Objective To analyze the cognitive function and sleep quality of the elderly in Shanghai community,and explore the related influencing factors.Methods A stratified cluster random sampling method was used to select 8 community health centers in Shanghai for a questionnaire survey,including 3 677 elderly individuals who completed the"Comprehensive Health Status Survey of Elderly Residents in Shanghai"from September 2023 to November 2023.Basic information of the elderly was collected,including age,gender,education level,smoking,drinking,mahjong playing behavior,and exercise habits.The Pittsburgh sleep quality index(PSQI)was used to assess the sleep quality of the elderly,subjective cognitive decline(SCD)self-assessment questionnaire and Mini-Mental State Examination(MMSE)were used to evaluate cognitive function,while the Hamilton Anxiety Scale(HAMA)and patient health questionnaire-9(PHQ-9)were used to assess anxiety and depression levels,and the mini nutritional assessment(MNA)was used to evaluate nutritional status.According to the MMSE scores,the elderly were divided into three groups:no cognitive impairment(MMSE≥27),mild cognitive impairment(MMSE 21-26),and moderate to severe cognitive impairment(MMSE≤20).The general data,lifestyle habits,and scale scores of the three groups were compared.Ordered logistic regression was used to analyze the influencing factors of sleep quality.Results There were statistically significant differences in age,gender,waist circumference,body mass index(BMI),education level,pet ownership,smoking,drinking,mahjong playing behavior,exercise habits,and scale scores among the three groups(P＜0.05).Logistic regression analysis showed that age,waist circumference,gender,drinking habits,mahjong playing behavior,and chronic comorbidities are influencing factors for the PSQI grading in the elderly(P＜0.05).The MMSE score(OR=1.037,P=0.001),SCD score(OR=1.123,P＜0.001),HAMA score(OR=1.183,P＜0.001),PHQ-9 score(OR=1.249,P＜0.001)are positive influencing factors for PSQI grading,while the MNA score is a negative influencing factor(OR=0.960,P=0.037).Conclusions Advanced age,female gender,low education level,no pet ownership,no mahjong playing behavior,no exercise habits,and poor sleep quality are risk factors for cognitive impairment in the elderly.Advanced age,female gender,no mahjong playing behavior and poor nutritional status are influencing factors for poor sleep quality in the elderly,and severe comorbidities,anxiety,depression,and subjective decline in cognitive function all affect sleep quality.

BACKGROUND:With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear.METHODS:This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA.RESULTS:S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA.CONCLUSION:S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.

ObjectiveTo explore the application value and related factors of serum carbonic anhydrase Ⅲ (CAⅢ) in the clinical diagnosis of mild to moderate Alzheimer disease (AD). MethodsA total of 106 elderly patients initially diagnosed with mild to moderate AD at Huashan Hospital, Fudan University from October 2020 to November 2022 were enrolled as the AD group, and 89 healthy elderly people during the same period were enrolled as the control group. The serum biochemical indicators including liver and kidney function, blood lipids, blood glucose, folic acid and homocysteine were detected in both groups. Cognitive function was assessed by Mini-mental State Examination (MMSE). Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to assess psychological status. The activities of daily living (ADL) were assessed by modified Barthel Index (BI). Serum CAⅢ levels were measured by enzyme-linked immunosorbent assay (ELISA). Correlation analysis and multivariate linear regression analysis were used to identify factors influencing serum CAⅢ levels, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of serum CAⅢ levels in elderly patients with mild to moderate AD. ResultsThe MMSE score of the AD group was significantly lower than that of the control group (P＜0.001), and the PHQ-9 and GAD-7 scores were significantly higher than those of the control group (P＜0.001). The serum CAⅢ level in the AD group was significantly lower than that in the control group (P＜0.000 1). In patients with AD, serum CAⅢ levels in patients with a disease course ＞3 years, accompanied by depression or anxiety, moderate AD, and serum creatinine≤111 μmol/L were significantly lower than those in patients with a disease course ≤3 years, normal emotions, mild AD, and serum creatinine ＞111 μmol/L (P＜0.05). Correlation analysis and multivariate linear regression analysis showed that serum CAⅢ levels were negatively correlated with disease duration, PHQ-9 score, GAD-7 scores and severity degree, positively correlated with serum creatinine level (P＜0.05). The PHQ-9 score, severity degree, and serum creatinine level were independent related factors for serum CAⅢ level in mild to moderate AD elderly patients (P＜0.05). ROC curve result showed that the area under the curve (AUC) of serum CAⅢ in diagnosing mild to moderate AD in elderly patients was 0.946, with sensitivity and specificity of 88.79% and 96.74%, respectively. ConclusionsSerum CAⅢ levels in elderly patients with mild to moderate AD are higher than those in healthy individuals. Mild AD, without depressive mood, and elevated serum creatinine levels are related factors for elevated serum CAⅢ levels in elderly AD patients. Serum CAⅢ may serve as a novel biological marker for the diagnosis of mild to moderate AD in the elderly.

