Objective To develop a questionnaire for measuring the legal legitimacy of occupational health managers among enterprises, and to evaluate its reliability and validity. Methods Based on the theory of subjective procedural justice, an item pool for the Questionnaire on the Legal Legitimacy of Enterprise Occupational Health Managers was constructed through literature review and policy screening, database collation, and expert interviews. The Delphi method was used to conduct two rounds of expert consultation with 37 experts, and the questionnaire item pool was adjusted and refined based on the experts' opinions to determine the final version of the questionnaire. A total of 317 occupational health managers were selected using a random number table method to complete the questionnaire survey. The data were then used to evaluate its reliability and validity. Results The questionnaire response rates for the two rounds of expert consultation were 94.6% and 100.0%, respectively. The expert authority coefficient was 0.82, and Kendall's W coefficients of concordance were 0.16 and 0.23, respectively (both P<0.001). The final version of Questionnaire on the Legal Legitimacy of Enterprise Occupational Health Managers consists of four dimensions (legal statement, law enforcement, social environment, and obligation to comply with the law) with a total of 21 items. The Cronbach's α coefficients for the overall questionnaire and its four dimensions were 0.96, 0.97, 0.98, 0.70, and 0.91, respectively (all >0.70). The corrected item-total correlation for each item was >0.50. The results of confirmatory factor analysis indicated that all fit indices met good fit standards: 􀱽 ²/df ratio = 2.85, goodness-of-fit index = 0.917, adjusted goodness-of-fit index = 0.905, comparative fit index = 0.933, Tucker-Lewis index = 0.909, root mean square error of approximation = 0.056, and standardized root mean square residual = 0.059. The composite reliabilities for the four dimensions were 0.97, 0.98, 0.63, and 0.89, respectively. The average variance extracted values were 0.73, 0.91, 0.45, and 0.73, respectively. Conclusion The newly developed Questionnaire on the Legal Legitimacy of Enterprise Occupational Health Managers demonstrates good reliability and validity, with strong scientific rigor and robustness. It can be used as a measurement tool for assessing the legal legitimacy of occupational disease prevention and control laws and regulations among enterprise occupational health managers.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

ObjectiveTo investigate the incidence of postherpetic neuralgia （PHN） and its associated risk factors in patients aged ≥50 years with herpes zoster （HZ） who received standard antiviral therapy at the dermatology outpatient clinic of our center. MethodsHZ patients were identified by searching the medical record system using "herpes zoster" as the keyword， and those diagnosed between July 2020 and July 2021. Patients meeting the inclusion criteria were followed up via telephone to retrospectively assess the occurrence of PHN. Patients were divided into a PHN group and a non-PHN group based on the presence of PHN. General patient information （gender， age， and underlying diseases）， prodromal pain intensity， and lesion characteristics （area， location， and acute-phase pain intensity） as well as treatment modalities （pharmacotherapy， physical therapy， and combined analgesic therapy） were compared between the two groups. Intergroup comparisons and multifactorial analyses were performed to identify factors associated with the development of PHN in HZ patients. Pain intensity was assessed using the Numerical Rating Scale （NRS） for PHN pain， acute-phase HZ pain， and prodromal pain. Intergroup comparisons were conducted using the chi-square test， Mann-Whitney U test， and t-test. Binary logistic regression was used for multivariate analysis to identify independent risk factors. ResultsA total of 238 HZ patients aged ≥50 years who received standard antiviral therapy were ultimately included， of whom 76 （31.9%） developed PHN. Unifactorial analysis showed that age， lesion area， acute-phase pain intensity， and the use of gabapentin or combined analgesic therapy significantly influenced the occurrence of PHN after HZ （P<0.05）. Statistically significant indicators （P<0.05） from the unifactorial analysis and the different analgesic regimens adopted by patients were included in the multifactorial analysis. Multifactorial analysis revealed that lesion area ≥1% （OR=2.501； 95%CI=1.408-4.443； P=0.002<0.05） and acute-phase pain score （OR=1.160； 95%CI=1.028-1.309； P=0.016<0.05） were independent risk factors for PHN. Age and the use of gabapentin or combined analgesic therapy showed no statistically significant association with the occurrence of PHN （P>0.05）. ConclusionsIn HZ patients aged ≥50 years receiving standard antiviral therapy， the incidence of PHN is 31.9%. A lesion area ≥1% and higher acute-phase pain NRS scores are identified as independent risk factors for the development of PHN in these patients.

