Objective: To investigate the current status and influencing factors for cognitive frailty among the elderly in community, so as to provide the evidence for early identification and prevention of cognitive frailty among the elderly. Methods: Residents aged 60 years and above with local household registration from 11 counties (cities, districts) in Zhejiang Province from 2021 to 2023 were selected as study participants using a multistage random sampling method. Demographic information, lifestyle, and health status were collected through questionnaire surveys. Depressive symptoms were assessed using the Patient Health Questionnaire. Cognitive frailty was evaluated using the FRAIL Scale and the Mini-Mental State Examination. Factors affecting cognitive frailty among the elderly in community were identified using a multivariable logistic regression model. Results: A total of 16 613 individuals were surveyed, including 7 465 males (44.93%) and 9 148 females (55.07%). The average age was (70.97±7.29) years. A total of 784 individuals were detected with depressive symptoms, with a detection rate of 4.72%. A total of 724 individuals were detected with cognitive frailty, with a detection rate of 4.36%. Multivariable logistic regression analysis showed that females (OR=1.419, 95%CI: 1.179-1.708), aged ≥70 years (70-<80 years old, OR=1.869, 95%CI: 1.490-2.345; ≥80 years old, OR=5.017, 95%CI: 3.935-6.398), without a spouse (OR=1.495, 95%CI: 1.234-1.810), sedentary (OR=2.420, 95%CI: 1.829-3.202), chronic diseases (1 type, OR=1.456, 95%CI: 1.175-1.804; ≥2 types, OR=1.639, 95%CI: 1.314-2.045), and depressive symptoms (OR=4.191, 95%CI: 3.361-5.225) were associated with a higher risk of cognitive frailty among the elderly in community. Conversely, a lower risk of cognitive frailty was seen among the elderly in community who had primary school or above (primary school, OR=0.512, 95%CI: 0.389-0.676; junior high school or above, OR=0.464, 95%CI: 0.354-0.608), engaged in physical exercise (OR=0.396, 95%CI: 0.291-0.539), and were reported average or good self-rated health status (average, OR=0.641, 95%CI: 0.475-0.866; good, OR=0.150, 95%CI: 0.109-0.208). Conclusions The detection rate of cognitive frailty among the elderly in community is relatively low and is influenced by demographic factors such as gender, age, education level, as well as lifestyle like sedentary and physical exercise, and health status. It is recommended to reduce the risk of cognitive frailty among the elderly through multidimensional interventions, including health education, promotion of healthy lifestyles, and enhanced mental health support.

Objective: To establish a nomogram prediction model for Alzheimer's disease (AD) among the elderly in community, so as to provide the evidence for early screening and prevention of AD. Methods: Based on the Zhejiang Healthy Aging Cohort Study, the elderly aged 60-90 years who completed the baseline survey were selected as the study subjects. Follow-up surveys were conducted from 2015 to 2016 and from 2019 to 2021. Sociodemographic characteristics, lifestyle factors, medical history, and waist circumference were collected through questionnaire surveys and physical examinations. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), and a diagnosis of AD was made based on the Alzheimer's Disease Assessment Scale-Cognitive Subscale and medical history. The participants were randomly divided into training and validation sets at 8∶2 ratio. LASSO regression was used to screen for predictive factors. Multivariable logistic regression model was used to analyze predictive factors and construct a nomogram. The model was analyzed and evaluated using the receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 6 988 elderly were included at baseline, with a mean age of (68.19±6.63) years. There were 3 438 males (49.20%), and 3 550 females (50.80%). The median follow-up duration was 4.90 (interquartile range, 3.80) years, with 817 new cases of AD were identified, yielding an incidence of 11.69%. LASSO regression and multivariable logistic regression showed that age (OR=1.017, 95%CI: 1.005-1.030), gender (female, OR=1.820, 95%CI: 1.533-2.165), educational level (primary school, OR=0.813, 95%CI: 0.673-0.980), physical exercise (not active, OR=1.572, 95%CI: 1.260-1.980), dining companions (spouse and children, OR=0.771, 95%CI: 0.598-0.995), baseline MMSE score (OR=0.843, 95%CI: 0.821-0.866), and waist circumference (OR=0.981, 95%CI: 0.973-0.989) were risk predictors for AD among the elderly in community. The prediction model demonstrated an area under the ROC curve of 0.740 (95%CI: 0.698-0.783) in the validation set, with a sensitivity of 0.731 and a specificity of 0.667. DCA indicated that when the probability threshold was 0.060 to 0.325, the clinical net benefit was relatively high. Conclusion The AD risk prediction model constructed in this study has good discrimination and clinical practicability, can be used for early screening of AD among the elderly in the community.