The incidence of antibiotic-related diarrhea (AAD) is high in older adults. To examine the gut microbiota changes in older adults who received antibiotics to identify the microbial signatures associated with antibiotic use and AAD. A nested prospective observational cohort study was conducted between December 2019 and June 2021 in patients ≥ 65 years old at Huashan Hospital affiliated with Fudan University. The patients were grouped as antibiotic-treated (HA group) and no antibiotics (HC group); the HA group was subdivided as with vs. without AAD. Fecal samples were collected at admission (i.e., before eventual antibiotics) and after 7 days. Thirty-eight and 19 participants were included in the HA and HC groups. There were significant differences in gut microbiota between the HA after antibiotics vs. HC groups, with a higher Firmicutes/Bacteroidetes ratio. Before antibiotics in the HA group, the relative abundances of Akkermansia and Alistipes were lower in the AAD subgroup than the no-AAD subgroup, while the relative abundance of Actinomyces was higher. After antibiotics in the HA group, specific bacterial species were decreased in the AAD subgroup compared with the no-AAD subgroup. Among HA participants without probiotics, the abundance of Akkermansia in the patients without AAD was higher than in the patients with AAD at baseline (P = 0.007). Patients with or without AAD have different gut microbiota compositions before antibiotics. Antibiotics can lead to dysbiosis, with a decrease in beneficial bacteria and an increase in Enterococcus.

Ethnopharmacological relevance: Qilong Quyu (QLQY) is a Chinese traditional medicine that improves the outcome of ischemic stroke patients, as shown in clinical practice. However, the neuroprotective mechanism of QLQY is unclear.Aim of the study: The aim of our study was evaluate the neuroprotection of QLQY in the cerebral ischemia mice model, and to explore its mechanism from the analysis of proteomics.Materials and methods: QLQY, at doses of 10 and 30 g/kg, was administered intragastrically to mice at 0, 24, 48 and 72 h after middle cerebral artery occlusion (MCAO). Infarction volume, neuronal loss, neurobehavior among the sham, MCAO+vehicle, and MCAO+QLQY groups were compared. The underlying mechanism of QLQY was explored by proteomic analysis and validated by tests with a chemical inhibitor.Results: QLQY dose-dependently reduced cerebral infarction and alleviated the neurological deficits induced by MCAO. Neurons in the penumbra were protected from death by QLQY treatment. A proteomics analysis revealed that ferroptosis and the peroxisome proliferator-activated receptor-α (PPAR-ɑ) signaling pathway were modulated significantly after QLQY treatment. These findings were supported by the significant modulation of biomarkers of ferroptosis by QLQY, including reductions in malondialdehyde, free iron, and ferritin levels, and amelioration of decrements in both glutathione peroxidase (GPX) activity and the glutathione level caused by ischemia reperfusion. In MCAO mice treated with the PPAR-α inhibitor NXT629, the neuroprotection and alleviation of MCAO-induced ferroptosis obtained with QLQY were abolished.Conclusions: QLQY confers a neuroprotective effect against cerebral ischemia and ameliorates ischemic-stroke-induced-ferroptosis by activating the PPAR-α/GPX4 signaling pathway.

