正常机体通过人体各器官和系统相互协调和生理反馈,维持内环境的相对稳定;内脏器官功能损害、器官之间协调作用失代偿与内环境稳态失衡之间互相影响,互为因果;不同个体、不同年龄段及不同伤害程度等机体的稳态系统的稳定域存在差异,稳定域越宽说明系统的自稳定性越好,自我纠偏能力越强.老年患者往往"多病共存"、器官功能下降等导致稳态系统稳定域差异较大,再喂养综合征、衰弱等老年综合征是机体维持稳态能力下降的表现.该文从内环境稳态角度出发,提出老年病干预方法及预后判断,防止医源性内环境稳态失衡.

This study aimed to investigate the effects and mechanisms of osteocalcin on autophagy in myoblasts, as well as its possible therapeutic effects in aging muscle. Starved murine myoblast C2C12 cells with or without interleukin (IL)-6 siRNA were treated with osteocalcin. Expression of the autophagy protein marker LC3, as well as IL-6 and phosphorylated STAT3 were detected by immunoblotting, immunofluorescence, or immunohistochemistry. Autophagosomes were observed with transmission electron microscopy. Levels of reactive oxygen species (ROS) were detected by flow cytometry. Fasted young mice were injected intraperitoneally with osteocalcin, with or without the JAK inhibitor CP-690550 to inhibit IL-6 signaling. Older mice were treated with osteocalcin and muscle mass, grip strength and muscle structure were assessed. The results revealed that compared to control and serum-starved cells, osteocalcin treatment significantly increased the relative expression of LC3-II/LC3-I protein, the numbers of autophagosomes, and levels of intracellular ROS. Osteocalcin injection in mice also resulted in increased relative LC3-II/LC3-I protein expression and autophagosome numbers. Osteocalcin treatment significantly increased the secretion of IL-6 in muscle cells and tissue, and activated STAT3 signaling. Moreover, knockdown of IL-6 or blocking IL-6 signaling inhibited the phosphorylation of STAT3, and further inhibited autophagy in starved myoblasts and fasting-treated murine muscle tissue. In addition, osteocalcin treatment significantly increased muscle mass and grip strength in both aged mice and aged fasting mice. In conclusion, the inhibition of osteocalcin on muscle cell aging is accompanied by the induction of IL-6-STAT3-dependent autophagy, indicating osteocalcin might be a promising therapeutic candidate for aging-related myopathies.

Supplemental Figure 1. Th17 cells are not induced in the lung after the tumor cell challenge. Supplemental Figure 2. No significant difference in the production of IFN-gamma by NK cells in the Abt mice compared with the control.

Supplemental materials and methods

Background Depressive symptoms and mild cognitive impairment (MCI) are highly prevalent in rural China. The study aimed to investigate the longitudinal associations between changes in depressive symptoms and cognitive decline and MCI incidence among Chinese rural elderly individuals. Methods A 2-year follow-up study was conducted among 1,477 participants from the Anhui Healthy Longevity Survey (AHLS). Depressive symptoms were assessed by the 9-item Patient Health Questionnaire (PHQ-9), and cognitive status was evaluated by the Mini Mental State Examination (MMSE). Multivariable linear regression and logistic regression were employed. Results Every 1-unit PHQ-9 score increase was significantly associated with more cognitive decline (β = 0.157, 95% CI: 0.092, 0.221, p < 0.001) and a higher risk of MCI incidence (OR = 1.063, 95% CI: 1.025, 1.103, p = 0.001). The participants who experienced worsening of depression symptoms had a larger decline in the 2-year MMSE score (β = 0.650, 95% CI: 0.039, 1.261, p = 0.037) and elevated risks of incident MCI (OR = 1.573, 95% CI: 1.113, 2.223, p = 0.010). Limitations Screening tools rather than standard diagnostic procedures were used in the study. Moreover, the long-term associations still need further exploration since the follow-up time was short. Conclusions Increased depressive symptoms were associated with more cognitive decline and higher risks of incident MCI among Chinese rural residents.

慢性病是我国居民的主要致死原因,随着我国人口老龄化趋势进一步加重,慢性病的死亡占比必将进一步升高.该文就近年来我国居民的主要致死性慢性病,如卒中、缺血性心肌病、呼吸系统肿瘤、慢性阻塞性肺疾病、消化系统肿瘤、阿尔茨海默病及其他痴呆症等进行分析;了解其近几十年来的总体死亡趋势及流行病学特点,并提出相应的应对策略.

