Background: Diabetes, hypertensive heart disease, ischaemic heart disease, and cerebrovascular disease share upstream cardiometabolic pathways, but whether they increasingly form a concentrated adult mortality architecture in China remains unclear. We examined how these four causes jointly shaped mortality among Chinese adults aged 20 years and older from 2013 to 2021 and assessed implications for primary prevention centred on glycaemic and blood-pressure management. Methods: We conducted a national population-based observational analysis using aggregated mortality surveillance data for Chinese adults aged 20 years and older from 2013 to 2021. Because adult-level estimates were synthesised from harmonised 20–59-year and ≥60-year analytic layers with different age-restricted standardisation frameworks, adult structural measures were based on deaths, the percentage of all adult deaths, and the percentage of total weighted adult age-standardised mortality contribution rather than on a pooled adults-20+-only ASMR. We further characterised 2021 life-stage patterns across ages 20–39, 40–59, 60–74, and ≥75 years, and examined later-life inequalities by sex, residence, and region. Results: Combined deaths from the four causes increased from 632,869 in 2013 to 945,427 in 2021. Their share of all adult deaths rose from 44.07% to 50.15%, and their share of total weighted adult ASMR contribution increased from 43.68% to 48.23%. In adults aged 20–59 years, diabetes ASMR increased from 2.83 to 3.78 per 100,000 and ischaemic heart disease ASMR from 19.53 to 21.18, whereas hypertensive heart disease declined from 3.30 to 2.60 and cerebrovascular disease from 28.20 to 24.11. In 2021, weighted rates increased from 0.77, 0.54, 5.37, and 4.51 per 100,000 at ages 20–39 years to 7.20, 4.93, 39.14, and 46.37 at ages 40–59 years, with further escalation in later life. Conclusions: Adult mortality in China is increasingly concentrated within a cardiometabolic–vascular continuum spanning diabetes, blood-pressure-related cardiac injury, and major vascular outcomes. These findings support integrated primary prevention strategies that prioritise glycaemic management, blood-pressure control, and early vascular-risk detection across the adult life course.

Circadian rhythm disruptions have been implicated in numerous health issues, including cognitive decline and the exacerbation of neurodegenerative diseases, like Alzheimer disease (AD). Brain-derived neurotrophic factor (BDNF), vital for neuronal plasticity and cognitive function, is regulated by the circadian clock and exerts protective effects against AD. Thus, we investigated the impact of circadian rhythm disorders (CRDs) on cognitive impairment and explored the underlying neurobiological mechanisms by assessing BDNF and amyloid-β (Aβ) levels. We divided male C57BL/6 mice into three groups (n = 30): a control group (normal 12/12 hour light-dark cycle) and two CRD model groups (3/3 and 22/22 hour cycles, respectively). After 12 weeks, we assessed cognitive functions using the Morris water maze. Following behavioral tests, hippocampal levels of BDNF and Aβ were quantified using enzyme-linked immunosorbent assays. CRDs significantly impaired learning and memory, as evidenced by longer times to reach and find the platform in the CRD groups (p < 0.01). Furthermore, BDNF levels were notably decreased and Aβ levels increased in the CRD groups compared with the control group (p < 0.01). Thus, CRDs elicit cognitive impairment by reducing BDNF levels and increasing Aβ deposition in the hippocampus.

ObjectivesAnalyzing and comparing COVID-19 infection and case-fatality rates across different regions can help improve our response to future pandemics.MethodsWe used public data from the WHO to calculate and compare the COVID-19 infection and case-fatality rates in different continents and income levels from 2019 to 2023.ResultsThe Global prevalence of COVID-19 increased from 0.011 to 0.098, while case fatality rates declined from 0.024 to 0.009. Europe reported the highest cumulative infection rate (0.326), with Africa showing the lowest (0.011). Conversely, Africa experienced the highest cumulative case fatality rates (0.020), with Oceania the lowest (0.002). Infection rates in Asia showed a steady increase in contrast to other continents which observed initial rises followed by decreases. A correlation between economic status and infection rates was identified; high-income countries had the highest cumulative infection rate (0.353) and lowest case fatality rate (0.006). Low-income countries showed low cumulative infection rates (0.006) but the highest case fatality rate (0.016). Initially, high and upper-middle-income countries experienced elevated initial infection and case fatality rates, which subsequently underwent significant reductions.ConclusionsCOVID-19 rates varied significantly by continent and income level. Europe and the Americas faced surges in infections and low case fatality rates. In contrast, Africa experienced low infection rates and higher case fatality rates, with lower- and middle-income nations exceeding case fatality rates in high-income countries over time.

