卵巢癌转移体细胞突变及其相关功能通路分析

目的 借助癌症体细胞突变目录（COSMIC）数据库中原发性卵巢癌和转移性卵巢癌两类癌组织的全外显子测序数据,筛选转移性癌相对于原发性癌突变率差异具有统计学意义的体细胞基因群,并对其影响的功能和信号通路进行分析。方法 从COSMIC数据库下载全部肿瘤的全外显子测序数据,从中提取全部卵巢癌全外显子测序数据,在R 3.5.3环境下,对每个基因突变在原发性卵巢癌和转移性卵巢癌两类样本中的突变率行χ²检验或Fisher确切概率法分析,寻找突变率差异具有统计学意义的基因群,并进一步将差异突变基因群进行基因本体（GO）功能及京都基因与基因组百科全书（KEGG）通路富集分析,探寻其显著富集的GO功能和KEGG通路。结果 对比原发性卵巢癌与转移性卵巢癌两类组织样本共发现520个突变率差异具有统计学意义的体细胞突变基因,包括跨膜丝氨酸蛋白酶13（TMPRSS13）、高尔基蛋白转运抑制剂A抗性因子1（GBF1）、Fos样抗体2（FOSL2）、主导控制样蛋白3（MAML3）等。突变基因群GO功能富集分析发现显著富集的GO功能包括突触前组织、树突发育、通过质膜黏附分子的细胞黏附、肌动蛋白结合等,突变基因群KEGG通路富集分析发现显著富集通路包括肌动蛋白细胞骨架的调节、三磷酸腺苷结合盒运载体等。结论 探寻原发性卵巢癌与转移性卵巢癌之间差异体细胞突变基因群及其相关功能通路可为深入揭示卵巢癌的转移调控机制提供线索,显著突变基因群可能成为卵巢癌转移诊治的生物标志物。     

迷走神经电刺激对急性呼吸窘迫综合征中Th17和Treg 蛋白变化及炎性因子的影响

目的 探讨迷走神经电刺激（Vagus nerve stimulation, VNS）调控脂多糖（LPS）诱导的急性呼吸窘迫征（acute respiratory distress syndrome, ARDS）体内Th17和Treg 蛋白变化控制炎症的机制。方法 以2mg/kg LPS 鼻管滴注SD大鼠,6h后给予左侧颈部迷走神经以10min,5V,5Hz,2ms频率刺激, 2h后取双肺及脾组织进行检测。大鼠随机分为Control组、LPS组和LPS+VNS组,每组10只。检测肺泡灌洗液总蛋白含量,测定肺部湿干比,H-E染色检测肺部炎症程度,蛋白免疫印迹法及免疫组化检测肺及脾组织Foxp3及Rorγt蛋白表达,ELISA检测肺部灌洗液中TNF-α、IL-1β、IL-6、IL-17、IL-10水平。结果 成功构建大鼠ARDS模型。与Control组相比,LPS组肺泡灌洗液总蛋白含量增高（P<0.001）,湿干比增高（P<0.001）,IL-1β、IL-6、IL-17、IL-10表达升高（均P <0.01）和TNF-α表达升高,肺和脾组织中Foxp3和Rorγt蛋白表达上升;与LPS组相比,LPS+VNS组肺泡灌洗液总蛋白含量降低（P<0.05）,湿干比下降（P<0.05）,IL-6、IL-17降低（P<0.05或P<0.01）,IL-10升高（P<0.01）,肺及脾组织中Foxp3蛋白表达上调（P<0.05）和Rorγt蛋白表达下降。结论 VNS可通过调控肺和脾组织Th17和Treg蛋白进而调控炎性因子,减轻LPS诱导的ARDS病理改变,保护组织。     

“单独二胎”政策下陕西省部分家庭生育意愿及其影响因素调查

“单独二胎”政策从提出到推行,一直是全社会的焦点,围绕这一政策合理与否,各方也提出了各种观点。通过对未达适婚年龄的独生子女、已达适婚年龄的独生子女和已达适婚年龄的非独生子女3类人群的调查,分别了解了他们对于“单独二胎”政策的认识和看法,继而从3个角度对政策的普及前景及影响因素进行统计分析。从结果看,由于政策尚在初始普及阶段,出于许多现实因素的限制和考量,符合要求的年轻夫妇生育意愿并不是很积极,若想进一步普及推行此政策,尚有许多问题需要解决。     

Attitudes Toward the Global Allocation of Chinese COVID-19 Vaccines: Cross-sectional Online Survey of Adults Living in China

