Objective:To investigate the prevalence and mortality of dementia and assess the impact of geriatric syndromes (GS) on the risk for dementia and death in elderly population in Beijing.Methods:A cross-sectional survey was conducted in the elderly population aged ≥65 years and selected by a multi-stage sampling in Beijing during 2013-2015. Cognitive function was screened using the Chinese Revised Version of the Mini-Mental State Examination (MMSE). Then, neurological examination and psychiatric assessment were performed for those with the MMSE score lower than the cut-off value. The information about GS prevalence was also collected. The study also collected death records for all individuals from baseline until December 31, 2019. Based on the age and gender distribution from Beijing data of the 2010 Six th National Population Census, the dementia prevalence in the study population was directly standardized. Logistic regression analysis was used to evaluate the association of different forms of dementia with GS, and Cox proportional hazards regression model was used to estimate the hazard ratio ( HR) and 95% CI of death. Results:During 2013-2015, a total of 2 935 individuals completed dementia assessments, of which 167 were diagnosed with dementia. The standardized prevalence of dementia was 5.9% (95% CI: 5.0%-17.4%). The individuals with Alzheimer's disease (AD) and vascular dementia (VaD) accounted for 58.7% and 28.1% of total individuals with dementia, respectively. Aging, lower education level, urinary incontinence, and fall were risk factors for AD, while disability of activity of daily life dependence, hypertension, and stroke were found to be risk factors for VaD. After a median follow-up of 5.44 person-years, 399 deaths were recorded. The 5-year mortality risk was 2.87 (95% CI: 1.92-4.17) times and 4.93 (95% CI: 3.23-7.53) times higher for the elderly individuals with AD and VaD, respectively, compared to non-demented individuals. After adjusting for demographic, GS, and cardiovascular risk factors, the mortality risk in the elderly individuals with AD showed no significant difference compared with non-demented individuals ( HR=1.32, 95% CI: 0.89-1.97), while the mortality risk in those with VaD was 2.46 (95% CI: 1.49-4.05) times higher than that in non-demented individuals. Conclusions:The prevalence of dementia in Beijing increased significantly in the context of population aging, especially the prevalence of AD. The presence of GS increased the risks for AD and VaD, as well as the risk for death. Close attention needs to be paid to GS management in dementia prevention in elderly population.

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Objective:To explore the diagnostic value of the serial position effect combined with delayed recall of auditory verbal learning test in diagnosing the elderly patients with different levels of cognitive impairment.Methods:A total of 310 subjects were enrolled and divided into three groups: the normal control group(NC group, n=128), the mild cognitive impairment group(MCI group, n=133)and the mild Alzheimer's disease group(mild AD group, n=149)matched for gender, age and education level.Comprehensive neuro-psychological tests were performed on all subjects, and the Auditory Verbal Learning Test-Huashan version(AVLT-H)was used to analyze the serial position effect.Results:There were significant differences in the primacy effect of the second and third time of immediate recall, short-term and long-term delayed recall among the three groups( P<0.05), but no difference was found in the recency effect between the MCI and mild AD groups( P>0.05). The long-term delayed primacy effect combined with the short-term delayed recall showed a better validity to distinguish those elderly subjects with different levels of cognitive impairment than other memorial indexes, and the correlative sensitivity and specificity were 83.21% and 71.43%(NC group vs.MCI group), 85.71% and 92.86%(NC group vs.mild AD group), 66.67% and 75.57%(MCI group vs.mild AD group), respectively. Conclusions:The long-term delayed primacy effect combined with the short-term delayed recall can assist in distinguishing elderly patients with different levels of cognitive impairment.