Background: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder leading to cognitive impairment in the elderly, and no effective treatment exists. Increasing evidence has demonstrated that physical therapy and electroacupuncture (EA) effectively improve spatial learning and memory abilities. Nevertheless, the mechanism underlying the effects of EA on AD pathology is largely unexplored. Acupuncture at Zusanli (ST 36) has previously been shown to improve cognitive impairment in AD, but the mechanism is unclear. According to recent studies, EA drives the vagal-adrenal axis from the hindlimb ST 36 acupoint but not from the abdominal Tianshu (ST 25) to curb severe inflammation in mice. This study examined whether ST 36 acupuncture improves cognitive dysfunction in AD model mice by improving neuroinflammation and its underlying mechanism.Methods: Male 5xFAD mice (aged 3, 6, and 9 months) were used as the AD animal model and were randomly divided into three groups: the AD model group (AD group), the electroacupuncture at ST 36 acupoint group (EA-ST 36 group), and the electroacupuncture at ST 25 acupoint group (EA-ST 25 group). Age-matched wild-type mice were used as the normal control (WT) group. EA (10 Hz, 0.5 mA) was applied to the acupoints on both sides for 15 min, 5 times per week for 4 weeks. Motor ability and cognitive ability were assessed by the open field test, the novel object recog-nition task, and the Morris water maze test. Thioflavin S staining and immunofluorescence were used to mark A & beta; plaques and microglia. The levels of NLRP3, caspase-1, ASC, interleukin (IL)-1 & beta;, and IL-18 in the hippocampus were assayed by Western blotting or qRT-PCR.Results: EA at ST 36, but not ST 25, significantly improved motor function and cognitive ability and reduced both A & beta; deposition and microglia and NLRP3 inflammasome activation in 5xFAD mice.Conclusion: EA stimulation at ST 36 effectively improved memory impairment in 5xFAD mice by a mechanism that regulated microglia activation and alleviated neuroinflammation by inhibiting the NLRP3 inflammatory response in the hippocampus. This study shows that ST 36 may be a specific acupoint to improve the condition of AD patients.

The disorders of glucolipid metabolism are prevalent in patients with type 2 diabetes mellitus (T2DM). Since the effects of Palmitic-Acid-Hydroxy-Stearic Acid (PAHSA) on T2DM were not fully understood, the study aimed to investigate the role of S-9- PAHSA in diabetes and the possible mechanisms. Male C57BL6 mice were fed with a high-fat diet (HFD) and injected with streptozotocin (STZ) to establish the diabetic mice model, and then administered with low- or high-dose S-9-PAHSA. Insulin, glycosylated serum protein (GSP), glucagon-like peptide-1 (GLP-1), and oxidized lowdensity lipoprotein (ox-LDL) were assessed by ELISA. SH-SY 5Y cells were incubated in a diabetic environment and treated with S-9-PAHSA, R-9-PAHSA, or 9-PAHSA. Cell viability, cell proliferation, apoptosis, lactate dehydrogenase (LDH), and reactive oxygen species (ROS) were measured by corresponding kits. Protein expressions were determined by western blot. The results showed high-does S-9-PAHSA improved insulin resistance and lowered ox-LDL. Compared with the control group, the significantly up-regulated expression of p62 and down-regulated expression of beclin 1 were found in diabetic mice and could be reversed by S-9-PAHSA. In vitro, S-9- PAHSA increased cell viability and proliferation while reducing LDH and ROS. S-9- PAHSA could reduce the expression of cleaved caspase-3 and TUNEL-positive cells, and increase the ratio of LC3II/I after high glucose and fatty acid stimulation in vitro. Downward trends were observed in PI3K and the phosphorylation of AKT in diabetic environments, which could be slightly restored by S-9-PAHSA. In conclusion, S-9- PAHSA could regulate glycolipid metabolism both in vivo and in vitro, indicating the vital role of S-9-PAHSA in T2DM.