Background Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway.Methods A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected.Results In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone.Conclusions In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

肌肉减少症是指肌肉质量和功能随年龄增大而减少的现象〔1,2〕,随着人体年龄的增长,骨骼肌质量从30岁开始每年下降0. 1％ ～0. 5％,65 岁后显著加速,同时伴随着肌肉力量的减少〔3〕,伴有身体残疾,生活质量下降和死亡等不良后果〔4〕.肌肉减少症的原因,涉及生活习惯和年龄依赖性生物学变化,包括慢性炎症,线粒体异常,神经肌肉接头丢失,卫星细胞数量和功能减少,激素改变〔5,6〕.目前虽然对肌肉减少症临床重要性的认识有所提高,但尚无确定的治疗干预措施来有效治疗肌肉减少症,对肌肉减少症的治疗干预的实施仍然具有挑战性.本研究旨在对肌肉减少症治疗的研究进展进行综述.

Objective We examined the association between nonalcoholic fatty liver disease and lumbar spine bone mineral density in individuals with and without type 2 diabetes. Methods The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via B-mode ultrasound. Multivariable linear regression was used to study the association between NAFLD and lumbar BMD in participants with and without T2DM. Results The lumbar BMD in the T2DM group and the non-diabetes group was higher in the NAFLD group than in the non-NAFLD group ( P < 0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the positive association between lumbar spine BMD and NAFLD remained ( P = 0.027). In the non-diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared. Conclusions The relationship between nonalcoholic fatty liver disease and lumbar bone mineral density may differ in individuals with and without diabetes. The effect of nonalcoholic fatty liver disease on bone mineral density needs to be evaluated in different clinical contexts.

硬化蛋白(sclerostin,Scl)在骨代谢中发挥重要作用,大量动物实验及临床试验证实抑制硬化蛋白能改善骨结构、增加骨密度.硬化蛋白单克隆抗体Romosozumab(ROMO)已在美国和加拿大批准上市,是目前唯一一个兼具促进骨形成与抑制骨吸收双重作用的抗骨质疏松药物,但其不良反应与治疗期间表现的时间依赖性是目前存在的两大问题.因此,期待可以通过硬化蛋白研发出治疗效果更好、不良反应更少的新型抗骨质疏松症药物.因此,笔者介绍了目前对sclerotin的结构、表达及作用机制的认识,深入探讨了其发挥作用的分子靶点,以期能为未来药物研究提供新方向.还综述了硬化蛋白对骨骼系统中不同细胞的具体作用,分别叙述了其在破骨细胞(osteoclast,OC)、成骨细胞(osteoblast,OB)以及骨髓脂肪细胞的作用,并提出了未来应着力研究的方向.

Abstract Objective: To evaluate the association between Nonalcoholic fatty liver disease (NAFLD) and lumbar spine bone mineral density (BMD) in type 2 diabetes mellitus (T2DM).Methods: The lumbar BMD of 1088 subjects was measured using dual-energy X-ray absorptiometry (DXA). Liver fat content was quantified via ultrasound. According to clinical diagnosis, subjects were divided into T2DM and non diabetes groups. The groups were further divided into NAFLD and non- NAFLD groups. Student’s t-test assessed the differences in BMD between the NAFLD and non-NAFLD groups. Multivariable linear regression analysis adjusted for confounders was performed to evaluate the association between lumbar BMD and NAFLD. Results: The lumbar BMD in the T2DM group and the non diabetes group was higher in the NAFLD group than in the non-NAFLD group (P<0.001). Multivariate regression analysis in the T2DM group showed that after adjusting for confounders, the association between lumbar spine BMD and NAFLD remained (P=0.027). In the non diabetes group, after adjusting for confounders, the association between NAFLD and lumbar spine BMD disappeared. Conclusions: The lumbar BMD of NAFLD patients is higher than that of non-NAFLD. After adjusting for confounding factors, lumbar BMD was associated with NAFLD in T2DM patients but not in non diabetes patients.

