孕妇身体健康状况、生育意愿、生育决定权和生育政策知晓情况比较，差异均有统计学意义（P<0.05）。多因素Logistic回归分析结果显示，身体健康状况、生育意愿、生育决定权是GWBS评分的影响因素（P<0.05）。结论　安徽省中小城市30岁及以上二孩孕妇总体生育意愿较强，孕妇心理健康状况主要受生育意愿影响。相关部门应采取综合性措施，以应对政策变化带来的挑战。     

Retrievable inferior vena cava filter for primary prophylaxis of pulmonary embolism in at-risk trauma patients: A feasibility trial

ObjectiveTo determine if insertion of rIVCF for PE prophylaxis in high risk trauma patients could result in a clinically meaningful reduction (>24 h) in time that patients are left unprotected from PEsSummary and background dataTrauma patients are at high risk for the development of pulmonary embolism (PE). Early pharmacologic PE prophylaxis is ideal, however many patients are unable to receive prophylaxis due to concomitant injuries. Current guidelines are conflicting on the role of prophylactic retrievable inferior vena cava filters (rIVCF) for PE prevention in this patient population, and robust data to guide clinicians is lacking.MethodsIn this single center, randomized control trial of adult (age > 18 years) trauma patients at high risk for PE by EAST criteria and unable to receive pharmacologic prophylaxis for at least 72 h, we randomized 42 patients to receive a rIVCF or to not have a rIVCF placed. Our primary endpoints were time left unprotected to PE development and feasibility.ResultsThe median patient age was 53 years, with a median Injury Severity Score of 33. Randomization to rIVCF reduced the time left unprotected to PE (Control: 78.2 h [53.6–104]; rIVCF: 25.5 h [9.8–44.6], p = 0.0001). Two pulmonary embolisms occurred in the control group, and one in the rIVCF group. Seven deaths occurred in the control group, and 8 in the rIVCF group.ConclusionThis feasibility study demonstrates a clinically meaningful reduction in time left unprotected to PE. Further investigations powered to demonstrate a reduction in PE incidence are required.Level of evidenceLevel 1 Evidence randomized controlled trial     

Alteration of tumor suppressor BMP5 in sporadic colorectal cancer: a genomic and transcriptomic profiling based study

Background

Although the genetic spectrum of human colorectal cancer (CRC) is mainly characterized by APC, KRAS and TP53 mutations, driver genes in tumor initiation have not been conclusively demonstrated. In this study, we aimed to identify novel markers for CRC.

Methods

We performed exome analysis of sporadic colorectal cancer (sCRC) coding regions to screen loss of function (LoF) mutation genes, and carried out systems-level approaches to confirm top rank gene in this study.

Results

We identified loss of BMP5 is an early event in CRC. Deep sequencing identified BMP5 was mutated in 7.7% (8/104) of sCRC samples, with 37.5% truncating mutation frequency. Notably, BMP5 negative expression and its prognostic value is uniquely significant in sCRC but not in other tumor types. Furthermore, BMP5 expression was positively correlated with E-cadherin in CRC patients and its dysregulation play a vital role in epithelial-mesenchymal transition (EMT), thus triggering tumor initiation and development. RNA sequencing identified, independent of BMP/Smads pathway, BMP5 signaled though Jak-Stat pathways to inhibit the activation of oncogene EPSTI1.

Conclusions

Our result support a novel concept that the importance of BMP5 in sCRC. The tumor suppressor role of BMP5 highlights its crucial role in CRC initiation and development.

     

番茄红素与姜黄素联用对急性乙醇氧化损伤小鼠的抗氧化作用

目的 评价番茄红素与姜黄素联用对急性乙醇氧化损伤小鼠的抗氧化作用。方法 将50只雄性SPF级昆明种小鼠根据体质量分为5组,分别为空白对照组、模型对照组及低、中、高3个受试物剂量组(100、 200、600 mg/kg),经口灌胃给予受试物,实验持续30 d,末次灌胃后模型对照组和3个剂量组实验动物隔夜禁食16 h,按照12 mL/kg经口一次性给予50%(体积分数)乙醇致急性氧化损伤模型;空白对照组不作处理、不禁食取材;6 h后从内眦采血,测小鼠红细胞总超氧化物歧化酶(total superoxide dismutase,T-SOD)活性、全血蛋白质羰基(protein carbonyl,PC)浓度、还原型谷胱甘肽(reduced glutathione,GSH)浓度、谷胱甘肽过氧化物酶(glutathione peroxidase activities, GSH-Px)活力、丙二醛(malondialdehyde,MDA)浓度。结果 受试物高剂量组小鼠红细胞SOD活力、小鼠血液GSH-Px活力和GSH浓度均高于模型对照组(P<0.05),且高剂量组小鼠全血PC浓度低于模型对照组(P<0.05)。结论 番茄红素及姜黄素联用具有抗氧化功能,能够改善急性乙醇氧化损伤小鼠的氧化损伤。     

Multiregion whole-exome sequencing of matched primary and metastatic tumors revealed genomic heterogeneity and suggested polyclonal seeding in colorectal cancer metastasis

