Associations of perceived stress with loneliness and depressive symptoms: the mediating role of sleep quality.

BACKGROUND: Whether perceived stress is associated with loneliness and depressive symptoms in general adults, and to what extent sleep quality mediates the associations, remains unknown. The aim of this study was to estimate the associations of perceived stress with loneliness and depressive symptoms, and the mediating role of sleep quality in these associations. METHODS: Cross-sectional data on 734 participants (aged 18-87 years) were analyzed. Perceived stress was assessed using the 10-item Perceived Stress Scale (PSS-10; range 0-40). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI; range 0-21). Loneliness was assessed using the three-item short form of the Revised University of California, Los Angeles (UCLA) loneliness scale (range 3-9). Depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression (CESD-10) Scale (range 0-30). General linear regression models, multivariable logistic regression models, and formal mediation analysis were performed. RESULTS: After adjustment for age and sex, we found that with each 1-point increment in the perceived stress score, both the loneliness score (ß = 0.07; 95% confidence interval [CI]: 0.06, 0.08) and depression score (ß = 0.45; 95% CI: 0.40, 0.49) increased significantly. Robust results were observed when adjusting for more confounders. Furthermore, sleep quality mediated 5.3% (95% CI: 1.3%, 10.0%; P = 0.014) and 9.7% (95% CI: 6.2%, 14.0%; P < 0.001) of the associations of perceived stress score with loneliness score and depression score, respectively. CONCLUSIONS: In general Chinese adults, perceived stress was positively associated with loneliness and depressive symptoms, and sleep quality partially mediated these associations. The findings reveal a potential pathway from perceived stress to mental health through sleep behaviors, and highlight the importance of implementing sleep intervention programs for promoting mental health among those who feel highly stressed.

Influencing Factors of Healthy Aging Risk Assessed Using Biomarkers: A Life Course Perspective.

Assessing individual risks of healthy aging using biomarkers and identifying associated factors have become important areas of research. In this study, we conducted a literature review of relevant publications between 2018 and 2023 in both Chinese and English databases. Previous studies have predominantly used single biomarkers, such as C-reactive protein, or focused on specific life course stages and factors such as socioeconomic status, mental health, educational levels, and unhealthy lifestyles. By summarizing the progress in this field, our study provides valuable insights and future directions for promoting healthy aging from a life course perspective.

Transition to healthier lifestyle associated with reduced risk of incident dementia and decreased hippocampal atrophy.

BACKGROUND: Research has estimated the associations of lifestyle at one-time point with the risk of dementia and hippocampal volume, but the impact of lifestyle transition on dementia and hippocampal volume remains unclear. This study aims to examine the associations of lifestyle transition with the risk of dementia and hippocampal volume. METHODS: Based on data from the UK Biobank, a weighted lifestyle score was constructed by incorporating six lifestyle factors. Within each baseline lifestyle group (i.e., healthy, intermediate, and unhealthy), lifestyle transition was classified into decline, maintenance, and improvement. Cox proportional hazard regression was used to estimate the association of lifestyle transition and incident dementia (N = 16,305). A multiple linear regression model was used to estimate the association between lifestyle transition and hippocampal volume (N = 5849). RESULTS: During a median follow-up period of 8.6 years, 120 (0.7 %) dementia events were documented. Among participants with healthy baseline lifestyles, the improvement group had a lower risk of incident dementia (HR: 0.18, 95 % CI: 0.04-0.81) and a larger hippocampal volume (ß = 111.69, P = 0.026) than the decline group. Similar results were observed among participants with intermediate baseline lifestyles regarding dementia risk but not hippocampal volume. No benefits were observed in the improvement group among those with unhealthy baseline lifestyles. LIMITATIONS: A lower incidence of dementia than other cohort study and this may have resulted in an underestimation of the risk of dementia. CONCLUSIONS: Earlier transitions to healthier lifestyle were associated with reduced risk of incident dementia and decreased hippocampal atrophy.

