Loss of the vitamin D receptor in human breast and prostate cancers strongly induces cell apoptosis through downregulation of Wnt/β-catenin signaling

Vitamin D co-regulates cell proliferation, differentiation and apoptosis in numerous tissues, including cancers. The known anti-proliferative and pro-apoptotic actions of the active metabolite of vitamin D, 1,25-dihydroxy-vitamin D [1,25（OH）2D] are mediated through binding to the vitamin D receptor （VDR）. Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation in vitro. Implantation of these VDR knockdown cells into the mammary fat pad （MDA-MB-231）, subcutaneously （PC3） or intra-tibially （both cell lines） in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls. These growth-retarding effects of VDR knockdown occur in the presence and absence of vitamin D and are independent of whether cells were grown in bone or soft tissues. Transcriptome analysis of VDR knockdown and non-target control cell lines demonstrated that loss of the VDR was associated with significant attenuation in the Wnt/0-catenin signaling pathway. In particular, cytoplasmic and nuclear β-catenin protein levels were reduced with a corresponding downregulation of downstream genes such as Axin2, Cyclin D1, interleukin-6 （IL-6）, and IL-8. Stabilization of 0-catenin using the GSK-3β inhibitor BIO partly reversed the growth-retarding effects of VDR knockdown. Our results indicate that the unliganded VDR possesses hitherto unknown functions to promote breast and prostate cancer growth, which appear to be operational not only within but also outside the bone environment. These novel functions contrast with the known anti-proliferative nuclear actions of the liganded VDR and may represent targets for new diagnostic and therapeutic approaches in breast and prostate cancer.

Loss of human epidermal receptor-2 in human epidermal receptor-2+breast cancer after neoadjuvant treatment:A case report

BACKGROUND Human epidermal receptor-2(HER-2)expression has been reported to be discordant between primary tumor and metastatic tissue.CASE SUMMARY We presented a case diagnosed with the HER-2+breast cancer patient who exhibited changes in the expression of HER-2 receptors on tumour samples from surgical specimens obtained after neoadjuvant treatment(NAT)compared with initial biopsy.The patient underwent a HER-2-targeted therapy consequently,in spite of HER+gene loss.After the surgery,the patient subsequently underwent endocrine therapy and radiotherapy.CONCLUSION Changes in HER-2 expression after NAT should be retested by physicians and pathologists before systemic treatment instead of avoiding further HER-2-targeted therapy,and we will perform immunohistochemical multiple-spot biopsy analyses of other important clinical issues to better define prognosis and tailor subsequent adjuvant therapy.

Assessing Human-Wildlife Conflict in the Periphery of Loango National Park in Gabon

Human-Wildlife Conflict in Gabon is a reality occurring in almost all protected areas in the country. These conflicts create real threats both for the survival of wildlife species and of human beings. This study was carried out at the periphery of Loango National Park in Gabon. This area is particular of seeing elephants wandering around villages. Respondents for the study were drawn from a wide range of stakeholders (State administrators, farmers and NGOs). Data was collected through administration of structured questionnaires and interview guide on the;socio-economic activities. Crops produced/destroyed. Animals are involved and economic loss is incurred due to conflicts. Data was analysed using SPSS version 16 and Kobo tool box. For qualitative data chi-square, descriptive statistic and linear regression model were also used. The results of the study showed that the elephants account for (60.1%) of crop destroyed followed by Ungulates (30.4%) and lastly by rodents (0.9%). The economic damage caused by the wildlife to crops valued at 72,084 USD in the zone in 2022. An urgent solution to this conflict is needed because the consequences are visible as well as the illegal repression by communities that have led to poisoning and killing of wildlife in the study area.

The Difference of the Copy Number Variation and Loss of Heterozygosity of Human Lung Large Cell Cancer Cell Line with Different Metastatic Potential

Background and Objective It has been proven that copy number gain/or loss (copy number variation CNV) in uences gene expression and result in phenotypic variation by

Modeling Human Blockers in Millimeter Wave Radio Links

In this paper, we investigate the loss caused by multiple humans blocking millimeter wave frequencies. We model human blockers as absorbing screens of infinite height with two knife-edges, We take a physical optics approach to computing the diffraction around the absorbing screens, This approach differs to the geometric optics approach described in much of the literature. The blocking model is validated by measuring the gain from multiple-human blocking configurations on an indoor link. The blocking gains predicted using Piazzi ＇ s numerical integration method （a physical optics method） agree well with measurements taken from approximately 2.7 dB to -50 dB. Thereofre, this model is suitable for real human blockers, The mean prediction error for the method is approximately -1.2 dB, and the standard deviation is approximately 5 dB.