The reduced density of cardiac autonomic nerves plays an important role in malignant arrhythmia after myocardial infarction (MI). Previous studies have shown that there is an interaction between the brain and the heart, and fastigial nucleus electrostimulation (FNS) promotes central nerve regeneration. Whether and how it can promote cardiac nerve regeneration after MI and the underlying mechanisms remain unknown. This study investigated whether FNS promotes cardiac nerve regeneration and reduces malignant arrhythmia inducibility in a post-infarction rat model. Ninety-eight Wistar rats were randomly assigned to Sham control, MI (left anterior descending coronary artery ligation without FNS), FNS (MI plus FNS), and FNL (fastigial nucleus lesion plus FNS plus MI) groups. The frequency of malignant arrhythmia was significantly lower in the FNS group than in the MI and FNL groups. The density of cardiac autonomic nerves was less in the MI group than in the Sham group, which was promoted by FNS. The nerve growth factor (NGF) mRNA expression was downregulated in the MI group compared to the Sham group, which was significantly enhanced by FNS. The expression levels of norepinephrine (NE) and acetylcholine (ACh) were higher and lower respectively in the MI and FNL groups than in the Sham group. After FNS, NE concentration was reduced and Ach level was elevated compared to the MI group. These data suggested that FNS promoted the regeneration of cardiac autonomic nerves and reduced the incidence of malignant arrhythmias in MI rat model. The mechanisms might involve up-regulation of NGF mRNA expression, decrease of NE release and increase of ACh release.

阿尔茨海默病( AD)是常见的痴呆形式,占老年痴呆病人的60％ ～80％ 〔1〕,主要表现为进行性记忆力和认知功能下降,死亡常常发生在诊断后几年内, AD的不可逆神经元功能障碍和致残将会造成巨大的社会经济负担,将成为全球最大的公共卫生挑战之一,迫切需要新的治疗方法.针对β淀粉样蛋白(Aβ)产生,聚集或其从脑中清除已成为预防或治疗AD 的活跃研究领域.Aβ 是由淀粉样前体蛋白( APP)代谢产生,APP可被α-分泌酶的神经外蛋白酶切割,产生可溶性细胞外片段( sAPPα) ,被 β-分泌酶( BACE1 ) 切割,产生可溶性细胞外片段( sAPP+)和细胞膜结合片段( C99 ) ,细胞膜结合片段在细胞内被γ-分泌酶裂解,释放淀粉样蛋白细胞内结构域和Aβ,Aβ 聚集形成寡聚体,原纤维和斑块.在AD中,Aβ浓度的变化出现在脑脊液( CSF)中,依次是脑Aβ 积聚, CSF增加,海马和灰质体积减少,葡萄糖代谢减少,记忆障碍和痴呆〔2,3〕.Aβ不仅在脑细胞中表达,也在神经元,星形胶质细胞和小胶质细胞中表达,还在外周器官和组织,例如肝肾胰脾等脏器及各种血液和内皮细胞中表达.本文对近年有关Aβ清除及针对该机制的治疗策略进展进行综述.

