Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Objective: To analyze the effects of blue light on the formation of kidney stones. Methods: A total of 40 rats were randomly divided into 4 groups：A，B，C，and D，with 10 rats in each group.Rats in groups C and D were administered with a mixture of 10 g/L ethylene glycol，20 g/L ammonium chloride，and 100 g/L calcium gluconate via gavage (2 mL per mouse)，while rats in groups A and B received an equal volume of physiological saline via gavage.From the second day after gavage，rats in groups A and C were subjected to twice-daily blue light irradiation (one hour per session) as an intervention，while rats in groups B and D were subjected to fluorescent lamp irradiation using the same method.After 4 weeks of intervention，the 24-hour urine samples were collected，and the rats were then euthanized for the collection of blood and kidney tissue samples.Serum levels of antidiuretic hormone (ADH)，urinary Ca ，and urinary oxalate (Oxa) were measured.Levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in kidney tissues were detected using ELISA.Von Kossa staining was performed to observe pathological changes in kidney tissues and the presence of calcium salt crystals in the kidneys. Results: Compared with groups A and B，groups C and D showed higher accumulation of calcium salt crystals in renal tissues，as well as elevated levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues, additionally，the SOD level in renal tissues was lower (P<0.05).Compared with group D，group C exhibited higher accumulation of calcium salt crystals in renal tissues，along with increased levels of ADH，urinary Ca ，urinary Oxa，and MDA in renal tissues；conversely，the SOD level in renal tissues was lower (P<0.05). Conclusion: Blue light may increase the formation of kidney stones in rats by promoting the secretion of ADH in serum and oxidative stress in kidney tissues through the brain-kidney axis.

ObjectiveTo investigate the association between triglyceride-glucose (TyG) index and the risk of stroke in middle-aged and elderly individuals with hypertension, so as to provide more evidence for the prevention and treatment of stroke. MethodsMiddle-aged and elderly hypertensive individuals who took part in all four surveys in 2011, 2013, 2015, and 2018 were selected as the research subjects based on data from the China Health and Retirement Longitudinal Study (CHARLS). Participants were divided into four groups (≤Q1， >Q1~Q2， >Q2~Q3， and >Q3) based on TyG index quartiles, and the cumulative risk of stroke in different groups was analyzed using the Kaplan-Meier method. Different Cox proportional hazards regression models were constructed to analyze the relationship between the TyG index and stroke risk. Sensitivity analysis were performed to evaluate the robustness of the results. ResultsA total of 4 596 participants were included in the study. Among them, 338 individuals (7.35%) had a stroke during the 7-year follow-up period. The cumulative risk of stroke increased with higher TyG index levels. Results from the Cox regression models indicated that higher TyG levels were associated with an increased risk of stroke among middle-aged and elderly individuals with hypertension. Compared with the lowest TyG index quartile (≤Q1: TyG index ≤8.33) group, the highest quartile (>Q3: TyG index >9.17) group showed a 45.10% increased risk of stroke (HR=1.451, 95% CI:1.017‒2.072). ConclusionA higher TyG index is associated with an increased risk of stroke in middle-aged and elderly individuals with hypertension.

Aim To explore the relationship between multiple cardiovascular and metabolic diseases and falls in middle-aged and elderly people.Methods Using the fifth dataset of the China Health and Retirement Longitudinal Study(CHARLS),18 968 middle-aged and elderly people aged 45 years and above were enrolled as study subjects.The relationship between multiple cardiovascular and metabolic diseases and falls was analyzed by Logistic regression model.Results The incidence rates of falls,severe falls and hip fractures in the study subjects were 17.3％,6.8％and 0.9％,respectively.Cardiovascular and metabolic diseases were positively associated with the risk of falls.Compared with study subjects without cardiovascular and metabolic diseases,those with 1,2,3 and 4 cardiovascular and metabolic disea-ses had a 13％,44％,69％and91％increased risk of falls,respectively,with OR(95％CI)of 1.13(1.02～1.25),1.44(1.29～1.61),1.69(1.48～1.93)and 1.91(1.56～2.32);the risk of serious falls increased by 22％,51％,69％and 102％,respectively,with OR(95％CI)of 1.22(1.05～1.42),1.51(1.27～1.78),1.69(1.38～2.05)and 2.02(1.54～2.66).The risk of hip fractures increased by 95％,147％and 157％in study subjects with2,3 and 4 cardiovascular and metabolic diseases,respectively,with OR(95％CI)of 1.95(1.24～3.05),2.47(1.50～4.07)and 2.57(1.26～5.20).Conclusion Multiple cardiovascular and metabolic diseases significantly increased the risk of falls in middle-aged and elderly people.

