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.

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.

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 systematically evaluate the risk prediction models for postoperative pulmonary infection in patients with esophageal cancer, providing an objective basis for clinical selection and optimization of models. Methods A systematic search was conducted in Chinese and English databases such as VIP, Wanfang, CNKI, CBM, PubMed, Cochrane Library, Embase, and Web of Science for studies related to the risk prediction models of postoperative pulmonary infection in patients with esophageal cancer from the inception to September 30, 2024. The PROBAST tool was used to assess the quality of prognostic model research, and the RevMan 5.4 software was used for meta-analysis of predictive factors. Results A total of 17 articles were included, containing 26 pulmonary infection risk prediction models. The area under the receiver operating characteristic curve (AUC) ranged from 0.627 to 0.942, among which 21 models had good predictive performance (AUC>0.7). Quality assessment through the PROBAST tool revealed that all 17 articles had a high risk of bias. Meta-analysis results showed that common predictive factors for postoperative pulmonary infection in esophageal cancer included smoking history (OR=1.97), smoking index ≥200 (cigarettes-years) (OR=4.38), smoking index ≥400 (cigarettes-years) (OR=2.00), age (OR=1.27), comorbid diabetes (OR=2.13), comorbid emphysema or chronic obstructive pulmonary disease (OR=1.55), low plasma albumin levels (OR=1.17), prognostic nutritional index (OR=4.45), history of related lung diseases (OR=2.10), tumor location (OR=2.32), surgical approach (OR=2.21), operation time (OR=1.73), preoperative serum procalcitonin levels (OR=3.06), anastomotic leakage (OR=3.39), reduced forced expiratory volume in the first second/forced vital capacity ratio (OR=0.86), and hoarseness (OR=2.23). Conclusion At present, the risk prediction models for postoperative pulmonary infection in esophageal cancer are still in the stage of continuous development and optimization, and their research quality needs to be further improved. Future research can refer to the predictive factors summarized in this study based on meta-analysis, combined with clinical practice, to select appropriate methods to construct and validate the risk prediction models for postoperative pulmonary infection in esophageal cancer, thus providing early targeted preventive strategies for high-risk patients.

Abstract The cooccurrence of multi disease among children and adolescents has become increasingly prominent, necessitating a shift from "single disease separate treatment" to "multi disease co prevention". Focusing on four common health problems in children and adolescents, namely, myopia, depression, overweight/obesity, and spinal abnormalities, the paper systematically reviews the association between four categories of factors, society, environment, family, and individual behavior, and the co occurrence of the aforementioned health problems. The findings indicate that particulate matter 2.5 exposure, light at night, physical inactivity, excessive screen time, and unhealthy diet constitute the primary cross dimensional risk network. Based on these findings, the paper proposes a collaborative action framework involving family, school, and society, emphasizing systematic strategies ranging from upstream environmental governance to downstream behavioral intervention, so as to provide evidence for the practice and policy making of multi disease co-prevention in children and adolescents.

Objective: To investigate the stability of plasma from blood donors cryopreserved at-80℃for two months in ELISA and NAT detection (HBV, HCV, and HIV), and to provide a reference for the preservation, transportation, and retrospective testing of samples collected in remote areas or during emergency blood collection. Methods: Three sets of experimental designs were adopted, each including ELISA (HBsAg, anti-HCV, HIV Ag-Ab) and NAT (HBV DNA, HCV RNA, HIV-1 RNA) testing. Stability validation test: 136 positive and 150 negative donor samples were selected, retested with the original reagents after cryopreservation at-80℃for two months, and the ELISA S/CO values, NAT Ct values, and result concordance rates before and after freezing were compared. Limit of detection validation test: Standard substances with known concentrations were diluted into three gradients of weakly reactive samples (ELISA S/CO values of 0.8-5, NAT Ct values of 35-42). Each was tested six times before and after freezing, the mean values were calculated, and the ELISA S/CO values and NAT Ct values were compared. Real-world validation test: 300 randomly selected donor samples were subjected to plasma separation after initial testing and cryopreserved for two months. The reactive detection rates of ELISA and NAT before and after freezing were compared. Results: Stability validation test: In ELISA testing, 3 samples converted from weak-positive to negative, and 3 samples converted from weak-positive to gray zone, yielding a concordance rate of 97.9%. In NAT testing, 2 samples converted from weak-positive to gray zone, yielding a concordance rate of 99.30%. Significant differences were observed in both ELISA S/CO values and NAT Ct values after freezing (P<0.05). Limit of detection validation test: No significant differences were found in ELISA S/CO values or NAT Ct values for the three concentrations of weakly reactive samples before and after freezing (P>0.05); only the anti-HCV ELISA result for the 0.5 NCU/mL sample converted from positive to the gray zone. Real-world validation test: The ELISA reactive detection rates before and after freezing were 1.67% vs 1.00%, and the NAT reactive detection rates were 0.33% vs 0.33%, with no significant differences (P≥0.05). Conclusion: After cryopreservation of donor plasma at-80℃for two months, the overall concordance rates for ELISA and NAT testing are extremely high. Although weak-positive samples are susceptible to freezing effects, the overall qualitative results remain stable, demonstrating that deep-low temperature cryopreservation can effectively maintain the stability of viral marker detection.

