OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

ObjectiveTo develop a novel clinical predictive model for metabolic dysfunction-associated fatty liver disease （MAFLD） based on metabolic markers and anthropometric indicators， and to provide a more effective tool for the early screening and intervention of MAFLD. MethodsA retrospective analysis was performed for 2 824 individuals who underwent abdominal color Doppler ultrasound at Health Examination Center of The First Hospital of Lanzhou University from January 1， 2024 to January 1， 2025， and at a ratio of 7∶3， they were randomly divided into training set with 1 976 patients and validation set with 848 patients. Clinical data， serological markers， and abdominal ultrasound results were collected from all patients， and triglyceride-glucose （TyG） index， triglyceride-to-high-density lipoprotein cholesterol （TG/HDL-C） ratio， and anthropometric indicators were calculated. The independent samples t-test was used for comparison of normally distributed or approximately normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate logistic regression analysis was used to identify independent predictive factors for MAFLD and intermediate- to high-risk MAFLD. Five risk prediction models were established for MAFLD based on the independent influencing factors， and a nomogram was plotted. The receiver operating characteristic （ROC） curve was plotted to assess model performance， and the area under the ROC curve （AUC） was calculated. The calibration curve was used to evaluate the predictive accuracy of the models， and decision curve analysis was used to assess the clinical practicability of the models. These models were then compared with traditional models. ResultsAmong the 1 976 individuals in the training set， 937 （47.42%） were diagnosed with MAFLD， and 423 （21.41%） were diagnosed with intermediate- to high-risk MAFLD； among the 848 individuals in the validation set， 406 （47.88%） were diagnosed with MAFLD. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=0.23， 95% confidence interval ［CI］： 0.13 — 0.39， P<0.05）， waist circumference （OR=1.11， 95%CI： 1.06 — 1.17， P<0.05）， alanine aminotransferase （ALT） >40 U/L （OR=2.24， 95%CI： 1.44 — 3.51， P<0.05）， high-density lipoprotein cholesterol （HDL-C） （OR=0.07， 95%CI： 0.04 — 0.15， P<0.05）， TyG index （OR=8.27， 95%CI： 5.09 — 13.44， P<0.05）， TG/HDL-C ratio （OR=0.84， 95%CI： 0.71 — 0.99， P<0.05）， A Body Shape Index （ABSI） （OR=0.45， 95%CI： 0.39 — 0.52， P<0.05）， and body roundness index （BRI） （OR=2.31， 95%CI： 1.50 — 3.55， P<0.05） were independent influencing factors for MAFLD， and male sex （OR=0.17， 95%CI： 0.10 — 0.31， P<0.05）， age （OR=1.09， 95%CI： 1.07 — 1.11， P<0.05）， hemoglobin （OR=0.98， 95%CI： 0.97 — 0.98， P<0.05）， platelet count （OR=0.81， 95%CI： 0.70 — 0.93， P<0.05）， fasting blood glucose （OR=0.80， 95%CI： 0.71 — 0.89， P<0.05）， triglycerides （OR=0.14， 95%CI： 0.07 — 0.29， P<0.05）， TG/HDL-C ratio （OR=0.78， 95%CI： 0.67 — 0.91， P<0.05）， TyG index （OR=5.26， 95%CI： 3.32 — 8.33）， waist circumference （OR=2.50， 95%CI： 1.72 — 3.61， P<0.05）， ABSI （OR=0.58， 95%CI： 0.51 — 0.66， P<0.05）， and BRI （OR=0.01， 95%CI： 0.00 — 0.21， P<0.05） were independent influencing factors for intermediate- to high-risk MAFLD. Among the five models established， model 5 （incorporating sex， ALT elevation， HDL-C， TyG index， TG/HDL-C ratio， waist circumference， and ABSI） had the best performance， with an AUC of 0.917 （95%CI： 0.905 — 0.929） in the training set and 0.911 （95%CI： 0.892 — 0.930） in the validation set. The calibration curve showed that model 5 had good predictive accuracy， and the decision curve analysis confirmed its clinical practicability. ConclusionThe predictive model for MAFLD constructed based on metabolic markers and anthropometric indicators has good discriminatory ability and can be used to assess the risk of MAFLD. In addition， this study shows that waist circumference， TyG index， TG/HDL-C ratio， ABSI， and BRI are independently associated with intermediate- to high-risk MAFLD， but further studies are needed to confirm their value in predicting liver fibrosis progression.