Abstract Background: Apelin-12 has been proposed as a novel adipocytokine with vital roles in metabolic disorders. In this study, we aimed to explore the relationship between serum apelin-12 and metabolic inflammatory syndrome (MIS) in the elderly. Methods: The cross-sectional study involved 224 subjects aged over 60. According to their diagnoses of the four components of MIS (type 2 diabetes, non-alcoholic fatty liver disease, atherosclerosis, and obesity/overweight), they were divided into two groups: the control group (0 or 1 component n=63) and the MIS group (≥2 components, n=161). Serum levels of apelin-12, adiponectin and C-reactive protein were measured by ELISA. Results: Serum apelin-12 was significantly higher in the MIS group than in the control group (1.83 ng/mL (1.59-2.07) vs 1.66 ng/mL (1.45-1.92), P=0.001). Partial correlation analysis showed that apelin-12 levels were positively correlated with fasting insulin (ra=0.169), HOMA-IR (ra=0.183), ALT (ra=0.180), AST (ra=0.145) and CRP (ra=0.140, all Pa<0.05) and negatively associated with adiponectin (ra=-0.211) and HDL-C (ra=-0.156) after controlling age, sex and body mass index. Besides, after adjustment for age, sex, fasting blood glucose, diastolic blood pressure and total triglyceride, apelin-12 was still determined as an independent predictor for MIS. Conclusion: Serum apelin-12 can be an independent risk factor predicting metabolic inflammatory syndrome and may serve as a useful potential marker for the diagnosis of MIS in elderly Chinese.

目的 探讨老年认知障碍患者抑郁和焦虑评估的临床价值,分析老年认知功能减退的可能影响因素.方法 筛选2019年6月至2021年11月在复旦大学附属华山医院老年医学科门诊就诊的242例可疑认知障碍患者,按照认知水平,将其分为非认知障碍组(n=37)、轻度认知障碍(MCI)组(n=62)及痴呆组(n=143).通过简易精神状态检查量表(MMSE)及蒙特利尔认知评估量表(MoCA)完成认知水平测试,采用患者健康问卷抑郁症状群量表(PHQ-9)及广泛性焦虑量表(GAD-7)评估焦虑和抑郁状态;检测甲状腺功能、梅毒螺旋体和人免疫缺陷病毒血清标志物、血同型半胱氨酸(HCY)、叶酸、维生素B12、自身免疫性脑炎抗体及尿液阿尔茨海默相关神经丝蛋白(AD7c-NTP)水平.结果 认知障碍组、MCI组、痴呆组中抑郁患者分别有12例(32.4％)、30例(48.4％)和82例(57.3％),焦虑患者分别有10例(27.0％)、24例(38.7％)和72例(50.3％).MCI组和痴呆组中抑郁、焦虑者比例差异有统计学意义(P<0.05).3组人群之间甲状腺功能、自身免疫性脑炎抗体异常率差异无统计学意义.3组人群之间HCY、叶酸、AD7c-NTP异常率差异有统计学意义(P<0.05),维生素B12异常率差异无统计学意义.无序多分类logistic回归分析显示,以非认知障碍组为参照时,年龄和GAD-7评分增加为MCI发生的危险因素(P<0.05);年龄、HCY、PHQ-9和GAD-7评分增加为痴呆发生的危险因素(P<0.05);以MCI组为参照时,GAD-7评分增加为痴呆发生的危险因素(P<0.05).结论 老年认知障碍患者易伴抑郁、焦虑,患者认知功能与抑郁和焦虑状态、年龄,以及HCY、叶酸水平相关,建议门诊完善可疑老年认知障碍患者抑郁和焦虑评估.