Assessment of Seismic Indirect Losses Based on Utility Curves

In the process of quantifying optimum seismic design parameters, the losses implying the failure of the system must be assessed. Intangibles such as human lives may lie among indirect losses. In this paper, we propose a model to calculate the value of the investment that society should be willing to make for saving lives. In order to do this, we analyze both individual and social problems. However, special treatment is given to the individual problem where the value of the life of a human being is inferred by what the person should be willing to pay or willing to accept to reduce the risk of dying. Due to the use of utility curves in the calculation of this kind of intangible, we pay special attention to shape and requirement conditions of these curves. We also pay attention when personal impact and legacies or bequests are considered in utility curves. The results are shown through some applications, especially in the computation of optimum seismic design coefficients at a low seismicity site.

Quantifying Maternal Blood Loss from the Hysterotomy at Cesarean Delivery

Background: With newer protocols, such as delayed cord clamping, becoming routine practice, determining the potential maternal consequences is important. In particular, establishing normative values for blood loss from the hysterotomy would be helpful in addressing techniques to minimize total blood loss for cesarean deliveries. Objective: Blood loss from the hysterotomy during cesarean delivery has not been reported using quantitative methods. We aimed to quantify the rate of blood loss during cesarean delivery from the hysterotomy between creation and closure. Methods: This single center, prospective, case series was collected in 2018. Women with singleton pregnancies undergoing cesarean delivery at ≥37 0/7 weeks at Brigham and Women’s Hospital were included. Delayed cord clamping was performed which allowed for quantification of blood loss through gravimetric methods and descriptive statistics were performed. Results: Twenty patients were included. The mean hysterotomy closure delay for cord blood collection was 47 seconds (SD 10.2) and the mean maternal blood volume collected was 110.8 mL (SD 53.4 mL). Blood loss per minute was calculated with a median of 150 mL/minute (IQR 88.8 mL, 95% CI 109.2 - 190.4 mL). The mean post-operative hematocrit drop was 4.4%, and there were no blood transfusions. There was a single hysterotomy extension and a quantified blood loss of 413 mL per minute. Conclusion: We found a mean blood loss of 150 mL/min without hysterotomy extension. With a hysterotomy extension, the blood lost per minute was more profound. This normative data can be helpful for surgical planning with regards to delayed cord clamping or cord blood collection for banking.

Analysis of Road Traffic Accident Costs in Sudan Using the Human Capital Method

In this study, we used the Human Capital (HC) accident analysis method, to determine the road traffic accident costs in Sudan in two successive years (2010 and 2011) with slight modifications to the recommended and known framework in the way it handles currently and future accident cost components. We evaluated and compared the significance and impact of the economic loss caused by road traffic accidents in Sudan using detailed information on road traffic accident casualties, classified by severity level, vehicle type, and other key parameters such as discount rates and medical and insurance information for Sudan in its entirety. The total cost of road traffic accidents in Sudan in 2010 was estimated at US $391 million, which represents 0.57% of the Gross Domestic Product (GDP), while in 2011 the cost was calculated to reach US $413 million, representing 0.62% of GDP. Findings show that the amount of accident costs is estimated to a certain extent at less than 1% of the total GDP of the country in the two estimation years, but we believe that the evaluation process used fulfilled the eligibility criteria of HC studies and that the produced values for Sudan are valid and reliable. Unit costs for each crash severity level were also estimated in the two years such as death, disability, serious injury, slight injury, and vehicle damage. Death or fatality was equal to US $38,932 and 39,508;disability was equal to US $43,113 and US $45,165;serious injury was equal to US $6963 and US $7596;slight injury was equal to US $2570 and US $3198 and vehicle damage only was equal to US $2268 and US $2579 in the assessment years 2010 and 2011, respectively.