Corydalis tomentella Franch. Exerts anti-inflammatory and analgesic effects by regulating the calcium signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis tomentella Franch. is a perennial cespitose plant commonly used to treat stomachaches as a folk medicine. The C. tomentella total alkaloids have good protective effects against acute liver injury and potential anti-hepatoma and anti-Alzheimer's disease activities. AIM OF THE STUDY: To establish an effective purification process for total alkaloids from C. tomentella and investigate the mechanism of their anti-inflammatory effects. MATERIALS AND METHODS: Corydalis tomentella were purified using macroporous resin. Then the crude and purified C. tomentella extracts (cCTE and pCTE) were qualitatively analyzed using UPLC-Triple-TOF-MS/MS. The cCTE and pCTE were used to investigate and compare their anti-inflammatory effects on lipopolysaccharide (LPS)-induced RAW264.7 cells. Doses at 100, 200 and 400 mg/kg/d of pCTE were used to study their anti-inflammatory and analgesic activities in mice with xylene-induced ear swelling and acetic acid-induced writhing tests. Content of nitric oxide (NO), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) were determined both in RAW264.7 cells and mice. Network pharmacology was used to predict the anti-inflammatory mechanism of C. tomentella, and the key enzymes were validated using qPCR and Western Blot analysis. Concentration of intracellular Ca2+ was detected using flow cytometric analysis. RESULTS: The C. tomentella total alkaloid purity increased from 6.29% to 47.34% under optimal purification conditions. A total of 54 alkaloids were identified from CTE. Both cCTE and pCTE could suppress the LPS-induced production of NO, IL-6, IL-1ß, and TNF-α in RAW264.7 cells. The pCTE exhibited a more potent anti-inflammatory effect; it also inhibited pain induced by xylene and acetic acid in mice. The calcium signaling pathway is associated with the anti-inflammatory and analgesic activities of C. tomentella. The mRNA expression of nitric oxide synthase (NOS) 2, NOS3 and calmodulin1 (CALM1) was regulated by C. tomentella through the reduction of inflammation-induced Ca2+ influx, and it also exhibited a more pronounced effect than the positive control (L-NG-nitro arginine methyl ester). CONCLUSIONS: Purified C. tomentella extract shows anti-inflammatory effect both in vitro and in vivo. It exerts anti-inflammatory and analgesic effects through the calcium signaling pathway by down-regulating NOS2 and CALM1 expression and up-regulating NOS3 expression in LPS-induced RAW264.7 cells, and decreasing intracellular Ca2+ concentration.

Sociodemographic Factors Predict Incident Mild Cognitive Impairment: A Brief Review and Empirical Study.

OBJECTIVES: Mild cognitive impairment (MCI) is a transitional stage between normal cognitive aging and dementia that increases the risk of progressive cognitive decline. Early prediction of MCI could be beneficial for identifying vulnerable individuals in the community and planning primary and secondary prevention to reduce the incidence of MCI. DESIGN: A narrative review and cohort study. SETTING AND PARTICIPANTS: We review the MCI prediction based on the assessment of sociodemographic factors. We included participants from 3 surveys: 8915 from wave 2011/2012 of the China Health and Retirement Longitudinal Study (CHARLS), 9765 from the 2011 Chinese Longitudinal Healthy Longevity Survey (CLHLS), and 1823 from the 2014 Rugao Longevity and Ageing Study (RuLAS). METHODS: We searched in PubMed, Embase, and Web of Science Core Collection between January 1, 2019, and December 30, 2022. To construct the composite risk score, a multivariate Cox proportional hazards regression model was used. The performance of the score was assessed using receiver operating characteristic (ROC) curves. Furthermore, the composite risk score was validated in 2 longitudinal cohorts, CLHLS and RuLAS. RESULTS: We concluded on 20 articles from 892 available. The results suggested that the previous models suffered from several defects, including overreliance on cross-sectional data, low predictive utility, inconvenient measurement, and inapplicability to developing countries. Our empirical work suggested that the area under the curve for a 5-year MCI prediction was 0.861 in CHARLS, 0.797 in CLHLS, and 0.823 in RuLAS. We designed a publicly available online tool for this composite risk score. CONCLUSIONS AND IMPLICATIONS: Attention to these sociodemographic factors related to the incidence of MCI can be beneficially incorporated into the current work, which will set the stage for better early prediction of MCI before its incidence and for reducing the burden of the disease.