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

Objective To understand the level of occupational health literacy (OHL) and its influencing factors among occupational population in five key industries of tertiary industry in Putuo District of Shanghai City. Methods A total of 1 159 front-line workers, from five key industries of tertiary industry in Putuo District of Shanghai City in 2023, were selected as the research subjects using the stratified cluster random sampling method. Their OHL levels were surveyed using the Occupational Health Literacy Questionnaire of National Key Populations. Results A total of 1 159 front-line workers in key industries were surveyed, and 476 had OHL, with an overall OHL level of 41.1%. The OHL levels across four dimensions including basic knowledge of occupational health protection, healthy lifestyle and behavior, legal knowledge of occupational health, and basic skills of occupational health protection from high to low were 72.9%,44.5%,42.2%, and 31.3%, respectively. The results of multivariable logistic regression analysis showed that gender, educational level, and industry category were independent influencing factors for OHL level of the research subjects (all P<0.05). Female workers had higher OHL levels than males (P<0.05). Higher education level was associated with higher OHL level in workers (all P<0.05). Workers in industries of medical health had higher OHL level than those in couriers/delivery transportation, education and environmental health(all P<0.01). Conclusion The OHL level of occupational population in the five key industries of tertiary industry in Putuo District of Shanghai City needs to be further improved. Efforts should focus on enhancing health education on legal knowledge and basic skills of occupational health protection, with special attention to workers OHL in the transportation and courier/delivery industries and those with lower education levels.

Objective:To explore the impact of air pollution on hospital visits for mental and behavioral disorders among residents in an industrial area in Henan Province from 2016 to 2021.Methods:Daily outpatient visits data for mental and behavioral disorders were collected from Angang General Hospital in Angang Industrial Area at Anyang City between January 2016 and December 2021. And air pollutants and meteorological data during the same period were also collected. A generalized additive model was used for time-series analysis to examine the relationship between daily average concentrations of nitrogen dioxide (NO 2), sulfur dioxide (SO 2), fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), carbon monoxide (CO), and ozone (O 3) with a lag of 0 to 7 days on the number of visits for mental and behavioral disorders among residents. The single-day lag effect (lag0-lag7 d) and cumulative lag effect (lag01-lag07 d) were analyzed. The smooth cubic spline function was used to fit the exposure-response relationship, and subgroup analysis was performed according to different genders, seasons and ages. Results:A total of 26 268 hospital visits for mental and behavioral disorders were collected from the industrial area between 2016 and 2021. The daily average concentrations of SO 2, NO 2, PM 2.5, PM 10, and CO were (27.50±27.33), (43.11±18.33), (73.87±60.30), (134.01±83.81) μg/m 3, and (1.72±1.03) mg/m 3, respectively. The daily maximum 8-hour average concentration of O 3 was (82.18±53.70) μg/m 3. After controlling for long-term trends, temperature, relative humidity, day of the week effects, and holiday effects, the generalized additive model analysis showed that NO 2 had a statistically significant impact on the hospital visits for mental and behavioral disorders at lag0 d, lag2 d and lag01-lag05 d and CO had a statistically significant impact at lag0-lag3 d and lag01-lag06 d (all P<0.05). NO 2 at lag02-lag04 d and CO at lag0-lag2 d and lag01-lag04 d had statistically significant effects on the visits for neurasthenia (both P<0.05). The impacts of NO 2 at lag03-lag04 d, PM 2.5 at lag3 d and lag03-lag04 d, PM 10 at lag3 d and lag03 d, and CO at lag3 d and lag01-lag05 d on visits for generalized anxiety disorder were also statistically significant (all P<0.05). After false discovery rate (FDR) correction, it was shown that for every 10 μg/m 3 increase in NO 2 and every 0.1 mg/m 3 increase in CO, the percentage increase in visits for mental and behavioral disorders and its 95% confidence interval (95% CI) were 3.38% (0.95%-5.87%) and 0.78% (0.38%-1.17%), respectively. For every 0.1 mg/m 3 increase in CO, the visits for neurasthenia increased by 0.78% (0.27%-1.29%). For every 10 μg/m 3 increase in PM 2.5 and every 0.1 mg/m 3 increase in CO, the visits for generalized anxiety disorder increased by 1.07% (0.46%-1.68%) and 1.17% (0.37%-1.97%), respectively (adjusted P<0.05). There was a linear exposure-response relationship between NO 2 and CO and the hospital visits for mental and behavioral disorders, CO and the hospital visits for neurasthenia, and CO and PM 2.5 and the hospital visits for generalized anxiety disorder ( P<0.05 for the overall association test and P>0.05 for the non-linearity test). Stratified analysis showed that air pollutants had an impact on male patients with neurasthenia, female patients with generalized anxiety disorder, individuals aged <45 years with mental and behavioral disorders, and individuals aged ≥65 years with generalized anxiety disorder. The impact of air pollutants was greater during the cold season or winter. Conclusion:Exposure to air pollution can increase hospital visits for mental and behavioral disorders among residents in industrial areas, with a higher risk among those aged<45 years old and during the cold season.