考虑人体与水流相互作用的溃坝洪水生命损失评估模型

溃坝洪水会给下游人民群众造成巨大的生命损失,开展溃坝洪水造成的生命损失风险定量评估对应急抢险救灾具有重要的现实意义。本文在已有生命损失贝叶斯网络HURAM1.0模型基础上,引入了人体稳定性物理模型,考虑人体与水流相互作用关系,对处于洪水中的人先进行稳定性判定,并进行溺水判定,运用蒙特卡洛模拟方法,综合了水深和水流速对生命损失的影响,建立HURAM2.0模型;并将该模型应用于唐家山堰塞坝溃坝洪水生命损失分析。结果表明:HURAM2.0模型建立了水流流速对生命损失影响的定量关系,更精确地刻画了人体在水流中的稳定性和求生能力,相比HURAM1.0模型对较强洪水强度条件下的生命损失预测结果更准确。同时,在本文建立的模型中,除水深度、洪水严重程度变化不大,其余变量的敏感性均有所上升,其中居民区住宅层数、在建筑物中庇护情况和溃坝时长等变量对模型计算结果的最大影响程度分别增加142%、95%和93%,加强了模型在低、中、高3类洪水强度下的解释性,与HURAM1.0相比在贝叶斯反演分析中更占优势。在唐家山堰塞坝溃坝风险分析中,HURAM2.0能区分出不同水流速条件下的生命损失,更符合实际情况,即开挖泄流槽前风险大、死亡率高,在现场勘测和开挖泄流槽后风险及死亡人数大大降低,建议结合预警疏散以降低生命损失风险。

结合坐标Transformer的轻量级人体姿态估计算法

针对现有的大多数自底向上人体姿态估计算法存在模型规模大、计算成本高及对边缘设备不友好等问题,提出了一种基于YOLOv5s6-Pose的轻量级多人姿态估计网络模型YOLOv5s6-Pose-CT。该模型在颈部网络中引入空间和通道重建卷积,以减少空间和通道维度上的特征冗余。同时,提出了一种坐标Transformer嵌入于主干网络中,使模型专注于长距离依赖和拥有高效的局部特征提取能力。其次,通过使用无偏特征位置对齐来解决多尺度融合过程中出现的特征错位问题。最后,使用损失函数MPDIoU对边界框的回归损失重新定义。在COCO 2017数据集上的实验结果表明,本文优化的网络模型与主流的轻量级网络EfficientHRNet-H1模型相比,在保持相同精度的同时,参数量和计算量分别减少16.2%和66.1%。相比于基准模型YOLOv5s6-Pose,参数量减少11.2%,计算量降低5.8%,平均检测精度和平均召回率分别提升2.5%和2.6%。

联合关键点数据增强和结构先验的遮挡人体姿态估计

人体姿态估计技术在许多领域都有着重要的应用。现有研究主要聚焦于无遮挡情况下的人体关键点精确定位,却忽略了人像采集过程中普遍存在的遮挡问题。针对此问题,提出了一个基于关键点数据增强的人体姿态估计方法。具体地,数据增强策略以训练图像中人体可见关键点为中心,生成特定数量和大小的遮挡区域,模拟人体关键点受遮挡时的场景,提升网络模型对遮挡场景下关键点预测的鲁棒性。为了提高模型对被遮挡关键点与相邻关键点间关联性的感知,进一步设计基于人体结构先验知识的损失函数,根据人体真实结构构建相邻关键点连接关系,约束预测的关键点坐标范围,从而提升被遮挡关键点的坐标精度。在OCHuman测试集和COCO验证集上的预测结果表明,相比于基准网络模型,该方法在不增加网络参数的情况下能够提升遮挡场景中的人体姿态估计性能。