目的 研究共生菌对小鼠肺脏组织中核转录因子κB(NF-κB)、抑制性κB激酶α/β(IKK-α/β)及磷脂酰肌醇3-激酶(PI3K)等信号通路分子表达的调控作用.方法 用Western blot方法检测共生菌缺失小鼠(Abx鼠)及正常小鼠(WT鼠)肺脏组织中NF-κB、IKK-α/β及PI3K等的表达量及其磷酸化水平,并进行分析比较.结果 小鼠缺失共生菌后,其肺脏组织中NF-κB表达上调(Abx比WT,1.609±0.084比1.000±0.000;t=7.287,P＜0.01),NF-κB磷酸化水平上调(Abx比WT,2.039±0.133比1.000±0.000;t =7.812,P＜0.01),IKK-α表达无明显变化(Abx比WT,1.206±0.095比1.000±0.000;t =2.170,P=0.055),IKK-β表达上调(Abx比WT,3.389±0.184比1.000±0.000;t 13.012,P＜0.01),IKK-α/β磷酸化水平上调(Abx比WT,1.433±0.053比1.000±0.000;t=8.203,P＜0.01),PI3K表达上调(Abx比WT,1.414±0.024比1.000±0.000;t=17.206,P＜0.01),PI3K磷酸化水平上调(Abx比WT,3.171±0.237比1.000±0.000;t=9.160,P＜0.01).结论 共生菌对小鼠肺脏组织中NF-κB、IKK-α/β及PI3K等的表达量及其磷酸化水平均有重要的调控作用.

目的 了解老年慢性便秘患者营养、精神心理、认知及生活质量的情况.方法 纳入老年内科住院患者160例,根据罗马Ⅳ诊断标准和患者主诉对慢性便秘进行诊断.慢性便秘的患者为85例,非慢性便秘患者75例.患者入院时采用微型营养评估量表(MNA)进行营养状态评估,采用老年抑郁量表(GDS)和汉密尔顿焦虑量表(HAMA)评估所有患者的抑郁和焦虑情绪,采用简易智能评估量表(MMSE)筛查所有患者认知功能,并采用便秘患者生存质量自评量表(PAC-QOL)评估所有患者的生活质量.对慢性便秘患者进行单因素及多因素logistic回归分析.记录所有便秘患者的便秘相关用药等情况,并出院时再次对其进行PAC-QOL评分.结果 老年慢性便秘患者与非便秘的老年患者相比较,MNA评分偏低,但差异无统计学意义;GDS评分[(15.2±4.2)分比(9.8±1.6)分,P<0.01]、HAMA评分[(13.8±4.4)分比(10.1±1.9)分,P<0.01]和PAC-QOL量表评分[(78.6±14.8)分比(50.9±12.5)分,P<0.01]均较高,差异有统计学意义;而MMSE评分较低[(16.6±4.1)分比(23.9±3.5)分],差异有统计学意义(P<0.01).单因素分析结果显示,存在焦虑情绪(χ2=20.51,P<0.01)、抑郁情绪(χ2=30.15,P<0.01)、认知障碍(χ2=21.80,P<0.001)、平素服用5种以上药物(χ2=32.09,P<0.01)以及合并3种以上慢性疾病(χ2=10.53,P<0.01)均增加了老年慢性便秘发生的风险.logistic回归分析结果显示,焦虑状态(OR=9.507,95％CI:3.048～29.654,P<0.01)、抑郁状态(OR=5.922,95％CI:2.510～13.975,P<0.01)和多重用药(OR=4.765,95％CI:2.037～11.143,P<0.01)均增加了老年慢性便秘发生的风险.结论 老年慢性便秘患者易合并有焦虑抑郁情绪障碍,且生活质量下降明显.积极认识并干预可能导致慢性便秘的各种危险因素,综合管理老年便秘患者的身心健康及认知等,可能有利于提高老年慢性便秘患者的生活质量.

Sarcopenia, an age-related geriatric syndrome characterized by progressive decline in skeletal muscle mass and strength, is a major factor leading to disability, decreased quality of life, increased nursing needs, and increased medical costs in the elderly.In recent years, several consensus groups have revised the diagnosis of sarcopenia and assigned diagnostic cut-offs and emphasized the importance of muscle strength, however, the diagnostic criteria and diagnostic cut-offs have not been fully unified on a global scale.In addition, more and more research efforts are devoted to elucidating the underlying mechanism of sarcopenia, but the prevention and treatment of sarcopenia is still limited to lifestyle intervention and supplementation of nutrition combined with exercise.This article reviews the diagnosis, treatment and prevention of sarcopenia.It is expected that there will be a more complete system in the future, which will help to identify patients with sarcopenia as early as possible and actively intervene and treat them, so as to reduce the adverse outcomes of patients and reduce the heavy burden on the health care system.