Objective:To explore the association between serum selenium levels and total cancer risk in humans.Methods:A systematic search was conducted for Chinese and English literature on the association between selenium and cancer risk published up to December 2023 in the Chinese National Knowledge Infrastructure (CNKI), Wanfang, PubMed, EMbase, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases by using “neoplasms” “selenium” “prospective-studies” (both in English and Chinese) as keywords. The meta-analysis was performed using a random-effect model. The linear dose-response relationship was analyzed using a generalized least squares regression model, and the non-linear dose-response relationship was analyzed using a restricted cubic spline regression model. Publication bias was assessed by funnel plots and Egger′s regression asymmetry test.Results:A total of 12 prospective studies were included from 16 408 articles retrieved, including seven studies from Europe, four from America, and one from Asia, with a total of 4 586 cancer cases reported. Meta-analysis revealed an inverse association between baseline serum selenium levels and total cancer risk ( RR=0.68, 95% CI: 0.57-0.82, P=0.000). Furthermore, serum selenium was found to have a protective effect on both the incidence ( RR=0.66, 95% CI: 0.53-0.84, P=0.001) and mortality ( RR=0.70, 95% CI: 0.50-0.98, P=0.035) of total cancer. The inverse association between serum selenium and the incidence of total cancer was more pronounced in populations with low baseline serum selenium levels ( RR=0.65, 95% CI: 0.48-0.89, P=0.007). Additionally, dose-response meta-analysis showed that for every 10 μg/L increase in baseline serum selenium concentration, there was a 26% reduction in incidence of total cancer ( RR=0.74, 95% CI: 0.46-0.83, P=0.229) and a 6% reduction in mortality of total cancer ( RR=0.94, 95% CI: 0.86-0.96, P=0.229). Conclusion:Serum selenium is negatively associated with the incidence and mortality of total cancer.

Objective:To investigate the role of reactive astrocytes expressing aromatase(ARO)in the penumbra during ischemic stroke.Methods:A mouse model of middle cerebral artery occlusion(MCAO/R)was prepared using the suture method.Western blot and immunofluorescence staining were used to observe the expression of ARO in the penumbra after ischemia reperfusion.We generated a glial fibrillary acidic protein promoter-driven aromatase knock-out(GFAP-ARO-KO)mouse model in vivo.Neurologic impairment scores,rotarod test,grip strength test and adhesive removal test on the plantar surface of the paw were performed after MCAO/R modeling.Results:In wild type mice,the expression of ARO was significantly increased in astrocytes in the penumbra after MCAO/R(P<0.01).Compared to the control group,the expression of ARO in the GFAP-ARO-KO group was significantly reduced in astrocytes in the penumbra after MCAO/R.And loss of ARO increased cerebral infarction volume and aggravated sensorimotor impair-ment.Conclusion:After ischemic stroke,reactive astrocytes in the penumbra highly express ARO and play a protective role in post-ischemia reperfusion injury.