Objective:To evaluate the changes in left ventricular structure and function in pregnant women with different severities of hypertensive disorders of pregnancy（HDP）using conventional echocardiographic parameters，strain，and tissue-tracking mitral annulus displacement（TMAD）parameters，and to validate and compare the application value of strain and TMAD parameters.Methods:A total of 148 singleton pregnant women with HDP and 100 healthy pregnant women（HP group）who attended the Third Affiliated Hospital of Zhengzhou University from October 2023 to July 2024 were selected. Conventional echocardiographic parameters，strain，and TMAD parameters were collected. Based on the severity of the disease，HDP patients were divided into the gestational hypertension group（GH group， n=49），non-severe preeclampsia group（NSPE group， n=35），and severe preeclampsia group（SPE group， n=64）. The differences in various parameters between the HP，GH，NSPE，and SPE groups were compared. The correlation between the displacement ratio of the midpoint of the mitral valve annulus in the apical 4-chamber（AP4 Midpt%），the displacement ratio of the midpoint of the mitral valve annulus in the apical 2-chamber（AP2 Midpt%）and left ventricular global longitudinal strain（LVGLS）were analyzed，and ROC curves were plotted to analyze and compare the diagnostic efficacies of LVGLS，AP4 Midpt% and AP2 Midpt% for left ventricular function changes in HDP pregnant women. Results:① The analysis revealed no statistically significant differences in maternal age and height between the HP group and the HDP subgroups（all P>0.05）. In contrast，statistically significant differences were observed in gestational age，systolic blood pressure，diastolic blood pressure，body mass index，and body surface area（all P<0.05）. Additionally，significant differences were noted in left ventricular mass，left ventricular interventricular septum thickness at end-diastole，left ventricular posterior wall thickness at end-diastole，left ventricular end-diastolic dimension，left ventricular end-systolic dimension，left ventricular end-diastolic volume，left ventricular end-systolic volume，and stroke volume between the HP group and the HDP subgroups（all P<0.05），while the difference in left ventricular ejection fraction was not statistically significant（ P>0.05）. ② Significant differences were identified in strain and TMAD parameters between the HP group and the HDP subgroups（all P<0.05），with LVGLS，AP4 Midpt% and AP2 Midpt% exhibited the largest effect sizes（ η p2=0.457，0.453，0.351）. A progressive decline in strain and TMAD parameters was observed as the severity of HDP increased. ③ There were strong positive correlations between AP4 Midpt%，AP2 Midpt% and LVGLS（ r=0.752，0.747；all P<0.001）. ④ LVGLS，AP4 Midpt% and AP2 Midpt% all demonstrated significant diagnostic efficacies for changes in left ventricular function in HDP（AUC=0.840，0.847，0.791），and the differences in AUC among the 3 curves were not statistically significant（all P>0.05）.⑤ The success rate of collecting TMAD parameters was significantly higher than that of strain parameters（99.24% vs. 93.58%， P<0.001）. Conclusions:As the severity of the disease worsens，the changes of left ventricular structure and function in pregnant women with HDP become more and more significant. Both strain and TMAD parameters can early and sensitively identify the subclinical damage of left ventricular systolic function in HDP pregnant women，and both of them have the same diagnostic value. TMAD parameters can be used as a reliable substitute parameter of LVGLS in HDP pregnant women.

Objective·To investigate the changes in transcriptome and chromatin accessibility during the differentiation of human embryonic stem cells(hESCs)into neural progenitor cells(NPCs)using in vitro differentiation models and high-throughput multi-omics sequencing technologies.Methods·hESCs were first induced to differentiate into NPCs in vitro using the embryoid body formation method,and cells at both stages were collected.The cell phenotypes were identified by reverse transcription-quantitative real-time PCR(RT-qPCR)and immunofluorescence(IF)staining.Transcriptome sequencing(RNA-seq)was conducted to detect and analyze the differentially expressed genes(DEGs)between hESCs and NPCs.The assay for transposase-accessible chromatin with high-throughput sequencing(ATAC-seq)was employed to assess chromatin accessibility changes between hESCs and NPCs.Motif enrichment analysis was performed on differentially accessible chromatin regions to discover potential regulatory transcription factors.Finally,an integrated analysis of RNA-seq and ATAC-seq data and the protein-protein interaction(PPI)network were performed to identify key genes and regulatory pathways involved in the early stages of neural differentiation in vitro.Results·Both RT-qPCR and IF results indicated that the expression levels of pluripotency markers(NANOG and POU5F1)were high at the hESC stage but significantly decreased at the NPC stage,while early neural differentiation markers(PAX6,SOX1,and NES)were minimally expressed at the hESC stage but markedly upregulated at the NPC stage.RNA-seq analysis revealed that compared to the hESC stage,there were 5 597 genes upregulated and 3 654 genes downregulated at the NPC stage.Gene function enrichment analysis showed that the upregulated genes at the NPC stage were enriched in the functions related to neural development.ATAC-seq analysis demonstrated a total of 27 491 genomic regions had significant changes in chromatin accessibility during the differentiation from hESC to NPC,with 12 381 regions showing increased accessibility and 15 110 regions showing decreased accessibility.Motif enrichment analysis revealed that transcription factor genes such as DLX1 and LHX2 might play an important role in the differentiation process from hESCs into NPCs.Integrated analysis of RNA-seq and ATAC-seq data revealed that overlapping genes with high expression at the NPC stage were mainly enriched in axon guidance,forebrain development,and neuron migration.After neural differentiation,the expression levels of CTNND2 and LHX2 genes increased,and the chromatin accessibility of related genomic regions also increased.PPI network analysis indentified candidate downstream genes including PRKACA,CDH2,and ERBB4.Conclusion·The in vitro differentiation model of hESCs combined with high-throughput multi-omics sequencing technologies can be used to depict the changes in transcriptome and chromatin accessibility during the differentiation of hESCs into NPCs.In this process,the expression levels of genes related to axon guidance,forebrain development,and neuronal migration pathways increase and related chromatin accessibility is enhanced.

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.