BACKGROUND: Alpha-glucosidase inhibitors or dipeptidyl peptidase-4 inhibitors are both hypoglycemia agents that specifically impact on postprandial hyperglycemia. We compared the effects of acarbose and sitagliptin add on to metformin on time in range (TIR) and glycemic variability (GV) in Chinese patients with type 2 diabetes mellitus through continuous glucose monitoring (CGM). METHODS: This study was a randomized, open-label, active-con-trolled, parallel-group trial conducted at 15 centers in China from January 2020 to August 2022. We recruited patients with type 2 diabetes aged 18-65 years with body mass index (BMI) within 19-40 kg/m 2 and hemoglobin A1c (HbA1c) between 6.5% and 9.0%. Eligible patients were randomized to receive either metformin combined with acarbose 100 mg three times daily or metformin combined with sitagliptin 100 mg once daily for 28 days. After the first 14-day treatment period, patients wore CGM and entered another 14-day treatment period. The primary outcome was the level of TIR after treatment between groups. We also performed time series decomposition, dimensionality reduction, and clustering using the CGM data. RESULTS: A total of 701 participants received either acarbose or sitagliptin treatment in combination with metformin. There was no statistically significant difference in TIR between the two groups. Time below range (TBR) and coefficient of variation (CV) levels in acarbose users were significantly lower than those in sitagliptin users. Median (25th percentile, 75th percentile) of TBR below target level <3.9 mmol/L (TBR 3.9 ): Acarbose: 0.45% (0, 2.13%) vs . Sitagliptin: 0.78% (0, 3.12%), P = 0.042; Median (25th percentile, 75th percentile) of TBR below target level <3.0 mmol/L (TBR 3.0 ): Acarbose: 0 (0, 0.22%) vs . Sitagliptin: 0 (0, 0.63%), P = 0.033; CV: Acarbose: 22.44 ± 5.08% vs . Sitagliptin: 23.96 ± 5.19%, P <0.001. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV (group with small wave, moderate wave and big wave). No significant difference was found in the complexity of glucose time series index (CGI) between acarbose users and sitagliptin users. By using time series analysis and clustering, we distinguished three groups of patients with representative metabolism characteristics, especially in GV. CONCLUSIONS: Acarbose had slight advantages over sitagliptin in improving GV and reducing the risk of hypoglycemia. Time series analysis of CGM data may predict GV and the risk of hypoglycemia. TRIAL REGISTRATION Chinese Clinical Trial Registry: ChiCTR2000039424.
Humans ; Metformin/therapeutic use* ; Sitagliptin Phosphate/therapeutic use* ; Acarbose/therapeutic use* ; Diabetes Mellitus, Type 2/blood* ; Middle Aged ; Male ; Female ; Adult ; Blood Glucose/drug effects* ; Hypoglycemic Agents/therapeutic use* ; Aged ; Glycated Hemoglobin/metabolism* ; Adolescent ; Young Adult ; China ; East Asian People

Long non-coding RNAs(lncRNAs)play an indispensable role in the occurrence and development of ovarian cancer(OC).However,the potential involvement of lncRNAs in the progression of OC is largely unknown.To investigate the detailed roles and mechanisms of RAD51 homolog B-antisense 1(RAD51B-AS1),a novel lncRNA in OC,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was performed to verify the expression of RAD51B-AS1.Cellular proliferation,metastasis,and apoptosis were detected using the cell counting kit-8(CCK-8),colony-formation,transwell,and flow cytometry assays.Mouse xenograft models were established for the detection of tumorigenesis.The results revealed that RAD51B-AS1 was significantly upregulated in a highly metastatic human OC cell line and OC tissues.RAD51B-AS1 significantly increased the proliferation and metastasis of OC cells and enhanced their resistance to anoikis.Biogenetics prediction analysis revealed that the only target gene of RAD51B-AS1 was RAD51B.Subsequent gene function experiments revealed that RAD51B exerts the same biological effects as RAD51B-AS1.Rescue experiments demonstrated that the malignant biological behaviors promoted by RAD51B-AS1 overexpression were partially or completely reversed by RAD51B silencing in vitro and in vivo.Thus,RAD51B-AS1 promotes the malignant biological behaviors of OC and activates the protein kinase B(Akt)/B cell lymphoma protein-2(Bcl-2)signaling pathway,and these effects may be associated with the positive regulation of RAD51B expression.RAD51B-AS1 is expected to serve as a novel molecular biomarker for the diagnosis and prediction of poor prognosis in OC,and as a potential therapeutic target for disease management.