Objective:To investigate the predictive value of different obesity indicators for colorectal cancer (CRC) risk in different gender populations.Methods:This observational study was conducted within the Kailuan Study (Registration Number: ChiCTR-TNC-11001489). From July 2006 to October 2007, a total of 101,510 employed and retired individuals underwent health examinations, including gastrointestinal disease screening, hematological tests, and questionnaires, at Kailuan General Hospital and its 10 affiliated hospitals. After excluding those with incomplete data, 93,606 participants were included in this study and divided into male (74 852) and female (18 754) groups. CRC incidence was collected through physical examinations and questionnaires every two years. Each participant's follow-up period began at the time of the questionnaire and ended upon CRC diagnosis, death, or December 31, 2021. Body Mass Index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were quartiled (Q1, Q2, Q3, Q4), with Q1 serving as the control group. After adjusting for traditional risk factors such as age, total cholesterol, triglycerides, diabetes, hypertension, smoking status, alcohol consumption, and physical exercise, Cox regression models were used to calculate the correlations between BMI, waist circumference, WHR, WHtR, and CRC incidence in both male and female populations.Results:The age of all patients was (51±12) years, BMI was (25.06±3.49) kg/m 2, waist circumference was (86.94±9.97) cm, hip circumference was (97.30±8.81) cm, WHR was 0.89±0.07, and WHtR was 0.52±0.06.Female participants had significantly lower BMI, waist circumference, WHR, and WHtR compared to males, with statistically significant differences (all P<0.05). The mean follow-up duration for all participants was 15.01 (14.10±2.66) years, during which 718 CRC cases were identified, including 626 males (0.83%) and 92 females (0.49%). Cox proportional hazards models for males showed that CRC risk increased with waist circumference from Q3 (HR=1.43, 95%CI: 1.13-1.79, P=0.003) to Q4 (HR=1.45,95%CI: 1.14-1.82, P=0.002). Similarly, CRC risk increased with WHR from Q3 (HR=1.22, 95%CI: 1.01-1.53, P=0.007) to Q4 (HR=1.43, 95%CI: 1.14-1.79, P=0.002) and with WHtR from Q3 (HR=1.37, 95%CI: 1.08-1.74, P=0.009) to Q4 (HR=1.68, 95%CI: 1.33-2.12, P<0.001). For females, CRC risk increased with waist circumference from Q2 (HR=2.37, 95%CI: 1.20-4.67, P=0.012) to Q3 (HR=2.42, 95%CI: 1.21-4.84, P=0.013) but decreased in Q4 ( HR=2.08, 95%CI: 1.02-4.25, P=0.043). CRC risk increased significantly with WHR from Q2 (HR=2.20, 95%CI: 1.11-4.39, P=0.024) to Q3 (HR=2.89, 95%CI: 1.48-5.67, P=0.002) in females but was not statistically significant in Q4 ( P=0.074). Among females, CRC risk also increased significantly with WHtR in Q2 (HR=2.30, 95% CI: 1.16-4.56, P=0.017) and Q4 (HR=2.64, 95%CI: 1.32-5.29, P=0.006). There were no statistically significant differences in CRC risk associated with BMI in either male or female populations (both P>0.05). Conclusion:Waist circumference, WHR, and WHtR were better predictors of CRC risk than BMI in both male and female populations.