围绝经期及绝经后期女性人体体成分与腰椎骨密度的相关分析

目的探讨围绝经期及绝经后期女性人体体成分与腰椎骨密度(bone mineral density,BMD)之间的关系,进一步分析该人群骨量减少的影响因素。方法招募2021年10月至2024年3月于首都医科大学附属北京妇产医院内分泌科就诊的围绝经期及绝经后期女性300例为研究对象。采用定量电子计算机断层扫描技术(quantitative computed tomography,QCT)测量腰椎骨密度,根据测量结果分为骨量正常组和骨量减少组,采用肌肉功能分析仪测定所有受试者的体质量、脂肪、下肢肌肉、膝关节活动等人体成分情况,采用更年期症状全面评估量表采集所有研究对象的年龄、绝经状态及活动类型。采用单因素方差分析比较骨量正常组和骨量减少组的人体体成分之间的差异性,采用多因素Logistic回归分析探讨骨量减少的危险因素。结果300例研究对象中,围绝经期女性148例(49%),平均年龄(51.40±5.03)岁;绝经后期女性152例(51%),平均年龄(53.59±6.04)岁。绝经后期女性的骨密度低于围绝经期女性,差异有统计学意义(P<0.05)。骨量减少组118例(39%),骨量正常组182例(61%)。骨量减少组女性年龄、脂肪百分比、绝经后期占比和无锻炼占比均高于骨量正常组,差异有统计学意义(P<0.05);而下肢肌肉分布系数、下肢肌力和有锻炼占比均低于骨量正常组,差异有统计学意义(P<0.05)。Spearman相关性分析结果表明围绝经期和绝经后期女性BMD与年龄、脂肪百分比、绝经后期占比均呈显著负相关(r=-0.492、-0.125、-0.287,P<0.05),而与下肢肌肉分布系数、下肢肌力、有锻炼占比均呈显著正相关(r=0.143、0.180、0.193,P<0.05)。二元Logistic回归分析结果显示,年龄大、脂肪百分比大、下肢肌肉分布少、锻炼少是骨量减少的危险因素(P<0.05)。结论与围绝经期女性相比,绝经后期女性的腰椎骨密度明显降低,围绝经期及绝经后期女性腰椎骨密度与人体体成分及活动类型密切相关,其中年龄大、脂肪百分比大、下肢肌肉分布少、锻炼少是骨量减少的危险因素(P<0.05)。建议临床医生关注此时期女性的腰椎骨密度及人体体成分的变化,以便通过及时合理的干预措施来提高她们的生活质量,预防骨质疏松的发生。

檀香木提取物对皮肤嗅觉受体的影响及功效

研究旨在探讨衰老对皮肤嗅觉受体OR2AT4的影响及檀香木提取物的作用机理和人体功效。通过不同年龄的体外重建表皮模型研究了年龄和OR2AT4的关系,并建立衰老表皮模型和毛囊真皮乳头细胞模型研究了檀香木提取物对OR2AT4的激活作用,通过毛囊真皮乳头细胞模型研究了檀香木提取物促进生长期延长因子IGF-1产生的作用。同时结合人体功效测试验证其抗衰老和防脱的功效。体外试验结果表明,OR2AT4的表达水平随年龄增加而减少。经1%檀香木提取物处理后,衰老表皮模型中的OR2AT4显著提升46%。同时,0.002%檀香木提取物作用于毛囊真皮乳头细胞时,可以促进IGF-1的产生,显著提升27%。临床试验结果表明,使用含2%檀香木提取物的面部乳霜28天后,皮肤水分含量、亮度、紧致度和皱纹均有所改善。使用含2%檀香木提取物的头皮精华86天后,头发密度显著提升。综上,檀香木提取物通过激活皮肤嗅觉受体改善皮肤衰老表征及防止因毛囊缺乏活力引起的脱发问题。

基于注意力机制的人体关键点隐式建模网络

人体姿态估计任务需要利用视觉线索和关节间的解剖关系来定位关键点,但基于卷积神经网络的方法难以关注远程上下文线索和建模远距离关节之间的依赖关系。为此,提出一种基于注意力机制的隐式建模方法,通过多阶段迭代计算关节之间的特征相关性来隐式建模关键点间的约束关系,消除卷积神经网络的局部操作,扩大网络的感受野,建模远距离关节之间的依赖关系。为了解决网络在训练过程中可能弱化不可见关键点的问题,采用焦点损失函数,使网络更关注于复杂的关键点。使用目前精度最高的特征提取高分辨率网络(HRNet)和经典特征提取残差网络(ResNet)作为主干网络进行实验,结果表明,在同等实验条件下,隐式建模方法可以提高人体姿态估计网络的性能,在MPII和MSCOCO人体姿态估计基准数据集上,以HRNet网络为主干网络的算法相较于原网络,精度分别提升了1.7%和2.6%。

改进的三维人体姿态估计算法

针对目前三维人体姿态由于遮挡、姿态复杂等预测不准确的问题,提出了一种改进的三维人体姿态估计算法以获得准确的三维人体姿态,提高人体姿态估计性能.本文采用时空图注意力卷积网络中的图注意力块来构建整个网络,在此基础上对全局多头图注意力部分的网络结构进行改进,使节点间更好传播和融合信息,捕获图中没有显式表示的语义信息.同时引入运动学约束,在MPJPE损失的基础上,加上骨骼长度损失.通过对局部和全局的空间节点信息建模,实现对局部运动学连接、对称性和全局姿态的人体骨骼运动学约束的学习.通过实验证明,本文改进后的模型有效地提高了人体姿态估计性能,在Human3.6M数据集上相较于原始模型,实现了1.8%的平均关节位置误差(MPJPE)提升和1.3%的预测关节与真值关节刚性对齐后的平均关节位置误差(P-MPJPE)提升.