Objective:To evaluate the clinical efficacy and safety of fecal microbiota transplantation(FMT)for the treatment of chronic functional constipation in the elderly.Methods:A total of 33 elderly patients with chronic functional constipation were included and given three sessions of FMT.Changes in fecal characteristics, constipation, mood and quality of life in these patients were evaluated using the Bristol stool form scale(BSFS), the constipation assessment scale(CAS), patient assessment of constipation symptoms(PAC-SYM), the Zung self-rating anxiety scale(SAS), the Zung self-rating depression scale(SDS), and the patient assessment of constipation quality of life(PAC-QOL)before and 12 weeks after treatment.The clinical efficacy was based on comparison between pre-and post-treatment results for each patient.Results:Clear improvement was achieved in 33 patients 12 weeks after treatment, compared with before transplantation.Post-treatment scores of the constipation assessment scale and symptom self-assessment questionnaire for patients with constipation were(8.9±1.2)scores and(26.5±2.4)scores, respectively, significantly lower than pre-transplantation scores of(12.2±1.1)scores and(32.4±2.4)scores( t=15.034, 13.904, both P<0.001). Similarly, post-treatment scores were also lower than pre-transplantation levels for the self-rating anxiety scale[(50.4±8.4)scores vs.(57.5±9.0)scores, t=10.333, P<0.001], the self-rating depression scale[(50.6±8.4)% vs.(55.0±10.5)%, t=5.301, P<0.001], and self-assessment questionnaire for quality of life[(88.2±7.3)scores vs.(103.7±7.3)scores, t=23.300, P<0.001]. Conclusions:FMT can improve fecal characteristics and constipation symptoms, relieve anxiety and depression, improve the quality of life, and provide a new option for the treatment for elderly patients with chronic functional constipation.

目的:分析并比较流式细胞术免疫分型和病理骨髓活组织检查非霍奇金淋巴瘤(NHL)骨髓侵犯的诊断价值.方法:初诊淋巴瘤的标本253例分别作流式细胞术免疫分型和病理骨髓活检,以临床综合诊断为金标准,分析2种方法的敏感度和特异度等检验效能,并对不同亚型NHL进行分类,分析不同检测方法的骨髓侵犯发生率.结果:流式细胞术检测骨髓侵犯发生率的灵敏度为91.67％(88/96),高于病理骨髓活检的82.29％(79/96),但差异无统计学意义(χ2=0.16,P>0.05),2种方法的特异度均为100.00％(157/157).套细胞淋巴瘤的骨髓侵犯发生率较高,分别为84.00％(金标准)、80.00％(流式细胞术)和68.00％(病理骨髓活检),弥漫大B细胞淋巴瘤的骨髓侵犯发生率较低,分别为23.75％(金标准)、22.50％(流式细胞术)和22.50％(病理骨髓活检);慢性淋巴细胞白血病/小细胞淋巴瘤的病理骨髓活检与金标准相比,差异有统计学意义(P<0.01);套细胞淋巴瘤、慢性淋巴细胞白血病/小细胞淋巴瘤、滤泡细胞淋巴瘤、B-NHL未分类的骨髓侵犯率,流式细胞术较病理骨髓活检为高,而T/NK细胞淋巴瘤,流式细胞术检出的骨髓侵犯率偏低.结论:流式细胞术对于NHL的检验效能较高,是一种灵敏、高效的检测方法.

目的 探讨N6-甲基腺嘌呤(m6 A)去甲基酶肥胖相关蛋白(FTO)在乳腺癌细胞对曲妥珠单抗耐药中的作用及新型抗人表皮生长因子受体2(HER2)人源化A21抗体(HuA21)对耐药性乳腺癌细胞增殖的影响.方法 制备曲妥珠单抗耐药细胞株(BT474/TR),光学显微镜观察BT474/TR与BT474细胞形态,四甲基偶氮唑盐(MTT)法检测细胞增殖,免疫荧光法检测增殖相关抗原(Ki67)表达,流式细胞术检测细胞周期,qPCR和Western blot法检测FTO与甲基转移酶样蛋白3抗体(METTL3)表达.结果 BT474/TR出现细胞核固缩、伪足消失,细胞增殖速度下降.曲妥珠单抗处理BT474不同时间至形成耐药细胞,Ki67表达逐渐降低(P<0.05),S期细胞比例逐渐减小(P<0.05),FTO表达逐渐增加(P<0.05),但是METTL3表达没有变化.FTO抑制剂甲氯芬那酸乙酯(MA2)促进BT474/TR细胞增殖,且提高其对曲妥珠单抗的敏感性(P<0.05).HuA21抗体对BT474/TR细胞增殖具有抑制作用(P<0.05),且联合MA2和曲妥珠单抗对BT474/TR细胞抑制效果更好(P<0.05).结论 HER2阳性乳腺癌细胞FTO基因表达与其对曲妥珠单抗耐药之间存在相关性,抑制FTO活性可以增强乳腺癌耐药细胞对曲妥珠单抗治疗的敏感性;HuA21抗体对曲妥珠单抗耐药性乳腺癌细胞有抑制作用.