Objective:To investigate the association between single nucleotide polymorphism (SNP) of the protein phosphatase 1 regulatory subunit 1B( PPP1R1B) gene and schizophrenia in the Han population of northern Henan province. Methods:Utilizing Psychiatric Genomics Consortium 3 (PGC3) data, the SNPs of PPP1R1B gene which were significantly associated with schizophrenia were screened.Subsequently, totally 1 721 schizophrenia patients and 6 726 healthy controls from the Han population in northern Henan province were recruited for further analysis. The SNP rs907094, located within the PPP1R1B gene was validated, and the clinical symptoms of 386 schizophrenia patients were evaluated using the positive and negative syndrome scale (PANSS). Additionally, expression quantitative trait loci (eQTL) association analysis was conducted to explore the relationship between the rs907094 polymorphism and PPP1R1B gene expression.The PLINK v1.9, Genetic Power Calculater, SPSS 20.0 softwares were used for data analysis. Results:Significant differences in genotype AA, AG, GG(schizophrenia group: AA, 489(28.4%); AG, 848(49.3%); GG, 384(22.3%); control group: AA, 1 450(21.6%); AG, 3 386(50.3%); GG, 1 890(28.1%), χ2=45.418, P<0.05) and allele frequency(schizophrenia group: A, 1 826(53.1%); G, 1 616(46.9%); control group: A, 6 286(46.7%); G, 7 166(53.3%), χ2=43.877, P<0.05) were observed for SNP rs907094 between the schizophrenia group and control group. Individuals carrying allele A were identified to have a higher risk of developing schizophrenia compared to those carrying allele G ( OR=1.288, 95% CI=1.195-1.388). Furthermore, the genotype PPP1R1B gene was found to be associated with the clinical features of schizophrenia. A statistically significant difference was observed in the excitement/hostility factor between AA and GG patients with rs907094 (13.62±5.65, 15.54±4.66)( P<0.05). Additionally, significant differences were noted in the cognitive factor scores between AA and GA genotypes (17.76±5.58, 19.43±5.73)( P<0.05). Conclusions:In the Han population from northern Henan province, the rs907094 polymorphism of the PPP1R1B gene is associated with schizophrenia.And the specific locus may be implicated in arousal/hostility symptoms and cognitive dysfunction.

Objective:To evaluate the application effect of improved problem-based learning (PBL) based on 5W2H thinking in the course of "massage therapy".Methods:The undergraduate students in Class 1 and Class 2 of Acupuncture and Massage in the first semester of the 2023-2024 academic year at Heilongjiang University of Chinese Medicine were selected as the research subjects. The "massage therapy" was taught in Class 1 with the traditional method (control group, n=66) and in Class 2 with the method of improved PBL with 5W2H thinking (observation group, n=68). The two groups of students were compared in terms of theoretical knowledge of massage therapy, the assessment of massage skills, comprehensive ability, innovation ability, and practical ability, as well as the procedural evaluation indicators of massage. SPSS 25.0 was used for normality test and t test χ2 test. Results:After the completion of the study, the observation group showed higher scores in theoretical knowledge (90.56±11.73), massage skill proficiency [(87.22±11.57) vs. (78.23±9.45)], massage skill demonstration [(84.56±11.20) vs. (74.69±9.13)], mannequin usage [(82.98±10.75) vs. (72.66±8.89)], and massage skill mechanics [(86.38±11.45) vs. (73.35±8.94)] compared to the control group. The observation group also outperformed the control group in medical humanities [(85.53±10.64) vs. (64.86±7.33)], teacher-student and student-student interaction [(85.35±8.67) vs. (80.15±7.46)], clinical thinking and operation [(90.05±12.13) vs. (74.26±8.94)], and team coordination and cooperation [(85.60±10.06) vs. (81.53±9.33)]. In addition, the observation group scored higher than the control group in learning participation rate [(18.20±3.75) vs. (13.15±2.93)], error correction rate [(27.56±5.85) vs. (22.11±4.62)], operational stability [(48.43±7.79) vs. (42.06±6.60)], and total score [(94.19±7.56) vs. (77.32±6.78)].Conclusions:The application of improved PBL based on 5W2H thinking in the course of "massage therapy" has significant clinical implications. It can not only improve the teaching quality and effect, but also cultivate students' clinical thinking, teamwork, learning interest, and innovation ability, making it suitable for further promotion and application.