大气污染对人体健康影响的经济损失研究

采用修正人力资本法,分析大气污染对人体健康影响的经济损失的影响因素,估算大气污染引起的过早死亡人力资本损失和大气污染造成的慢性支气管炎发病人力资本损失,并以广东省为例,估算出大气污染对人体健康影响的经济损失约为112.1亿元。

鼻咽癌染色体3p14的精细等位基因缺失研究

目的 研究鼻咽癌染色体 3p14区域的精细等位基因杂合性丢失 (lossofheterozygosity,LOH)情况 ,并探讨LOH与鼻咽癌临床分期、临床病理和EB病毒 (Epstein Barrvirus,EBV)感染的关系。方法 采用 3p14区域 6个精确高密度的微卫星多态性位点 ,对 32例患者鼻咽癌组织进行LOH分析。结果 32例患者中有 2 3例 ( 71 9% )在至少 1个位点发生LOH ,丢失频率较高的 3个位点是D3S1313( 46 4% )、D3S130 0 ( 5 0 0 % )和D3S1312 ( 44 4% )。在具有丢失的 2 3例患者中 ,12例表现为一个连续的非随机的LOH区域 ,其最小共同缺失区为D3S1313～D3S1312。该区域的LOH与临床分期、EBV感染有明显关系。 30例低分化鳞癌的LOH频率为 70 0 % ,2例泡状核细胞癌均存在 2个位点的LOH。结论 鼻咽癌染色体 3p14区存在较高的LOH率 ,提示在D3S1313和D3S1312之间可能存在尚未克隆的与鼻咽癌发生发展相关的抑癌基因。

基于人力资本损耗计量环境污染经济损失的模型构建

基于人力资本损耗建立带有环境污染影响的人力资本存量计量模型,应用卢卡斯人力资本外部性内生生产函数,沿着环境污染—人力资本损耗—经济增长的路径,比较存在环境污染和不存在环境污染下的经济产出,可以间接衡量环境污染的经济损失,从而建立基于人力资本损耗的环境污染经济计量模型。

南海珊瑚礁经济价值评估

根据已有的基础数据、国外文献资料及野外调查资料,利用生产效益法和数值转移法估算南海珊瑚礁的经济价值(包括渔业经济价值、海岸保护价值、旅游休闲价值、生物多样性价值)以及由于过度捕捞、破坏性捕捞和陆源沉积物污染而造成其经济价值的损失。结果显示:南海珊瑚礁年经济价值为156.5亿元,其中渔业价值占90%,为140.4亿元;其次是海岸保护价值,占5.5%,为8.7亿元;而旅游休闲价值和生物多样性价值分别为5.3亿元和2.1亿元。珊瑚礁如果维持可持续利用的状态,并考虑10%的贴现率,未来20 a珊瑚礁总的经济价值为1 370亿元。由于南海珊瑚礁面临最大的威胁是人类不合理的利用,其对今后20 a珊瑚礁带来的经济损失是258.8亿元,其中因破坏性捕捞造成的损失为249.6亿元,占总经济价值损失的96.4%,而因过度性捕捞和陆源沉积物造成的经济损失分别是3.3亿元和5.9亿元。人类干扰对今后20 a南海珊瑚礁造成的经济价值损失占未来20 a南海珊瑚礁总经济价值的18.98%。

某公立医院人才流失现状及原因分析

目的了解某地级市三级甲等医院近12年人才流失原因,提出应对策略。方法通过人力资源管理信息系统导出流失人员相关信息进行分析。结果医疗、护理人员是流失人才的主要部分,其中以编外用工的初级职称护理人员和在编中高级医疗人员为主,医疗专业高学历、护理专业低学历人员流失较多。结论公立医院应优化人力资源配置,通过合理的薪酬体系、科学的职业生涯规划和富有内涵的医院文化控制人才流失。