miR-216b-5p mediates autophagy to reverses cisplatin resistance of esophageal cancer Eca109 cells by targeting ATG5 / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨miR-216b-5p对食管癌Eca109细胞顺铂（DDP）耐药性的影响及其作用机制。方法:采用qPCR法检测miR-216b-5p在食管癌细胞TE-1、KYSE-150、Eca109和耐药细胞Eca109/DDP中的表达水平。利用脂质体转染技术分别将miR-216b-5p mimic及mimic NC、自噬相关蛋白5（ATG5）过表达质粒转染到Eca109/DDP细胞中，用CCK-8、EdU法和FCM分别检测转染后细胞的增殖和凋亡；mRFP-eGFP-LC3双荧光标记实验检测mRFP-eGFP-LC3慢病毒感染后各组细胞自噬发生情况，WB法检测自噬相关蛋白LC3、Beclin 1和P62表达。用荧光素酶报告基因实验验证miR-216b-5p与ATG5的靶向关系，WB法检测ATG5的表达。建立裸鼠Eca109/DDP细胞移植瘤模型，观察miR-216b-5p过表达对移植瘤生长的影响。结果：miR-216b-5p在TE-1、KYSE-150、Eca109和Eca109/DDP细胞中均呈低表达（均P<0.05）。过表达miR-216b-5p可显著抑制Eca109/DDP细胞的增殖并诱导凋亡（均P<0.05），减少细胞中自噬小体数量（P<0.05），下调LC3Ⅱ/LC3Ⅰ比值和Beclin 1蛋白水平、上调P62蛋白水平（均P<0.05）。双荧光素酶报告基因实验证实miR-216b-5p靶向并负调控ATG5的表达（P<0.05），过表达ATG5可使miR-216b-5p mimic对Eca109/DDP细胞增殖、自噬的抑制作用和凋亡的诱导作用明显减弱（均P<0.05），自噬相关蛋白P62表达降低、LC3Ⅱ/LC3Ⅰ比值和Beclin 1表达升高（均P<0.05）。荷瘤实验结果表明，miR-216b-5p过表达可显著抑制裸鼠移植瘤的生长（P<0.05）。结论：miR-216b-5p过表达可逆转食管癌Eca109/DDP细胞对DDP的耐药性，其机制可能与靶向负调控ATG5表达并影响细胞自噬有关。

Catastrophic health expenditure among Chinese adults living alone with cognitive impairment: findings from the CHARLS.

BACKGROUND: The catastrophic health expenditure of older adults results in serious consequences; however, the issue of whether cognitive status and living situations contribute to such financial burdens is uncertain. Our aim was to compare the differences in catastrophic health expenditure between adults living alone with cognitive impairment and those adults living with others and with normal cognition. METHODS: We identified 909 observations of participants living alone with cognitive impairment (cases) and 37,432 observations of participants living with others and with normal cognition (comparators) from the 2011/2012, 2013, 2015 and 2018 waves of the China Health and Retirement Longitudinal Study (CHARLS). We used propensity score matching (1:2) to create matched cases and comparators in a covariate-adjusted logistic regression analysis. Catastrophic health expenditure was defined as an out-of-pocket cost for health care ≥40% of a household's capacity to pay. RESULTS: In comparison with participants living with others and with normal cognition, those adults living alone with cognitive impairment reported a higher percentage of catastrophic health expenditure (19.5% vs. 11.8%, respectively, P < 0.001). When controlling for age, sex, education, marital status, residence areas, alcohol consumption, smoking status and disease counts, we found that this subpopulation had significantly higher odds of having catastrophic health expenditure (odds ratio [OR] = 1.89, 95% confidence interval [CI]: 1.40, 2.56). Additional analyses confirmed the robustness of the results. CONCLUSIONS: This study demonstrated that adults living alone with cognitive impairment in the CHARLS experienced a high burden of catastrophic health expenditure. Health care policies on social health insurance and medical assistance should consider these vulnerable adults.