Objective: To investigate the prevalence characters of peripheral artery disease (PAD) and associated factors among people aged 35 and above in Beijing. Methods: This was a cross-sectional study. A total of 5 208 community-based individuals aged equal and above 35 in Beijing were chosen with stratified multistage random sampling method. Structure questionnaire was used to collected the information of demographic factors, habits and chronic disease history. Ankle brachial blood pressure was detected and ankle brachial index (ABI) was calculated. ABI was used to diagnose PAD (ABI≤0.90). Based on the 2010 Beijing Municipal Population Census, the age-and gender-specific weight-adjusted sample was acquired to estimate the prevalence of PAD and corresponding 95% confidence intervals (CI). Multivariate logistic regression analysis was performed to estimate the associated factors of PAD. Results: The age-and sex-standardized prevalence of PAD was 3.84% (200/5 208, 95%CI 3.32%-4.36%). There was no significant difference between male and female (3.83%(102/2 664, 95%CI 3.10%-4.56%) vs. 3.85% (98/2 544, 95%CI 3.10%-4.60%), P=0.965). The prevalence of PAD in urban was higher than that in rural (4.34% (163/3 755, 95%CI 3.69%-4.99%) vs. 2.55% (37/1 453, 95%CI 1.74%-3.36%), P=0.001). Furthermore, the prevalence of PAD increased with age (P_trend<0.01), and the difference between genders did not change with ageing (all P>0.05). In addition, age (OR=1.03, 95%CI 1.01-1.04), urban (OR=1.52, 95%CI 1.08-2.12), smoking (OR=1.83, 95%CI 1.29-2.59), hypertension (OR=1.61, 95%CI 1.17-2.22) and diabetes (OR=1.44, 95%CI 1.08-1.93) were related with increased risk of PAD in logistic regression analysis models. Conclusions The prevalence of PAD increases with age in Beijing and there are significant difference between urban and rural on prevalence of PAD. Age, urban, smoking, hypertension and diabetes are related with increased risk of PAD.

Objective To investigate the prevalence characters of peripheral artery disease (PAD) and associated factors among people aged 35 and above in Beijing. Methods This was a cross?sectional study. A total of 5 208 community?based individuals aged equal and above 35 in Beijing were chosen with stratified multistage random sampling method. Structure questionnaire was used to collected the information of demographic factors, habits and chronic disease history. Ankle brachial blood pressure was detected and ankle brachial index (ABI) was calculated. ABI was used to diagnose PAD (ABI≤0.90). Based on the 2010 Beijing Municipal Population Census, the age?and gender?specific weight?adjusted sample was acquired to estimate the prevalence of PAD and corresponding 95% confidence intervals ( CI ). Multivariate logistic regression analysis was performed to estimate the associated factors of PAD. Results The age?and sex?standardized prevalence of PAD was 3.84% (200/5 208, 95%CI 3.32%-4.36%). There was no significant difference between male and female (3.83%(102/2 664 ,95%CI 3.10%-4.56%) vs. 3.85% (98/2 544,95% CI 3.10%-4.60%), P=0.965). The prevalence of PAD in urban was higher than that in rural (4.34% (163/3 755,95%CI 3.69%-4.99%) vs. 2.55% (37/1 453,95%CI 1.74%-3.36%), P=0.001). Furthermore, the prevalence of PAD increased with age (Ptrend<0.01), and the difference between genders did not change with ageing (all P>0.05). In addition, age (OR=1.03, 95%CI 1.01-1.04), urban (OR=1.52, 95%CI 1.08-2.12), smoking ( OR=1.83, 95%CI 1.29-2.59), hypertension ( OR=1.61, 95%CI 1.17-2.22) and diabetes (OR=1.44, 95%CI 1.08-1.93) were related with increased risk of PAD in logistic regression analysis models. Conclusions The prevalence of PAD increases with age in Beijing and there are significant difference between urban and rural on prevalence of PAD. Age, urban, smoking, hypertension and diabetes are related with increased risk of PAD.

[Abstract] Objective: To investigate the expression and clinical significance of PD-1/PD-L1 in gastric cancer (GC) tissues. Methods: Paraffin embedded tumor tissues and clinical data of 82 GC patients who had undergone operation at the Fourth Hospital of Hebei Medical University from January 2007 to December 2007 were collected, and their survival status was followed. The protein expressions of PD-1 and PD-L1 in tumor tissues were detected by immunohistochemistry. Kaplan-Meier analysis and Log-Rank test were adopted to analyze the survival of GC patients, and the ROC curve was plotted. Results: The positive rate of PD-L1 protein expression was 42.68% while the positive rate of PD-1 expression was 13.41% in GC tissues. The positive rate of PD-1 and PD-L1 expression in GC tissues of patients without pre-operative distant metastasis was significantly lower than those patients with pre-operative metastasis (PD1： 3.28% vs 42.86%; PD-L1： 13.11% vs 90.48%; all P<0.01). The positive rate of PD-L1 expression in tumor stroma of patients without pre-operative distant metastasis was significantly lower than those with metastasis (PD-L1: 13.11% v s 47.62%, P<0.01). The resection range of stomach, PD-L1 over-expression and the presence of pre-operative distant metastasis were the adverse factors affecting the prognosis of patients with GC (P<0.05). Conclusion: PD-1 and PD-L1 expressions in GC tissues were closely related to the presence of pre-operative distant metastasis and the depth of tumor infiltration. The postoperative survival of patients who were PD-L1 positive was shorter than the negative ones.