BackgroundCOVID-19 vaccines are in short supply worldwide. China was among the first countries to pledge supplies of the COVID-19 vaccine as a global public product, and to date, the country has provided more than 600 million vaccines to more than 200 countries and regions with low COVID-19 vaccination rates. Understanding the public’s attitude in China toward the global distribution of COVID-19 vaccines could inform global and national decisions, policies, and debates.ObjectiveThe aim of this study was to determine the attitudes of adults living in China regarding the global allocation of COVID-19 vaccines developed in China and how these attitudes vary across provinces and by sociodemographic characteristics.MethodsWe conducted a cross-sectional online survey among adults registered with the survey company KuRunData. The survey asked participants 31 questions about their attitudes regarding the global allocation of COVID-19 vaccines developed in China. We disaggregated responses by province and sociodemographic characteristics. All analyses used survey sampling weights.ResultsA total of 10,000 participants completed the questionnaire. Participants generally favored providing COVID-19 vaccines to foreign countries before fulfilling domestic needs (75.6%, 95% CI 74.6%-76.5%). Women (3778/4921, 76.8%; odds ratio 1.18, 95% CI 1.07-1.32; P=.002) and those living in rural areas (3123/4065, 76.8%; odds ratio 1.13, 95% CI 1.01-1.27; P=.03) were especially likely to hold this opinion. Most respondents preferred providing financial support through international platforms rather than directly offering support to individual countries (72.1%, 95% CI 71%-73.1%), while for vaccine products they preferred direct provision to relevant countries instead of via a delivery platform such as COVAX (77.3%, 95% CI 76.3%-78.2%).ConclusionsAmong our survey sample, we found that adults are generally supportive of the international distribution of COVID-19 vaccines, which may encourage policy makers to support and implement the distribution of COVID-19 vaccines developed in China worldwide. Conducting similar surveys in other countries could help align policy makers’ actions on COVID-19 vaccine distribution with the preferences of their constituencies.     

脐血和新生儿外周血CD4+CD25+调节性T细胞的表型特征及意义

目的 探讨脐血和新生儿外周血中CD4 CD25 调节性T细胞的表型特征及其意义.方法以18份脐血和9份新生儿外周血为标本,细胞膜表面抗原采用单抗直接标记法,检测胞内抗原(CD152、FoxP3)时先标记膜表面抗原,固定破膜后再标记胞内抗原,应用多参数流式细胞仪进行检测和结果分析.结果脐血和新生儿外周血中的CD4 CD25 T细胞显示为独立的细胞群,脐血中该群细胞占CD4 T细胞比例为(9.26±2.43)%,新生儿外周血中的比例则为(9.35±2.30)%;在表型方面,大部分是CD45RA 的细胞,同时表达CD62L、胞浆内的CD152,也表达FoxP3,CD4 CD25 FoxP3 占CD4 T细胞比例为(1.92±0.28)%.结论 脐血和新生儿外周血中存在着一群单纯且水平较高的CD4 CD25 调节性T细胞,它们可能在发挥对母体非遗传性抗原的耐受及防止母体对胎儿的排斥反应中具有独特的作用.     

Positioning the six‐month review in the recovery process post‐stroke: The ideology of personal responsibility

Stroke is the UK's fourth highest cause of death and an estimated 300,000 people in England are living with related disability. This paper explores the six‐month review (6MR), a policy initiative that aimed to ameliorate unmet need. A multiple case study approach underpinned by critical realism was used to elicit the views of patients, carers, providers and commissioners across three sites using interviews, observations and documentation. Forty‐six patients (age range 28–91 years), 30 carers and 28 professionals were interviewed between December 2015 and October 2016. Twenty‐nine reviews were observed. Data was analysed thematically across sites. 6MRs carried out by stroke nurse specialists (SNSs) were found to be more medically orientated than those completed by a Stroke Association (SA) co‐ordinator who focused on social issues. Reviewers regarded reviews primarily as an opportunity to address unmet need and signpost to further services. Patients responded in three different ways: proactive and engaged, reflected an active orientation to recovery and self‐management; proactive and self‐managing on their own terms, encompassed patients who were striving for independence but took their own approach sometimes at odds with that of clinicians; and passive orientation, whereby patients did not engage in rehabilitation or self‐management. Patients identified different priorities to those of reviewers, particularly those with other long‐term conditions and this appeared to contribute to the dissatisfaction that some expressed. In conclusion, there was little evidence that the 6MR played a key role in recovery. Locally defined outcomes for the 6MR reflecting national policy were not substantiated by the findings. Our findings suggest that the 6MR should review therapy goals and facilitate patient‐led goals. Reviewers should be allowed the freedom to individualise the process rather than adhering to a rigid framework dictated by national policy and local protocols.     

Association between state physical education (PE) requirements and PE participation,physical activity,and body mass index change

Objective

To determine if state physical education (PE) laws are associated with student physical education attendance and physical activity (PA), and whether physical education and competitive food laws, in conjunction, are associated with lower BMI change.

Method

State laws regarding physical education time requirements and competitive foods in 2003 and 2006 were classified as strong, weak, or none, based on codified law ratings obtained from the Classification of Laws Associated with School Students. Laws were linked to student data on PE attendance and physical activity (8th grade, Spring 2007) and BMI change (5th–8th grade, 2004–2007), obtained from the Early Childhood Longitudinal Study (n = 5510 students in 40 states).