ObjectiveThis study aimed to elucidate the specific molecular mechanism by which PAGE5 promotes breast cancer cell invasion and hepatic metastasis through regulating the PI3K/AKT signaling pathway and its downstream effector， matrix metalloproteinase 1 （MMP1）. MethodsBioinformatics analysis using the TCGA database was performed to evaluate PAGE5 expression in metastatic breast cancer tissues. The effects of PAGE5 on the proliferation， migration， and invasion capabilities of breast cancer cells were analyzed using CCK-8， EdU， Transwell， and wound healing assays. A splenic injection hepatic metastasis model in NOD-SCID mice was employed to validate the impact of PAGE5 on breast cancer liver metastasis. Transcriptome sequencing and KEGG enrichment analysis were conducted to identify potential signaling pathways regulated by PAGE5. Western blot was used to detect AKT phosphorylation levels. Quantitative real-time polymerase chain reaction （qPCR） was applied to screen and validate downstream target molecules of PAGE5. ResultsBioinformatic analysis revealed that PAGE5 expression was significantly upregulated in distant metastasis of breast cancer. Both in vitro and in vivo experiments confirmed that PAGE5 overexpression markedly enhanced the migration and invasion abilities of breast cancer cells and promoted the formation of liver metastatic lesions， whereas PAGE5 knockdown suppressed breast cancer liver metastasis （P＜0.000 1）. Transcriptome sequencing and KEGG enrichment analysis indicated that PAGE5 significantly activated the PI3K-AKT signaling pathway （P=0.028 5）. Western blot confirmed that PAGE5 upregulated p-AKT levels， which could be reversed by MK2206. The qPCR results confirmed that MMP1 is a key downstream effector of PAGE5， and its expression can be inhibited by MK2206 （P＜0.000 1）. ConclusionsThis study preliminarily demonstrates that PAGE5 can activate the PI3K/AKT signaling pathway and mediate the invasion and liver metastasis of breast cancer through MMP1.

ObjectiveTo investigate the incidence of postherpetic neuralgia （PHN） and its associated risk factors in patients aged ≥50 years with herpes zoster （HZ） who received standard antiviral therapy at the dermatology outpatient clinic of our center. MethodsHZ patients were identified by searching the medical record system using "herpes zoster" as the keyword， and those diagnosed between July 2020 and July 2021. Patients meeting the inclusion criteria were followed up via telephone to retrospectively assess the occurrence of PHN. Patients were divided into a PHN group and a non-PHN group based on the presence of PHN. General patient information （gender， age， and underlying diseases）， prodromal pain intensity， and lesion characteristics （area， location， and acute-phase pain intensity） as well as treatment modalities （pharmacotherapy， physical therapy， and combined analgesic therapy） were compared between the two groups. Intergroup comparisons and multifactorial analyses were performed to identify factors associated with the development of PHN in HZ patients. Pain intensity was assessed using the Numerical Rating Scale （NRS） for PHN pain， acute-phase HZ pain， and prodromal pain. Intergroup comparisons were conducted using the chi-square test， Mann-Whitney U test， and t-test. Binary logistic regression was used for multivariate analysis to identify independent risk factors. ResultsA total of 238 HZ patients aged ≥50 years who received standard antiviral therapy were ultimately included， of whom 76 （31.9%） developed PHN. Unifactorial analysis showed that age， lesion area， acute-phase pain intensity， and the use of gabapentin or combined analgesic therapy significantly influenced the occurrence of PHN after HZ （P<0.05）. Statistically significant indicators （P<0.05） from the unifactorial analysis and the different analgesic regimens adopted by patients were included in the multifactorial analysis. Multifactorial analysis revealed that lesion area ≥1% （OR=2.501； 95%CI=1.408-4.443； P=0.002<0.05） and acute-phase pain score （OR=1.160； 95%CI=1.028-1.309； P=0.016<0.05） were independent risk factors for PHN. Age and the use of gabapentin or combined analgesic therapy showed no statistically significant association with the occurrence of PHN （P>0.05）. ConclusionsIn HZ patients aged ≥50 years receiving standard antiviral therapy， the incidence of PHN is 31.9%. A lesion area ≥1% and higher acute-phase pain NRS scores are identified as independent risk factors for the development of PHN in these patients.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