Background: Alzheimer’s diseases (AD) is the most prevalent neurodegenerative disorder leading to cognitive impairment in the elderly and, to date, there is still no effective treatment. Increasing evidence has proved that a physical therapy, Electroacupuncture (EA), effectively improve spatial learning and memory abilities. Nevertheless, the mechanism underlying of EA effects, on AD pathology, are still largely unexplored. Acupuncture Zusanli (ST36) has previously been shown to improve cognitive impairment in AD, but the mechanism is unclear. According to recent studies, EA can drive vagal-adrenal axis from the hindlimb ST36 acupoint but not from the abdominal Tianshu (ST25) to curb severe inflammation in mice. The objective of this research is to determine whether ST36 acupuncture can improve cognitive dysfunction in AD model mice by improving neuroinflammation and its underlying mechanism.Methods: 3-, 6- and 9-month-old male 5xFAD mice were used as an AD animal model, and mice of each month were randomly divided in to three groups separately: AD model group (AD group), electroacupuncture at ST36 acupoint group (EA-ST36 group), electroacupuncture at ST25 acupoint group (EA-ST25 group). In the control group, age-matched wild-type mice were used as the normal control group (WT group). EA (10Hz, 0.5mA) was applied to acupoints on both sides for 15 min, 5 times per week for 4 weeks. The motor and cognitive ability were assessed by open field test (OFT), novel object recognition task (NORT) and Morris water maze (MWM) test. Thiofavin S staining and immunofluorescence was used to mark Aβ plaques and microglia. The expressions of NLRP3, Caspase-1, ASC and IL-1β in the hippocampus were observed by Western Blot or RT-qPCR.Results: EA at ST36 but not ST25 could significantly improve the motor function and cognitive ability, reduce Aβ deposition, reduce the activation of microglia and reduce the expression of NLRP3 inflammasome and IL-1β in 5×FAD mice.Conclusion: Electroacupuncture stimulation at ST36 instead ST25 acupoint effectively promotes the recovery of learning memory function in 5xFAD mice via a mechanism that regulate microglia activation and alleviate neuroinflammation by inhibition of NLRP3 inflammatory response in the hippocampus.Funding Information: This study was supported by Health and Family Planning Research Project of the Pudong New Area Health Committee (PW2020E-4); Medical Innovation Research Special Project of Science and Technology Innovation Action Plan for Shanghai 2021(21Y21920200) and the Siming Youth Foundation of Shuguang Hospital (SGKJ-202101).Conflict of Interests: Authors do not have any financial or nonfinancial competing interests with regard to the data presented in the manuscript.Ethical Approval: All experimental protocols were in strict accordance with the regulations of the National Institutes of Health guide for the care and use of laboratory animals, formulated by the Ministry of Science and Technology of the People's Republic of China and were approved by the Animals Research Ethics Committee of Shanghai University of Chinese Medicine (No.PZSHUTCM200821019).

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by severe pulmonary vascular wall remodeling and perivascular inflammation. Resolvin E1 (RvE1), a proresolving lipid mediator, has protective effects against various inflammatory diseases. However, the effect of RvE1 on PAH development remains to be determined. We aimed to investigate whether RvE1 has a therapeutic effect on PAH and, if so, to elucidate the molecular mechanisms underlying its effects. A hypoxia+SU5416-induced mouse model of pulmonary hypertension (PH) and an monocrotaline-induced rat model of PH were used to test therapeutic effect of RvE1. Lung tissues and plasma samples were collected from patients with PAH and rodent models to examine RvE1 production and its receptor chemerin chemokine-like receptor 1 (ChemR23) expression. We observed that RvE1 generation was reduced in the plasma of patients with idiopathic PAH and in lungs from experimental rodent models of PH. ChemR23 expression was markedly downregulated in hypoxia-exposed mouse pulmonary artery smooth muscle cells (PASMCs) and pulmonary arteries from PH rodents and patients with idiopathic PAH. RvE1 treatment alleviated experimental PH in both male and female rodents by inhibiting PASMC proliferation. Deletion of ChemR23 in vascular SMCs abolished the protective effect of RvE1 against hypoxia+SU5416-induced PAH in mice. Mechanistically, the RvE1/ChemR23 axis suppressed hypoxia-induced PASMC proliferation by inhibiting proliferative wingless-type MMTV integration site family member 7a/β-catenin signaling. Activation of ChemR23 by RvE1 diminished wingless-type MMTV integration site family member 7a expression in PASMCs by inhibiting protein kinase A-mediated Egr2 (early growth response 2) phosphorylation at Ser349. Thus, the RvE1/ChemR23 axis represses experimental PAH by modulating wingless-type MMTV integration site family member 7a/β-catenin signaling in PASMCs and may serve as a therapeutic target for the management of PAH.