Objective To investigate the prevalence and risk factors of H-type hypertension among middle-aged and elderly people in Beijing community. Methods A cross-sectional study by recruiting 1 458 middle-aged and elderly people from a cohort of the "Beijing Longitudinal Study of Aging" in 2009 was conducted. All participants were asked to complete a standardized questionnaire, physical examination and laboratory examinations. Hyperhomocysteinemia was defined as homocysteine (Hcy) > 15 μmol/L, and H- type hypertension was defined as having hypertension and hyperhomocysteinemia simultaneously. The prevalence of H-type hypertension was estimated by using the results of 2000 Beijing population census to weight the data. Multivariate Logistic regression analysis was preformed to estimate the associated factors of H-type hypertension. Results The age was (69.48 ± 8.09) years, and the distribution of Hcy was skewed with the median of 16.56 μmol/L. After weight, the prevalence of hyperhomocysteinemia was 57.20% (834/1 458), and the prevalence of H-type hypertension was 35.32% (515/1 458), accounting for 59.47% (515/866) in patients with hypertension. The ageing, male, hyperuricemia, estimated glomerular filtration rate (eGFR) and insufficiency of fishes/ shrimps were independent risk factors of H-type hypertension ( OR = 2.30, 1.04, 1.02, 0.95 and 0.67; 95% CI 1.54-3.44, 1.02-1.06, 1.04-1.06, 0.94-0.97 and 0.46-0.97; P＜0.01 or＜0.05). Conclusions The proportion of H-type hypertension is high in the middle-aged and elderly people in Beijing community. Lowering uric acid, protection of renal function and intake sufficient fishes and shrimps might prevent and control H-type hypertension.

Objective To find out the prevalence of urinary incontinence(UI),as well as its impact on self assessed life quality in community dwelling elderly Beijing residents.Methods A total of 2 878 local elderly residents(≥ 65 years)were enrolled through stratified cluster random sampling from July 2013 to December 2014 in Beijing.A face-to-face questionnaire survey and physical examination were conducted by trained investigators.UI was screened using ICIQ SF.Prevalence of UI was adjusted by the standard population of Beijing and the number of elderly people with UI was estimated.Results The overall prevalence of UI was 24.6％.The morbidity of UI was 18.5％ in male and 29.8％ in female participants.The estimated number of elderly UI patients in Beijing was about 445 thousands,with 153 thousand male and 292 female patients.After adjustment for potential confounding demographic,lifestyle and chronic disease factors,logistic regression analysis revealed that UI was negatively correlated with several self-assessed measures,including quality of life,health,sleep quality,activities of daily life,sexual life and relationship with other people(all P＜0.05).Moreover,negative emotions in the last four weeks increased in the elderly with UI.Conclusions Nearly one quarter of the aged population,especially among aged women,in Beijing suffer from UI.UI severely affects the quality of life and emotions in aged persons.It is necessary to take early interventions to improve quality of life and promote healthy aging.

Although most microbes are not readily cultured in the lab, microbial DNA can be extracted directly from an environmental sample and be functionally expressed in a suitable host for natural products discovery, and this approach has been termed "metagenomics". An E'mei Mountain soil metagenomic library was constructed using an Escherichia coli-Streptomyces shuttle vector for functional based screening of anti-bacterial clones in Streptomyces albus host. Two active clones were obtained and their fermentation broths were studied for the inhibitory effect on Staphylococcus aureus biofilm. Their fermentation products have a good inhibitory effect on the formation of S. aureus biofilm, and the inhibitory effect could exceed 90% when the concentration of sample was 2 MIC (Minimum Inhibitory Concentration). In addition, two samples had significantly effect on S. aureus biofilm dispersal, and the clearance rate of EM110 was higher than EM123. In conclusion, substances with strong bioactivities on biofilm formation and dispersal of S. aureus could be discovered by using metagenomics technology.