Association of lifestyle with mortality and the mediating role of aging among older adults in China.

OBJECTIVES: 1) examine the association between lifestyle and mortality; 2) examine the association between two aging measures and mortality; 3) evaluate the mediating effect of the two aging measures on the association between lifestyle and mortality among older Chinese adults. METHODS: We used data from 2039 older adults (≥ 65 years) from the 2011/2012 biomarker substudy of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). We created a healthy lifestyle index based on 5 factors (exercise, smoking, drinking, diet, and BMI, range: 0-5). We calculated two aging measures, the Klemera and Doubal method-biological age (KDM-BA) and physiological dysregulation (PD), based on 10 blood-based biomarkers using algorithms developed previously. A Cox proportional hazards model, general linear regression model, and formal mediation analysis were performed. RESULTS: After adjustment for age and sex, compared to participants without any healthy lifestyle factors, those with 5 healthy lifestyle factors had an 85% lower risk of mortality (hazard ratio [HR] = 0.15, 95% confidence interval [CI]: 0.04, 0.60). PD, but not KDM-BA, was significantly associated with mortality (HR = 1.69, 95% CI: 1.25, 2.29). The healthy lifestyle index was negatively associated with PD (ß = -0.021, P = 0.012). PD mediated 9% (95% CI: 1%, 52%, P = 0.043) of the total effect of the healthy lifestyle index on mortality. CONCLUSIONS: In the older Chinese population, healthy lifestyle reduces mortality risk and aging partially mediates this association. The findings highlight the importance of adherence to a healthy lifestyle for promoting phenotypic aging even in late life.

Kinetics of color development, pH decreasing, and anti-oxidative activity reduction of Maillard reaction in galactose/glycine model systems.

Galactose/glycine model systems of sugar concentration 0.035, 0.069, 0.139, and 0.278M were incubated at 60, 75, and 90°C separately for studying the reaction kinetics of color development, pH change, and system anti-oxidative activity change in Maillard reaction. The results indicated that system color development followed first-ordered kinetics on galactose concentration; system pH went linearly down with a logarithm-ordered kinetics on galactose concentration; and anti-oxidative activity reduced linearly with a first-ordered kinetics on galactose concentration. The values of Q10 and activation energy ranged from 1.98 to 2.00 and from 68.8 to 69.5kJ/mol, respectively, for these three properties.

[Expression of HIF-1alpha induced by ginkgolides in primary cultured cortical neurons and the relationship with ERK signal pathway].

AIM: To study the effects of ginkgolides (Gin) on the expression of hypoxia-inducible factor-1alpha (H1F-1alpha) in primary cultured cortical neurons treated with CoCl2 and the relationship with ERK signal pathway. METHODS: We observed the effects of Gin (37.5 mg/L) on morphology and viability on primary cultured cortical neurons with treatment of CoCl2 (125 micromol/L). The expression of HIF-1alpha and p-ERK of neurons induced by CoCl2 pretreated with Gin were assessed by Western-blot. We analyzed the relationship between HIF-1alpha expression activated by Gin and ERK signal pathway with treatment of PD98059 (100 micromol/L), a selective inhibitor of ERK. RESULTS: It was shown that Gin had protective effects on CoCl2 damaged neurons by raising the neuronal viability. Some basic expression of HIF-1alpha and p-ERK were observed in normal cultured cortical neurons. The expression of HIF-1alpha and p-ERK increased strikingly when treated with CoCl2 for 4 h. The levels of HIF-1alpha and p-ERK increased even more in the neurons pretreated with Gin for 24 h before CoCl2. The levels of HIF-1alpha and p-ERK were notably inhibited with pretreatment of PD98059, while Gin could prevent this inhibition. CONCLUSION: Gin has protective effects on neurons damaged by CoCl2 which might be related to the increase of the level of HIF-1alpha and the activation of ERK signal pathway.

