ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

This study aimed to investigate the effects of zidovudine (AZT) on high-fat diet (HFD)-induced metabolic disturbances in rats and its underlying mechanisms. The HFD rat model was established, and the animals were divided into the control group, the model group, and the AZT-treated group at low (25 mg/kg) and high (50 mg/kg) doses. Metabolic phenotype, hepatic lipid deposition, oxidative stress, mitochondrial function, and peroxisome proliferator-activated receptor (PPAR) signaling were evaluated. AZT treatment significantly mitigated HFD-induced body weight gain and reduced both the mass and adipocyte size of inguinal and epididymal white adipose tissues; it also enhanced metabolic flexibility and improved glucose tolerance without elevating blood lactate levels. High-dose AZT further lowered hepatic triglyceride accumulation, ameliorated steatosis, and additionally, attenuated hepatic oxidative stress by increasing superoxide dismutase (SOD) activity and decreasing malondialdehyde (MDA) levels. Western blot analysis revealed that AZT upregulated hepatic PPARα and carnitine palmitoyltransferase 1α (CPT1α), while downregulating PPARγ expression. In conclusion, AZT effectively ameliorates HFD-induced metabolic disorders without inducing mitochondrial toxicity, which may be related to the promotion of fatty acid oxidation, the reduction of oxidative stress, and the modulation of both the PPAR signaling pathway and pyrimidine metabolism.

With the aging population and the widespread implementation of lung cancer screening programs, an increasing number of elderly patients are undergoing curative lung resection. Due to diminished physiological reserve and complex comorbidities, this demographic exhibits a significantly higher incidence of severe perioperative complications (defined as Clavien-Dindo grade≥Ⅲ), which adversely affects both perioperative safety and long-term prognosis. In recent years, the research paradigm has shifted from univariate analysis toward multidimensional risk integration and the development of predictive models. This article systematically reviews the key risk factors for severe perioperative complications in elderly lung cancer patients, encompassing biological aging processes, frailty and sarcopenia, cardiopulmonary and renal functional reserves, inflammatory-immune and coagulation status, and perioperative interventions. Furthermore, it traces the evolution of risk assessment tools from traditional regression models to machine learning models that integrate multimodal data. The review also discusses common challenges in this field, including the standardization of outcome definitions, external validation, calibration assessment, and clinical translation. Future efforts should prioritize the deep integration of predictive tools with clinical decision support systems to establish a closed-loop care pathway from risk identification to stratified intervention, thereby effectively reducing complication rates and enhancing surgical outcomes for elderly lung cancer patients.

Objective To compare the efficacy and safety of the transperineal four-hole prostate puncture with conventional transperineal prostate puncture. Methods A total of 91 patients undergoing transperineal prostate puncture at the Second Hospital of Hebei Medical University during Jan. 2024 and Jan. 2025 were enrolled. Based on the puncture methods, the patients were divided into the four-hole group(n=46)and conventional group(n=45). The four-hole group underwent four-hole puncture, while the conventional group received standardized parallel needle insertion. The operation time, intraoperative blood loss, pain score, positive biopsy rate, and complications were compared between the two groups. Results The intraoperative blood loss [(7.05±2.48)mL vs.(9.15±3.49)mL] and pain score [(2.33±1.55)vs.(3.02± 1.54)] of the four-hole group were significantly lower than those of the conventional group(P＜0.05). No significant differences were observed in the positive biopsy rate [47.8%(22/46)vs. 46.7%(21/45)] or operation time [(18.83±2.49)min vs.(18.07±1.66)min](P＞0.05). The total complication rate in the four-hole group was significantly lower than that in the conventional group [21.7%(10/46)vs. 42.2%(19/45), P＜0.05]. Conclusion Compared with the conventional parallel needle insertion method, the four-hole puncture technique reduces the intraoperative blood loss, alleviates trauma severity and pain response, and reduces the complication rate.

Objective: To explore the brain-predicted age difference (Brain-PAD) in patients with type 2 diabetes mellitus (T2DM) by a machine learning prediction model based on structural magnetic resonance ( sMRI) in the Southwest University Adult Lifespan Dataset (SALD) , and to reveal the relationship between Brain-PAD and dura- tion of T2DM and cognition . Methods: Group comparisons about demographic variables and cognitive function were conducted respectively in local database of 104 T2DM patients and 83 healthy controls (HC) . The prediction model via Gaussian process regression (GPR) was constructed by training sMRI data of 329 healthy volunteers in SALD , then its performance was validated and evaluated . Furthermore , Brain-PAD ( predicted age-chronological age) in the local database was calculated . Group comparisons of Brain-PAD between T2DM patients and HCs were conducted by Mann-Whitney U test. Finally , Pearson correlation coefficient (r) was calculated between Brain-PAD and duration of disease and cognition . Results: Poor performance in auditory verbal learning test (AVLT)-delayed recall , AVLT-recognition , symbol digital modalities test (SDMT) (P < 0. 05) , and increased Brain-PAD were ob- served in T2DM patients , compared with HCs [1 . 619 ( - 4. 001 , 8. 272) years vs - 1 . 289 ( - 4. 128 , 4. 134) years , Z = 2. 056 , P = 0. 034] . Notably , the median of Brain-PAD in T2DM group was positive , indicating that the brain of T2DM patient maybe relatively “older”than his chronological age . Brain-PAD in T2DM group was as- sociated with performance in AVLT-immediate recall ( r = 0. 291 , P = 0. 003) , AVLT-delayed recall ( r = 0. 248 , P = 0. 011) , SDMT( r = 0. 376 , P = 0. 001) and trail making test (TMT)-A ( r = - 0. 206 , P = 0. 036) . However , the relationships between Brain-PAD and duration of T2DM were not explored . Conclusion Decreased cognitive function in patients with T2DM is demonstrated in this study . The machine learning prediction model based on sMRI supports the identification of brain aging objectively in patients with T2DM .

Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To construct analytical dimensions for policy texts related to the pilot work of Health Impact Assessment (HIA) system in Zhejiang Province and conduct quantitative analysis, thereby providing references for improving the pilot work.Methods:Policy texts issued by Zhejiang Province between February 11, 2018, and February 29, 2024, which involved HIA content, were selected. The policy instruments theory was employed to construct an analytical framework around the dimensions of policy instruments, policy objectives, policy actors, and the interactions between policy instruments and policy objectives, and between policy instruments and policy actors. Based on this framework, a combination of literature analysis and content analysis was used to conduct a multi-dimensional quantitative analysis of the policy texts related to the pilot work of HIA system in Zhejiang Province.Results:Fifty core policy texts were included and 1 588 codes were obtained. In terms of policy instruments, environmental-type instruments were the most widely used (852 items), with internal responsibilities and methodological measures being the most frequently used; supply-type instruments were the second most used (459 items), with mechanism improvement being the most frequently used; demand-type instruments were the least used (277 items), with multi-stakeholder participation being the most frequently used. In terms of policy objectives, the objective of system construction dominated (701 articles, accounting for 56.45%), while the proportion of policy coverage, evaluation technology, and effectiveness evaluation was relatively low. In terms of policy subjects, the Party committee and government were the main policy subjects (434 articles, accounting for 39.20%), followed by health departments and public policy-making departments, while the proportion of public health institutions and social forces was extremely low. In the interaction between policy instruments and policy objectives, policy coverage, system construction, and effectiveness evaluation objectives all responded most frequently to environmental-type instruments, while the evaluation technology objectives responded more frequently to supply-type instruments. In the interaction between policy instruments and policy subjects, the Party committee and government played a dominant role in the use of policy instruments, with the health department and public policy-making department in the middle.Conclusions:The pilot work of the HIA system in Zhejiang Province presented a " environment-driven, system-construction-priority, Party-committee-and-government-led" policy characteristic. The main challenges were the imbalanced structure of policy instruments, insufficient synergy among policy objectives, and the need for greater participation of multiple stakeholders.

Objective:To understand the changes in the prevelance smoking in people aged ≥15 years in Baoji, and provide evidence for the improvement of tobacco control strategies.Methods:Data were from the sampling survey of chronic diseases and their risk factors conducted in Baoji at an interval of five years from 2013 to 2023. The survey used multi-stage cluster random sampling method to select local people aged ≥15 years, and the information about their tobacco use were collected by face-to-face interview. Descriptive epidemiological methods were used to analyze the prevalence of smoking, and χ2 test was used to analyze the change trend. Results:The smoking rate in people aged ≥15 years in Baoji decreased from 2013 to 2023, and the standardized smoking rate decreased by 13.6% in 2023 compared with 2013. The standardized smoking cessation rate increased by 13.4% in 2018 compared with 2013, and the standardized smoking cessation rate decreased by 7.3% in 2023 compared with 2018. The standardized passive smoking rate decreased by 15.1% in 2018 compared with 2013, and the standardized passive smoking rate increased by 8.8% in 2023 compared with 2018. The average daily smoking amount increased by 3.7 cigarettes in 2018 compared with 2013, and the average daily smoking amount decreased by 3.9 cigarettes in 2023 compared with 2018.Conclusion:Progress has been made in tobacco control in Baoji, but problems still exist in tobacco control, to which close attention needs to be paid.

Objective:To explore the moderating and mediating roles of psychological resilience in the relationship between job satisfaction and depressive symptoms among petrochemical workers.Methods:In April 2022, a cluster sampling method was used to conduct a questionnaire survey among 1087 in-service employees of a petrochemical enterprise in Henan Province. A total of 861 questionnaires were recovered, including 857 valid ones, with an effective rate of 99.54%. Data on job satisfaction, psychological resilience, and depressive symptoms were collected using the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), Job Satisfaction Questionnaire, and Patient Health Questionnaire-9 (PHQ-9). Spearman rank correlation analysis was applied to analyze the relationships among the scores of job satisfaction, psychological resilience, and depressive symptoms. Hierarchical linear regression analysis was used to test the moderating effect of psychological resilience, and the Bootstrap method was employed to verify the mediating effect of psychological resilience.Results:The scores of job satisfaction, psychological resilience, and depressive symptoms among petrochemical workers were 36.00 (31.00, 36.00) points, 36.00 (30.00, 41.00) points, and 7.00 (3.00, 9.00) points. The detection rate of depressive symptoms was 65.7% (563/857). Results of Spearman rank correlation analysis showed that job satisfaction of petrochemical workers was positively correlated with psychological resilience ( rs=0.270, P<0.01) and negatively correlated with depressive symptoms ( rs=-0.386, P<0.01), psychological resilience was negatively correlated with depressive symptoms ( rs=-0.515, P<0.01). Results of hierarchical linear regression analysis indicated that psychological resilience had no moderating effect on the relationship between job satisfaction and depressive symptoms of petrochemical workers ( b=0.001, P>0.05). Results of the mediating effect test showed that psychological resilience played a partial mediating effect in the relationship between job satisfaction and depressive symptoms ( P<0.01), with a mediating effect value of -0.071 (95% CI: -0.125, -0.045), accounting for 20.16% of the total effect. Conclusion:Psychological resilience exerts a partial mediating effect rather than a moderating effect in the relationship between job satisfaction and depressive symptoms among petrochemical workers.