Background: Findings from recent meta-analyses of anti-osteoporosis drugs have shown that there is no association of anti-osteoporosis drugs with overall mortality, possibly because of population limitations such as age, sex, the presence or absence of fractures, and other parameters, which are associated with increased mortality in the elderly. There is no report about possible associations between anti-osteoporosis drugs and overall mortality in the old (ages ≥ 50 years) or oldest (ages ≥ 75 years) population. The purpose of using anti-osteoporosis drugs is not only to improve bone mineral density and reduce fractures, but also to prolong life expectancy, especially in the old or oldest population. We determined the association between anti-osteoporosis drugs and overall mortality in the old and oldest populations, and determined the effects of different demographic parameters.Methods: We searched Web of Science, Embase, the Cochrane Database, and PubMed from inception to January 10, 2021, for trials reporting the effects of anti-osteoporosis drugs on overall mortality. The effects of calcium and vitamin D were excluded. We included all randomized trials comparing interventions with different anti-osteoporosis drugs, and we included elderly (ages ≥ 50 years) without other metabolic bone diseases. We pooled data using a fixed effects meta-analysis with weighted mean differences and reported 95% confidence intervals (CIs). We also used the I² statistic to assess heterogeneity in the results of individual studies. The primary endpoint was the total number of people in the drug treatment and placebo groups, and the number of deaths during the follow-up periods. Findings: Of 23,242 citations identified by the search strategy, 25 studies (mean duration: 3.0 years, comprising 93,782 participants; 91.4% women; average age: 73.2 years) met the inclusion criteria. A total of 21 studies were mainly comprised of Caucasians. In 25 studies, anti-osteoporosis drugs included bisphosphonate, selective estrogen receptor modulators (SERMs), parathyroid hormone analogues, receptor-activated nuclear factor-κB ligand inhibitor, anti-sclerostin antibodies. and strontium ranelate. One of the studies used two anti-osteoporosis drugs compared with placebos, while all the other studies used one anti-osteoporosis drug.In the elderly population, anti-osteoporosis drugs did not reduce individual mortalities (weight RR: 0.96; 95% CI: 0.90–1.02), with heterogeneity among trials (I² = 2%, p = 0.43); however, none of the anti-osteoporosis drugs was significantly associated with overall mortality. Stratified analyses were performed according to age and sex, with osteoporosis, and with or without fractures. In different age groups (> 65 years of age, > 75 years of age, and > 80 years of age), the associations between anti-osteoporosis drugs and overall mortalities were not significant. In the female and male groups, none of the associations between anti-osteoporosis drugs and overall mortality were significant. In the with or without osteoporosis groups, these drugs did not reduce overall mortalities. However, these drugs did show reduced mortality (RR: 0.83; 95% CI: 0.70–0.99), but only in the group with fractures.Interpretation: None of the anti-osteoporosis drugs reduced overall mortality, but in the old population with recent fractures, these drugs showed a reduced overall mortality. The association between anti-osteoporosis drugs and overall mortality did not influence by age and sex. The use of these drugs in the old and oldest populations was safe, and was effective in patients with fractures.Funding Statement: This work was supported by grants from the Chongqing Health and Family Planning Commission (No. 2015MSXM016), Chongqing Development and Reform Commission (No. [2013] 1420), and National Key Clinical Specialties Construction Program of China (No. [2013] 544).Declaration of Interests: None.

Background & aims: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. Methods: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. Results: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 mu g/mL vs 1.00 mu g/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (beta: -0.164, p = 0.008), and muscle strength (beta: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 mu g/mL, respectively. Conclusions: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner. (C) 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

This is a brief case report focused on the neuropsychological test scores of a man who suffered two separate brain injuries. His first injury was to the left side of his head when he struck a rock with his head when ocean diving. Approximately 5 years later neuropsychological testing was done as he had lost his job selling technical equipment and had difficulties in functioning on a daily basis. The testing showed clear signs of significant impairment to the left, cerebral hemisphere.

目的:探讨中枢神经特异蛋白(Soluble protein-100β,S100β)和神经元特异性烯醇化酶(Neuron specific enolase,NSE)水平预测急诊高血压脑出血患者预后的价值.方法:回顾性分析我院2018年04月至2019年07月期间急诊入院的190例高血压脑出血患者血清S100β蛋白和NSE水平,统计患者入院后30天的病死率.采用Pearson分析血清S100β蛋白、NSE水平与预后的相关性;以ROC曲线评估血清S100β蛋白和NSE水平单独和联合预测高血压脑出血患者的预后.结果:Pearson相关性分析结果显示患者血清S100β蛋白与NSE含量呈正相关(r=0.16,P<0.05).ROC曲线显示:S100β、NSE均可单独预测患者预后,而预测的准确性依次为:S100β>(S100β+NSE)=NSE.结论:S100β、NSE作为生物学指标可以预测患者预后,S100β准确性更高.