This study aims to analyze the screening results and epidemiological characteristics of prostate cancer (PCa) among elderly males in the rural areas of Songjiang, Shanghai City, through the implementation of a preliminary prostate-specific antigen (PSA) screening based on a community-linkage model, and to explore an effective screening approach. A retrospective observational study design was employed to collect data from residents who underwent PSA screening at Songjiang Hospital affiliated to Shanghai Jiao Tong University School of Medicine, in collaboration with multiple community health service centers in Songjiang District, Shanghai City, between June 2022 and June 2024, through free clinics and annual health examinations. Prostate biopsy was recommended for individuals with total PSA (tPSA) levels >10 ng/ml and those with 4 ng/ml≤tPSA≤10 ng/ml and abnormal free-to-total PSA (f/tPSA) ratios. Clinical characteristics of detected PCa patients were analyzed. Follow-up was conducted through phone calls and home visits by family doctors, coupled with enhanced health education. The results indicated that a total of 17 198 residents participated in the screening, among which 2 234 (12.99%) had tPSA levels between 4 ng/ml and 10 ng/ml, and 257 (1.49%) had tPSA levels >10 ng/ml. Ultimately, 417 residents underwent prostate biopsy, with 171 being diagnosed with PCa, yielding a positive biopsy rate of 41.00% and a PCa detection rate of 0.99%. The predominant pathological subtype among PCa patients was adenocarcinoma (168 cases, 98.24%). Of the 146 PCa patients who received treatment, the majority were classified as intermediate or high-risk (124 cases, 84.93%). Furthermore, with the optimization of the screening model, there was a significant increase in the proportion of subsequent outpatient visits. In conclusion, the community-linkage-based PSA screening model demonstrated high effectiveness in screening for PCa among elderly males in the rural areas of Songjiang, Shanghai City. Epidemiological findings revealed that PCa patients in this region are primarily composed of intermediate and high-risk groups, highlighting the need for intensified early screening and health education.

Aim To explore the relationship between multiple cardiovascular and metabolic diseases and falls in middle-aged and elderly people.Methods Using the fifth dataset of the China Health and Retirement Longitudinal Study(CHARLS),18 968 middle-aged and elderly people aged 45 years and above were enrolled as study subjects.The relationship between multiple cardiovascular and metabolic diseases and falls was analyzed by Logistic regression model.Results The incidence rates of falls,severe falls and hip fractures in the study subjects were 17.3％,6.8％and 0.9％,respectively.Cardiovascular and metabolic diseases were positively associated with the risk of falls.Compared with study subjects without cardiovascular and metabolic diseases,those with 1,2,3 and 4 cardiovascular and metabolic disea-ses had a 13％,44％,69％and91％increased risk of falls,respectively,with OR(95％CI)of 1.13(1.02～1.25),1.44(1.29～1.61),1.69(1.48～1.93)and 1.91(1.56～2.32);the risk of serious falls increased by 22％,51％,69％and 102％,respectively,with OR(95％CI)of 1.22(1.05～1.42),1.51(1.27～1.78),1.69(1.38～2.05)and 2.02(1.54～2.66).The risk of hip fractures increased by 95％,147％and 157％in study subjects with2,3 and 4 cardiovascular and metabolic diseases,respectively,with OR(95％CI)of 1.95(1.24～3.05),2.47(1.50～4.07)and 2.57(1.26～5.20).Conclusion Multiple cardiovascular and metabolic diseases significantly increased the risk of falls in middle-aged and elderly people.