Objective:To explore the clinical value of the geriatric potentially inappropriate medication(PIM)evaluation system in elderly inpatients.Methods:As a prospective cohort study, 203 elderly inpatients with polypharmacy were randomly divided into the control group and experimental group.Geriatric PIM evaluation system(based on the criteria for judging potential inappropriate drug use in Chinese elderly 2017 edition)on wechat platform was applied to patients of experimental group.During the 6 months, the number of elderly syndromes, types of drugs, the days in hospitalization, readmission rates and all-cause mortality were compared between two groups.Results:The age of 203 elderly inpatients ranged from 60 to 94(77.30±10.34)years, including 121 males and 82 females.The morbidity proportion of top five diseases were 69.95%(142/203)in cerebral infarction(non-acute phase), 62.07%(126/203)in hypertension, 24.14%(49/203)in coronary heart disease, 9.85%(20/203)in atrial fibrillation, and 6.40%(13/203)in cardiac insufficiency.The 97.53%(198/203)of elderly hospitalized patients had at least one senile syndrome, the average was 4.3±2.0.Insomnia, fall and frailty accounted for 32.87%(15/198), 28.45%(56/198)and 13.66%(27/198)respectively.Compared with the control group, the average length of stay in hospital in the experimental group significantly decreased[(16.38±4.29) vs.(21.32±6.10)d, t=2.438、 P=0.025], the number of senile syndrome, the score of fall, weakness and the re-admission rate were also decreased significantly(3.11±2.14 vs.4.32±1.50, t=0.854、 P=0.032; 6.19±1.35 vs.8.61±3.22, t=4.078、 P=0.044; 3.94±1.92 vs.5.65±1.34, t=2.843、 P=0.038; 9.81%(10/102) vs.1.98%(2/101), χ2=4.772、 P=0.029), and the frequency of PIM was significantly different between two groups(417.36±49.21 vs.210.25±38.23, t=2.136、 P=0.034). Conclusions:After making the drug adjustment on the elderly inpatients with multiple drugs, PIM evaluation system for the elderly are able to reduce the incidence of geriatric syndrome, shorten the length of stay in hospital, improve the rational use of drugs, and enhance the quality of life of the elderly patients.

Dear Editor, Signal transduction takes the responsibility of translating extracellular information into specific cellular activities,enabling cells,including cancer cells,to respond exquisitely to extracellular guidance cues.N6-methyladenosine(m6A),the most pervasive and abundant modification within eukaryotic mRNAs,is known to have specific effects on cellular activities relevant to cancer.1 Despite the fact that m6A methylation is a dynamic event involving a series of enzymes,it remains unknown whether signal transduction,much less extracellular signaling molecules,uses m6A methylation as an effector mechanism in cancer.

目的 通过对冠心病和脑卒中患者的CYP2C19基因多态性进行分析,为临床血小板聚集抑制剂的个体化应用,推进精准药物治疗提供依据.方法 采用实时荧光定量RT-PCR对4270例冠心病患者和141例脑卒中患者的基因型和代谢型进行分析.统计每种基因型和代谢型的分布情况,并探讨不同性别、不同年龄以及不同病种之间的基因型和代谢型是否具有统计学差异.结果 冠心病患者中,男性、女性人群基因型分布前3位分别为*1/*1、*1/*2、*2/*2型,以及*1/*2、*1/*1、*2/*2型,中青年与老年人群的基因型分布前3位均分别为*1/*1、*1/*2、*2/*2型;不同性别、不同年龄人群代谢型均为中代谢型最多.脑卒中患者中,男性、女性人群基因型分布前3位分别为*1/*1、*1/*2、*1/*3型,以及*1/*1、*1/*2、*2/*2型,中青年与老年人群的基因型分布前3位均分别为*1/*1、*1/*2、*2/*2;不同性别、不同年龄人群代谢型均为快代谢型最多.不同病种之间的基因型分布前3位均分别为*1/*1、*1/*2、*2/*2型,冠心病人群代谢型为中代谢型最多,脑卒中人群代谢型为快代谢型最多.以上年龄组、性别组之间均无统计学差异(P>0.05).结论 冠心病和脑卒中患者存在基因多态性,建议临床使用氯吡格雷等血小板聚集抑制剂之前进行CYP2C19基因型检测,避免出现氯吡格雷抵抗.