Objective:The present study used single-cell RNA sequencing(scRNA-seq)to characterize the cellular composition of ovarian carcinosarcoma(OCS)and identify its molecular characteristics.Methods:scRNA-seq was performed in resected primary OCS for an in-depth analysis of tumor cells and the tumor microenvironment.Immunohistochemistry staining was used for validation.The scRNA-seq data of OCS were compared with those of high-grade serous ovarian carcinoma(HGSOC)tumors and other OCS tumors.Results:Both malignant epithelial and malignant mesenchymal cells were observed in the OCS patient of this study.We identified four epithelial cell subclusters with different biological roles.Among them,epithelial subcluster 4 presented high levels of breast cancer type 1 susceptibility protein homolog(BRCA1)and DNA topoisomerase 2-α(TOP2A)expression and was related to drug resistance and cell cycle.We analyzed the interaction between epithelial and mesenchymal cells and found that fibroblast growth factor(FGF)and pleiotrophin(PTN)signalings were the main pathways contributing to communication between these cells.Moreover,we compared the malignant epithelial and mesenchymal cells of this OCS tumor with our previous published HGSOC scRNA-seq data and OCS data.All the epithelial subclusters in the OCS tumor could be found in the HGSOC samples.Notably,the mesenchymal subcluster C14 exhibited specific expression patterns in the OCS tumor,characterized by elevated expression of cytochrome P450 family 24 subfamily A member 1(CYP24A1),collagen type XXIII α1 chain(COL23A1),cholecystokinin(CCK),bone morphogenetic protein 7(BMP7),PTN,Wnt inhibitory factor 1(WIF1),and insulin-like growth factor 2(IGF2).Moreover,this subcluster showed distinct characteristics when compared with both another previously published OCS tumor and normal ovarian tissue.Conclusions:This study provides the single-cell transcriptomics signature of human OCS,which constitutes a new resource for elucidating OCS diversity.

Background: Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now. Methods This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.

Background: Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now. Methods This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.