[Prevention of Rhodiola-astragalus membranaceus compounds against simulated plateau hypoxia brain injury in rat].

OBJECTIVE: To observe the protective effects of Rhodiola-astragalus membranaceus mixture against brain damage during hypoxia under simulated plateau environment and the mechanisms maybe involved in. METHOD: Adult SD rats were randomly divided into 3 groups, which were normoxic control, simulated plateau hypoxia, and Rhodiola-astragalus membranaceus mixture pretreatment group. Rats in the latter two groups were exposed to simulated 8000 m altitude in a hypobaric chamber for 7 h. Water content, Na+, K(+)-ATPase activity and SOD activity in cerebral tissue, malondialdehyde (MDA) and lactic acid content in cerebral homogenate and serum were measured. RESULT: As compared with control group, cerebral water content was significantly higher in hypoxia group, while it was obviously lower in pretreatment group. MDA contents of hypoxia group both in cerebral homogenate and serum were higher than that of control group, while the pretreatment group they were both decreased obviously. Lactic acid content of hypoxia group in cerebral and in serum increased markedly and decreased drastically in pretreatment group compared to that of hypoxic group. CONCLUSION: Rhodiola-astragalus membranaceus mixture has preventive effects on hypoxic damage induced by simulated plateau environment. This prevention may be related to the antagonistic effect on membrane lipid peroxidation and the inhibition on the accumulation of lactic acid in brain tissue and serum.

[Effect of ginkgolides on gene expression of HIF-1alpha in primary cultured neurons].

AIM: To study the effects of ginkgolides (Gin) on the expression of hypoxia inducible factor-1 (HIF-1alpha) in hypoxic/ischemic neurons. METHODS: The gene expression of HIF-1alpha pretreated with or without Gin (37.5 microg/ml) was observed by RT-PCR on primary cultured cortical neurons in the condition of hypoxia and oxygen-glucose deprivation. RESULTS: Some basic expression of HIF-1alpha mRNA were observed in cultured cortical neurons. The expression of HIF-1alpha mRNA increased after 24 h treatment with Gin. The level of HIF-la mRNA increased also after 1 h hypoxia and further enhanced after the pretreatment with Gin. The expression of HIF-1alpha mRNA decreased with the deprivation of both oxygen and glucose, which reversed after the pretreatment of Gin. CONCLUSION: Gin could increase the expression of HIF-1alpha mRNA in hypoxic/ischemic cortical neurons.

[Effect of Safflor yellow against neonatal hypoxia on expression of NOSs mRNA].

AIM: To investigate the effect of Safflor yellow on the gene expression of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in neonatal asphyxia. METHODS: 30 minutes after SY 7 g/kg weight intraperitoneally was administered on the neonatal rats. After asphyxia for 40 minutes,the neonatal rats were reoxygenated for 48 h, and the nitric oxide synthases (NOSs) mRNA expression was assessed by semi-quantitative reverse transcription-polymerase chain reaction. RESULTS: Neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were up in hypoxia/reoxygenation (H/R) 48 h group, while both of them were down significantly in SY group, but no change was observed on endothelial nitric oxide synthase (eNOS). CONCLUSION: The protective of SY from brain damage induced by neonatal asphyxia might be associated with expression of NOSs mRNA.