Results

Girls reported 0.31 more days of activity (95% CI: 0.02, 0.61) and were more likely to attend physical education ≥ 3 days/week (74.1% versus 52.1%, difference = 22.0, 95% CI: 2.1, 42.0) if they resided in states with strong physical education laws compared to no physical education laws. Weak physical education laws had modest associations with PE and activity, and there was no evidence that weak laws reduce BMI gain regardless of competitive food laws.

Conclusion

Strong physical education laws with specific time requirements may increase physical education attendance and activity in girls. There is insufficient evidence that physical education laws reduce student weight gain.     

Effect of the Affordable Care Act on healthcare utilization for Veterans with spinal cord injuries and disorders

Context/Objective: Provisions of the Affordable Care Act (ACA) potentially increase insurance options for Veterans with disabilities. We examined Veterans with spinal cord injuries and disorders (SCI/D) to assess whether the ACA was associated with changes in healthcare utilization from Department of Veterans Affairs (VA) healthcare facilities.Design: Using national VA data, we investigated impacts on VA healthcare utilization pre- (2012/13) and post-ACA (2014/15) implementation with negative binomial regression models.Setting: VA healthcare facilities.Participants: 8,591 VA users with SCI/D. Veterans with acute myelitis, Guillain-Barré syndrome, multiple sclerosis, or amyotrophic lateral sclerosis were excluded as were patients who died during the study period.Interventions: We assessed VA healthcare utilization before and after ACA implementation.Outcome Measures: Total numbers of VA visits for SCI/D care, diagnostic care, primary care, specialty care, and mental health care, and VA admissions.Results: The number of VA admissions was 7% higher in the post than pre-ACA implementation period (P < 0.01). The number of VA visits post-implementation increased for SCI/D care (8%; P < 0.01) and specialty care (12%; P < 0.001). Conversely, the number of mental health visits was 17% lower in the post-ACA period (P < 0.001). Veterans with SCI/D who live <5 miles from their nearest VA facility received VA care more frequently than those ≥40 miles from VA (P < 0.001).Conclusion: Counter to expectations, results suggest that Veterans with SCI/D sought more frequent VA care after ACA implementation, indicating Veterans with SCI/D continue to utilize the lifelong, comprehensive care provided at VA.     

网络安全问题初探

目的应该更加重视和关注计算机网络的安全问题。方法通过对计算机网络安全的威胁和现有的网络安全技术进行分析认识,从而得出计算机网络的安全策略。结果在对网络安全技术和安全策略的运用下,网络安全问题得到很好的改善。结论网络安全问题是个很大的系统工程,需要多方面相互协调配合,形成一个完整的安全保障体系,要达到理想的计算机网络安全还有很长的路要走。     

Opposition to voluntary and mandated COVID-19 vaccination as a dynamic process: Evidence and policy implications of changing beliefs

COVID-19 vaccination rates slowed in many countries during the second half of 2021, along with the emergence of vocal opposition, particularly to mandated vaccinations. Who are those resisting vaccination? Under what conditions do they change their minds? Our three-wave representative panel survey from Germany allows us to estimate the dynamics of vaccine opposition, providing the following answers. Without mandates, it may be difficult to reach and to sustain the near-universal level of repeated vaccinations apparently required to contain the Delta, Omicron, and likely subsequent variants. But mandates substantially increase opposition to vaccination. We find that few were opposed to voluntary vaccination in all three waves of the survey. They are just 3.3% of our panel, a number that we demonstrate is unlikely to be the result of response error. In contrast, the fraction consistently opposed to enforced vaccinations is 16.5%. Under both policies, those consistently opposed and those switching from opposition to supporting vaccination are sociodemographically virtually indistinguishable from other Germans. Thus, the mechanisms accounting for the dynamics of vaccine attitudes may apply generally across societal groups. What differentiates them from others are their beliefs about vaccination effectiveness, their trust in public institutions, and whether they perceive enforced vaccination as a restriction on their freedom. We find that changing these beliefs is both possible and necessary to increase vaccine willingness, even in the case of mandates. An inference is that well-designed policies of persuasion and enforcement will be complementary, not alternatives.

The challenge of the first half-year of most COVID-19 vaccination campaigns was the supply of vaccines, not demand for them. It then appeared that, once vaccines were widely available, vaccination rates would approach the two-thirds level initially thought to be sufficient to control the pandemic. But the Delta and then Omicron variants along with substantial and persistent reported opposition to vaccination have raised doubts about whether vaccine willingness will be sufficient. In response, by the end of 2021, vaccination mandates were being widely adopted by governments, businesses, and educational institutions, and universal mandates were being considered and implemented (1–8).The appropriate strategies for raising vaccination rates depend on the target rate, on how many are unlikely to be vaccinated willingly in a sufficiently timely manner, on the conditions under which opponents change their minds, and on the effect of the policies themselves on vaccination preferences. Our study sheds light on the behavioral side of this evaluation.