Background: Epithelial ovarian cancer is the leading cause of death among gynecological malignancies. Platinum resistance remains a dilemma and bottleneck in treatment, and salvage chemotherapy has limited effectiveness. Recently, the role of secondary cytoreductive surgery (SCS) in patients with platinum-resistant recurrent ovarian cancer (ROC) has caused attention especially in patients with oligometastases. However, there is neither high-quality evidence-based evidence nor standardized criteria for selecting SCS for patients with platinum-resistant ROC until now. Methods This multicenter, randomized, controlled clinical trial is to evaluate the value of SCS and to clarify reliable criteria of utilizing SCS in women with ROC, which is led by Gynecologic Oncology Group, Women’s Hospital, Zhejiang University School of Medicine.Recruitment has started on January 1st, 2023, and is scheduled to end in December 2026.One hundred and forty participants with platinum-resistant ROC who meet the “RSCS criteria” will be randomized assigned at a ratio of 1:1 to either the experimental arm or the standard arm. Patients in the experimental arm will receive SCS followed by non-platinum single agent chemotherapy (paclitaxel, gemcitabine or liposomal adriamycin) for at least 4 cycles while patients in the standard arm will be provided with only non-platinum single agent chemotherapy. The primary outcome is progression-free survival. The secondary outcomes are overall survival, adverse events and health-related cancer-specific quality of life.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Objective:To investigate the inhibitory effect of combined strategy of poly adenosine diphosphate ribose polymerase (PARP) inhibitor and interleukin-1β (IL-1β) inhibitor on homologous recombination deficiency (HRD)-proficient ovarian cancer cells.Methods:(1) HRD-proficient ovarian cancer cell lines OVCAR3 and CAOV3 were treated with PARP inhibitor olaparib. Screening by RNA sequencing analysis, the expression level of IL-1β was validated by enzyme-linked immunosorbent assay (ELISA) and western blot. (2) The dose-response curves of IL-1β inhibitor diacerein were evaluated by cell counting kit-8 (CCK-8) assays in OVCAR3 and CAOV3 cells. CCK-8 assays were further applied to determine the viabilities of OVCAR3 and CAOV3 cells. (3) To evaluate the synergistic effects of olaparib and IL-1β inhibitor in vivo, the transplanted ovarian cancer model was constructed. BALB/c-nude mice ( n=16) were injected intraperitoneally with 1×10 7 OVACR3 cells labelled with luciferase (OVCAR3-Luc). Immunohistochemistry (IHC) assay was performed to determine nuclear antigen associated with cell proliferation (Ki-67) expression. (4) Blood routine tests, kidney and liver function tests were performed to analyze the toxic reaction of different drug treatments. The potential drug-induced injuries of vital organs including heart, liver, spleen, lungs and kidneys of nude mice were determined by hematoxylin-eosin (HE) staining. Results:(1) The RNA sequencing results showed that the mRNA level of IL-1β was the most significantly increased among the 25 differentially expressed genes in OVCAR3 cells treated with olaparib, compared to the negative control group. Olaparib treatment significantly promoted the secretion and expression of IL-1β protein in both OVACR3 and CAOV3 cells by ELISA [(36.2±3.5) and (49.5±3.5) pg/ml, respectively; all P<0.001] and western bolt (2.87±0.37 and 2.05±0.08, respectively; all P<0.01). (2) The half maximal inhibitory concentration (IC 50) value of IL-1β inhibitor was determined as follows: 75 μmol/L for OVACR3 cells and 100 μmol/L for CAOV3 cells. The treatments were divided into four groups including control group, olaparib monotherapy group, IL-1β inhibitor monotherapy group and the combination therapy group. The cell viabilities of each group in OVCAR3 and CAOV3 were determined by CCK-8 assay. The data in each group were showed as follows for OVCAR3 and CAOV3 cells: (100.0±0.4)% and (100.0±3.5)% in control group; (63.1±6.2)% and (63.3±3.8)% in olaparib monotherapy group; (61.6±4.7)% and (63.8±3.5)% in IL-1β inhibitor monotherapy group; and (32.9±5.2)% and (30.0±1.3)% in the combination therapy group. The viability assay showed that the combined strategy exhibited a significant inhibition effect on OVACR3 and CAOV3 cells, compared to the monotherapy group and the control group (all P<0.01). (3) All mice with transplanted tumors of HRD-proficient ovarian cancer cells were randomly divided into four groups, and treated with four different treatments as mentioned above, respectively. After 4 weeks (on day 29), the vivo fluorescence imaging were determined. The results showed that the amount of fluorescence of transplanted tumors was mostly decreased in the combination therapy group [(0.5±0.4)×10 10 p/s], compared to the control group [(4.2±1.0)×10 10 p/s] or the groups treated with any single drug [(3.1±0.9)×10 10, (2.2±0.9)×10 10 p/s; all P<0.05]. Mice were then sacrificed under anesthesia, and all transplanted tumors detached and weighed for further investigation. The weight of transplanted tumors was significantly decreased in the combination therapy group [(0.09±0.03) g], compared to that in control group [(0.25±0.05) g] or groups treated with any single drug [(0.17±0.03), (0.19±0.04) g; all P<0.05]. The measurement of the expression of Ki-67 showed that it was significantly decreased in the combination therapy group (0.33±0.10), compared to that in the control group (1.00±0.20) or monotherapy groups (0.76±0.07, 0.77±0.12; all P<0.05). (4) There were no significant differences of body weights, blood routine test, renal and liver function tests among mice with different treatments (all P>0.05). Moreover, no significant injuries were observed in the vital organs among the four groups. Conclusions:The combination of olaparib and IL-1β inhibitor synergistically exhibits significant cytotoxicity in HRD-proficient ovarian cancer cells. Moreover, the blood routine and blood biochemistry results confirmed the biosafety of the combination of olaparib and IL-1β inhibitor.