AIM To prepare fisetin-loaded nanostructured lipid carriers,and to evaluate their in vivo pharmacokinetics.METHODS Ethanol injection method was applied to preparing the nanostructured lipid carriers.With monostearin-phospholipid ratio,monostearin-triacetin ratio and D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)concentration as influencing factors,encapsulation efficiency as an evaluation index,the formulation was optimized by Box-Behnken response surface method.The crystal form was analyzed by X-ray powder diffraction,after which the morphology was observed by transmission electron microscopy,infrared spectroscopy analysis was performed,the drug relaese was investigated by dialysis bag method,and the stability was determined.Eighteen rats were randomly assigned into 3 groups and given intragastric administration of the 0.5％CMC-Na suspensions of fisetin and its phospholipid complex,nanostructured lipid carriers(150 mg/kg),respectively,after which blood collection was made at0.25,0.5,1,1.5,2,3,4,6,8,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of fisetin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 1.56∶1 for monostearin-phospholipid ratio,3.05∶1 for monostearin-triacetin ratio,and 0.2 mg/mL for TPGS concentration.The nearly round fisetin-loaded nanostructured lipid carriers demonstrated the average encapsulation efficiency,drug loading,particle size and Zeta potential of(86.14±1.28)％,(8.96±0.26)％,(212.35±9.04)nm and-(31.13±1.16)mV,respectively.Raw medicine existed in the nanostructured lipid carriers in an amorphous state,preparation process did not affect the hydrogen bonding between raw medicine and phospholipids.The nanostructured lipid carriers displayed the accumulative release rate of 46.12％within 3 h in simulated gastric juice,and that of about 50％within 18 h in simulated intestinal fluid,whose freeze-dried powder exhibited good stability after being placed for 6 months.Compared with raw medicine and phospholipids complex,the nanostructured lipid carriers displayed prolonged tmax,t1/2(P＜0.01)and increased Cmax,AUC0-t,AUC0-∞(P＜0.01),whose relative bioavailability was enhanced to 7.07 times.CONCLUSION Nanostructured lipid carriers can improve the oral bioavailability of fisetin.

AIM To prepare fisetin-loaded nanostructured lipid carriers,and to evaluate their in vivo pharmacokinetics.METHODS Ethanol injection method was applied to preparing the nanostructured lipid carriers.With monostearin-phospholipid ratio,monostearin-triacetin ratio and D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)concentration as influencing factors,encapsulation efficiency as an evaluation index,the formulation was optimized by Box-Behnken response surface method.The crystal form was analyzed by X-ray powder diffraction,after which the morphology was observed by transmission electron microscopy,infrared spectroscopy analysis was performed,the drug relaese was investigated by dialysis bag method,and the stability was determined.Eighteen rats were randomly assigned into 3 groups and given intragastric administration of the 0.5％CMC-Na suspensions of fisetin and its phospholipid complex,nanostructured lipid carriers(150 mg/kg),respectively,after which blood collection was made at0.25,0.5,1,1.5,2,3,4,6,8,12 h,UPLC-MS/MS was adopted in the plasma concentration determination of fisetin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 1.56∶1 for monostearin-phospholipid ratio,3.05∶1 for monostearin-triacetin ratio,and 0.2 mg/mL for TPGS concentration.The nearly round fisetin-loaded nanostructured lipid carriers demonstrated the average encapsulation efficiency,drug loading,particle size and Zeta potential of(86.14±1.28)％,(8.96±0.26)％,(212.35±9.04)nm and-(31.13±1.16)mV,respectively.Raw medicine existed in the nanostructured lipid carriers in an amorphous state,preparation process did not affect the hydrogen bonding between raw medicine and phospholipids.The nanostructured lipid carriers displayed the accumulative release rate of 46.12％within 3 h in simulated gastric juice,and that of about 50％within 18 h in simulated intestinal fluid,whose freeze-dried powder exhibited good stability after being placed for 6 months.Compared with raw medicine and phospholipids complex,the nanostructured lipid carriers displayed prolonged tmax,t1/2(P＜0.01)and increased Cmax,AUC0-t,AUC0-∞(P＜0.01),whose relative bioavailability was enhanced to 7.07 times.CONCLUSION Nanostructured lipid carriers can improve the oral bioavailability of fisetin.

Objective The high incidence, disability, and mortality rates of stroke result in a heavy economic and social burden. The aim of this study was to investigate the relationship between triglyceride-glucose (TyG) index and new-onset stroke to assist in the identification of high-risk groups for stroke and to provide ideas for effective prevention. Methods The study was based on data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018 and included 7630 eligible middle-aged and elderly participants. The association between TyG index and new-onset stroke was assessed by logistic regression modelling and restricted triple spline analysis. Results A total of 431 participants had a new stroke. The TyG index was found to be a risk factor for stroke occurrence when it was >8.523, and there was a positive linear association moderated by gender. Conclusion Elevated TyG index is a risk factor for new stroke. This study provides new ideas for the identification of high-risk groups for stroke and for intervention measures and timing.