随着高通量测序技术的发展,越来越多的研究认为肠道菌群及其代谢产物可以通过多种途径调节免疫系统,在维持宿主免疫稳态中发挥重要作用.肠道菌群可以直接或通过代谢产物间接参与消化系统、内分泌系统、风湿系统及神经系统等多系统免疫性疾病的发生发展.因此探讨肠道菌群与免疫的关系,对进一步认识疾病,以及肠道菌群作为靶点的免疫治疗具有潜在意义.

心力衰竭是心血管相关疾病的终末期表现和主要死亡原因之一,临床上是以呼吸急促和疲乏为典型特点的一组综合征.尽管心力衰竭是一种不可逆且难以治愈的病症,却也能通过早期预防并经过合理的药物治疗与管理延缓其发生发展.该文系统回顾心力衰竭的流行病学现状、相关病因和危险因素、治疗策略变迁以及预防措施,旨在明确心力衰竭的早期预防、早期诊断、规范治疗、医患协作、全程动态监测与评估的重要性,从而降低心力衰竭患者的病死率,改善预后以及个体生活质量.

Background: beta-Arrestins have been found to regulate cell proliferation, invasion and migration; transmit antiapoptotic survival signals; and affect other characteristics of tumours. However, their role in gastric cancer (GC) is not clear. We investigated the role and mechanism of beta-arrestins in the regulation of GC. Methods: We first examined beta-arrestins mRNA levels in 17 pairs of GC tissues by qRT-PCR. We also used immunohistochemistry to further examine the expression of beta-arrestins in 60 paraffin-embedded primary GC tissues and 20 normal gastric tissues. Then, the function of beta-arrestin1 was investigated in vitro and in vivo. Results:beta-Arrestin1 was upregulated in GC tissue and was associated with tumour stage, lymph node metastasis, invasion depth and patient sex. High expression of beta-arrestin1 expression predicted poor prognosis in GC. beta-Arrestin1 promoted GC cell proliferation, migration and invasion, and it suppressed E-cadherin expression and upregulated Vimentin expression via AKT/ERK signalling pathway. The in vivo metastasis assays showed that knockdown of beta-arrestin1 reduced lung metastasis and inhibited EMT. Conclusion: The upregulation of beta-arrestin1 predicts poor prognosis and promotes metastasis and epithelial-mesenchymal transition in GC through AKT/ERK signalling pathway. This study may provide therapeutic advances for the treatment and early diagnosis of patients with metastatic GC.

目的 分析老年高血压患者认知功能障碍的影响因素.方法 选取2019年3月至10月就诊于我院的150例高血压患者作为研究对象,根据MMSE评分将其分为认知功能正常组(86例)和认知功能障碍组(64例).收集并分析两组患者的临床资料,采用多因素Logistic回归分析探讨老年高血压患者认知功能障碍的影响因素.结果 150例高血压患者的平均MMSE评分为(24.11±3.81)分,其中认知障碍64例,认知障碍发生率为42.67％.两组的SBP、LDL水平、PSQI评分比较,差异具有统计学意义(P<0.05).多因素Logistic回归分析结果显示,SBP、睡眠障碍是影响老年高血压患者认知功能障碍的独立危险因素(P<0.05).结论 高SBP、睡眠障碍是老年高血压患者认知功能障碍的独立危险因素,临床上需针对这些因素进行干预,延缓认知功能障碍的发生及发展.

机体黏膜组织中存在着大量的"共生菌",共生菌及其代谢产物不仅是机体维持免疫稳态所必需,并可影响机体对多种免疫介导性疾病的易感性.肺泡巨噬细胞是肺泡腔表面分布最为丰富的固有免疫细胞,在肺脏免疫应答及相关疾病发生发展中发挥重要作用.呼吸道及肠道菌群均可对肺泡巨噬细胞的表型及功能产生调控作用,共生菌缺失可以导致肺泡巨噬细胞的比例和数量发生变化,并影响肺泡巨噬细胞的功能和极化状态.长链非编码RNA是巨噬细胞免疫稳态和功能的重要调控分子,可以调控巨噬细胞的炎性反应及极化等,同时机体lncRNA的表达亦受共生菌信号的影响.