BackgroundDistant metastasis accounts for 90% of deaths from colorectal cancer (CRC). Genomic heterogeneity has been reported in various solid malignancies, but remains largely under-explored in metastatic CRC tumors, especially in primary to metastatic tumor evolution.Patients and methodsWe conducted high-depth whole-exome sequencing in multiple regions of matched primary and metastatic CRC tumors. Using a total of 28 tumor, normal, and lymph node tissues, we analyzed inter- and intra-individual heterogeneity, inferred the tumor subclonal architectures, and depicted the subclonal evolutionary routes from primary to metastatic tumors.ResultsCRC has significant inter-individual but relatively limited intra-individual heterogeneity. Genomic landscapes were more similar within primary, metastatic, or lymph node tumors than across these types. Metastatic tumors exhibited less intratumor heterogeneity than primary tumors, indicating that single-region sequencing may be adequate to identify important metastasis mutations to guide treatment. Remarkably, all metastatic tumors inherited multiple genetically distinct subclones from primary tumors, supporting a possible polyclonal seeding mechanism for metastasis. Analysis of one patient with the trio samples of primary, metastatic, and lymph node tumors supported a mechanism of synchronous parallel dissemination from the primary to metastatic tumors that was not mediated through lymph nodes.ConclusionsIn CRC, metastatic tumors have different but less heterogeneous genomic landscapes than primary tumors. It is possible that CRC metastasis is, at least partly, mediated through a polyclonal seeding mechanism. These findings demonstrated the rationale and feasibility for identifying and targeting primary tumor-derived metastasis-potent subclones for the prediction, prevention, and treatment of CRC metastasis.     

纳米二氧化硅颗粒对血管内皮细胞的毒性及其凋亡诱导作用

目的:研究纳米二氧化硅(SiO₂)颗粒的血管内皮细胞毒性和可能的作用机制,为探讨纳米SiO₂颗粒毒性效应及安全性评价提供参考依据。方法:将体外培养的人脐静脉内皮细胞(HUVECs)随机分为对照组和不同浓度纳米SiO₂颗粒暴露组,暴露浓度分别为12.5、25.0、50.0及100.0 mg·L^-1。采用透射电镜(TEM)观察纳米SiO₂颗粒粒径、形貌及分散性。细胞处理24 h后,电感耦合等离子体原子发射光谱(ICP-AES)法测定细胞中硅水平;MTT法测定细胞活力;乳酸脱氢酶(LDH)释放法检测细胞膜的完整性;DCFH-DA荧光探针标记激光共聚焦显微镜观察细胞中活性氧(ROS)水平;DAPI染色荧光显微镜下观察细胞核形态;Annexin Ⅴ/PI双染标记流式细胞术(FCM)检测细胞凋亡率;罗丹明123线粒体试剂盒检测细胞线粒体膜电位。结果:TEM观察,纳米SiO₂颗粒分布均匀,大小一致,颗粒呈球形,分散性好,未发生聚集。用Image J 软件计算得到颗粒平均粒径为(57.66 ± 7.30)nm。与对照组比较,纳米SiO₂颗粒作用于HUVECs后,细胞活力下降(P<0.05),细胞中硅水平和培养液中LDH活性增加(P<0.05),细胞中ROS水平升高,线粒体膜电位下降,甚至发生细胞凋亡。上述细胞效应均表现为随颗粒作用浓度的增加而逐渐明显,呈现一定的剂量依赖关系。结论:纳米SiO₂颗粒具有血管内皮细胞毒性,可诱导ROS生成和氧化应激,从而破坏细胞膜、损伤线粒体,最终引发细胞凋亡。     

Variation in ‘standard care’ for breast cancer across Europe: A EUROCARE-3 high resolution study

On a population-based sample of 13,500 European breast cancer patients mostly diagnosed in 1996–1998 and archived by 26 cancer registries, we used logistic regression to estimate odds of conservative surgery plus radiotherapy (BCS + RT) versus other surgery, in T1N0M0 cases by country, adjusted for age and tumour size. We also examined: BCS + RT in relation to total national expenditure on health (TNEH); chemotherapy use in N+ patients; tamoxifen use in oestrogen-positive patients; and whether ?10 nodes were examined in lymphadenectomies. Stage, diagnostic examinations and treatments were obtained from clinical records.T1N0M0 cases were 33.0% of the total. 55.0% of T1N0M0 received BCS + RT, range 9.0% (Estonia) to 78.0% (France). Compared to France, odds of BCS + RT were lower in all other countries, even after adjusting for covariates. Women of 70–99 years had 67% lower odds of BCS + RT than women of 15–39 years. BCS + RT was 20% in low TNEH, 58% in medium TNEH, and 64% in high TNEH countries. Chemotherapy was given to 63.0% of N+ and 90.7% of premenopausal N+ (15–49 years), with marked variation by country, mainly in post-menopause (50–99 years). Hormonal therapy was given to 55.5% of oestrogen-positive cases, 44.6% at 15–49 years and 58.8% at 50–99 years; with marked variation across countries especially in premenopause.The variation in breast cancer care across Europe prior to the development of European guidelines was striking; older women received BCS + RT much less than younger women; and adherence to ‘standard care’ varied even among countries with medium/high TNEH, suggesting sub-optimal resource allocation.