妊娠哺乳相关骨质疏松症(pregnancy and lactation associated osteoporosis,PLO)是一种罕见的疾病,主要发生在妊娠晚期和产后早期妇女,常在第一次妊娠时发病,以胸腰椎多发压缩性骨折最常见,主要表现为腰背疼痛、身高变矮、活动受限.其发病机制目前尚不清楚,可能与妊娠、哺乳状态、遗传因素等相关.在怀孕期间,通过肠道钙吸收的加倍以满足胎儿及母体对钙的需求,但如果母亲摄入的钙不足,不能满足母亲和胎儿的综合需求,母亲的骨骼会通过PTHrP(parathyroid hormone-related peptide,PTHrP)刺激骨骼吸收.哺乳期,在高水平PTHrP的主导作用和低雌激素的共同作用下,促进骨吸收动员骨钙入血.目前PLO尚无统一的诊断标准,防治措施尚无定论.现有研究表明大多数PLO患者在断奶后骨量逐渐增加,因此对PLO患者建议停止哺乳并补充充足钙剂及维生素D.有报道双膦酸盐、迪诺赛麦、特立帕肽等抗骨质疏松药物治疗PLO,但其存在或潜在的不良反应,使用受到限制;椎体成形术和后凸成形术等用于治疗产后椎体骨折整体疗效尚不明确,一般不推荐使用.对PLO患者需充分评估患者情况慎重选择治疗方案.

This protocol for a Cochrane Review has been withdrawn by the Cochrane Common Mental Disorders Group. The protocol was first published in 2010. Unfortunately, the authors have not been able to progress with converting this protocol into a full Cochrane Review. New authors are sought to take over this protocol.

肌肉减少症是一种与年龄有关的肌肉力量下降和躯体功能受限的老年综合征,老年人出现跌倒、身体残疾、住院和早逝等不良后果风险增加.人均寿命延长导致老龄化,肌肉减少症的发病率和患病率明显升高.2016年国际卫生组织将其纳入《国际疾病分类第十次修订版:临床修改》(ICD-10-CM),疾病编码为M62.84.目前肌肉减少症最常用的定义是欧洲老年人肌肉减少症工作组(EWGSOP)提出的,表示与增龄相关的进行性的全身肌肉量减少、肌肉强度下降或肌肉生理功能减退,2019年EWGSOP更新肌肉减少症定义.肌肉减少症被认为是晚年负面健康结果的相关决定因素,肌肉力量和活动能力的丧失导致躯体平衡障碍,老年人发生跌倒和骨折的比率升高,增加社会残疾率及医疗负担,明确病因十分重要.近年来国内外学者研究发现肌肉减少症与运动因素、内分泌因素、慢性炎症、营养状况、肠道菌群、遗传因素及社会心理素等相关,但具体病因尚不明确.本文通过查阅大量有关文献,对肌肉减少症病因学研究现状与进展作一综述.

目的:通过胰岛素抵抗稳态模型评估法(Homeostasis model assessment of insulin resistance,HO-MA2-IR)探讨肌肉减少症与胰岛素抵抗的关系.方法:将2014年6月至2016年1月我院收治的60岁以上并完成了双能X线吸收仪(Dual-energy X-ray absorptiometry,DXA)检查 、双上肢握力及6米步行速度测试的患者分为肌少症组及对照组两组,两组分别测定糖化血红蛋白,空腹血糖 、空腹胰岛素或C肽并计算出HOMA2-IR指数,比较肌少症组与对照组的相关指标.结果:与对照组比较,肌少症组的HOMA2-IR值更高(P<0.05).HOMA2-IR指数与握力 、6米步行速度显著负相关(P<0.01),与四肢肌肉量/身高的平方负相关(P<0.05).Logistic回归分析提示肌少症与HOMA2-IR存在独立相关性(P<0.05).结论:肌少症发病与胰岛素抵抗之间存在独立相关性,治疗肌少症可能改善患者胰岛素抵抗.

目的 探讨抗骨质疏松药物干预联合骨关节护理对绝经后骨质疏松伴腰背痛患者疼痛程度和生活质量的临床疗效.方法 选取2018年1月～2018年10月期间绵阳市第三人民医院妇科收治的70例绝经后骨质疏松伴腰背痛患者,按随机数字表法分为对照组和观察组,每组各35例.对照组给予常规止痛药物干预和常规护理,观察组在常规护理基础上给予抗骨质疏松药物干预加骨关节护理.1月后对比分析两组患者的疼痛情况以及生活质量.结果 干预1月后两组患者疼痛程度和生活质量均有显著改善(P＜0.05);与对照组比较,观察组疼痛程度降低更显著(P＜0.05),生活质量评分升高更明显(P＜0.05).结论 抗骨质疏松药物治疗联合骨关节护理对绝经后骨质疏松伴腰背痛的女性疼痛程度减轻和生活质量提高效果显著优于常用止痛药物加常规护理,可在临床推广应用.