OBJECTIVE To investigate the improvement mechanism of hyperoside （HYP） on non-alcoholic fatty liver disease （NAFLD）. METHODS Male C57BL/6 mice were randomly divided into normal （NFD） group， model （HFD） group and HYP group， with 8 mice in each group. Except for NFD group， the mice in other groups were fed with HF60 high-fat diet to establish NAFLD model； HYP group was simultaneously given HYP 100 mg/kg intragastrically every day， for 16 consecutive weeks. The body weight and liver weight of mice in each group were recorded 16 h after the last medication； the histopathological changes and lipid accumulation in the liver were observed， and the contents of triglyceride （TAG） in liver tissue and serum contents of TAG， aspartate transaminase （AST） and alanine transaminase （ALT） were measured； LC-MS/MS method was adopted to detect lipid changes in the liver tissue of mice for lipidomics analysis， and protein expressions of lipid synthesis-associated proteins peroxisome proliferator-activated receptor α （PPARα） were also tested. Human hepatocellular carcinoma cell line HepG2 was divided into normal control group， model group， HYP low-concentration group （50 μmol/L）， HYP high-concentration group （100 μmol/L）， HYP low-concentration+GW6471 （PPARαinhibitor） group， and HYP high-concentration+GW6471 group. Except for normal control group， the remaining cells were induced with oleic acid and palmitic acid to establish a high-fat cell model. The accumulation of lipid droplets in each group of cells was observed， and the TAG content was detected. RESULTS Compared with HFD group， HYP group exhibited significant reductions in liver fat vacuoles， lipid accumulation， liver weight， and TAG content in liver tissue， as well as serum contents of ALT， AST and TAG （P＜0.05）. Additionally， the expression of PPARα protein in liver tissue was significantly increased （P＜0.05）， and the pathological morphological changes associated with NAFLD were alleviated. Lipidomic analysis revealed that HYP significantly reduced the levels of TAG， diacylglycerol and other lipids in the liver. Compared with model group， cellular lipid droplet accumulation and TAG content decreased significantly in HYP low- and high-concentration groups （P＜0.05）； GW6471 could significantly reverse the improvement effect of HYP on above indicators （P＜0.05）. CONCLUSIONS HYP can effectively ameliorate NAFLD induced by a high-fat diet in mice， and the mechanism may be related to the activation of PPARα to regulate hepatic lipid synthesis.

Objective: To investigate the iodine nutrition status of children aged 8-10 in Guangming, Longhua and Yantian District of Shenzhen in 2023, and to explore the influencing factors of thyroid volume. To evaluate prevention strategies and to provide a scientific basis for the elimination of iodine deficiency disorders. Methods: Urine and household salt samples were randomly collected from 580 non-boarding students aged 8-10 years foriodine content detection. Thyroid volume was measured using a fully digital ultrasound imaging system, and goiter prevalence was calculated. Results: A total of 580 samples was tested. The median salt iodine concentration was 23.86 mg/kg, with 93.62% qualified iodized salt and 94.48% coverage rate. The median of urinary iodine was 265.00 μg/L, mainly distributed between 200 - < 300 μg/L and ≥300 μg/L. The proportion of children with ap⁃ propriate iodine was 20. 86% , and the proportion of children with insufficient or excessive urinary iodine levels was 10. 86% and 68. 28% of the total surveyed population , respectively. The median thyroid volume was 3. 27 mL , and the goiter rate was 1. 72% . Multiple linear regression analysis showed that age was the risk factor for thyroid volume (8=0 328, P<0.05). while urinary iodine was the protective factor for thyroid volume(B=-4.134x10-4,P<0.05). Conclusion The qualified iodized salt rate, median of urinary iodine,and goiter prevalence of 580 children aged 8 - 10 meet the elimination criteria for iodine deficiency disorders. Age and urinary iodine are closely related to thyroid volume change. The urinary iodine level of children is generally high and requires serious attention.

Objective:To explore the correlation between serum soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and cognitive impairment in patients with cerebral small vessel disease (CSVD), and the role of deep medullary vein (DMV) score in this process.Methods:A total of 140 patients with CSVD admitted to the Department of Neurology, the First Affiliated Hospital of Henan Medical University from December 2022 to August 2024 were selected as the research objects. The basic data statistics, head magnetic resonance imaging examination, cognitive function assessment, serum sTREM2 detection and DMV score were performed. All data were analyzed by SPSS 29.0 software and GraphPad Prism 10.0 software packages. Logistic regression model was used to explore the influencing factors of cognitive impairment. Structural equation model was used to analyze the mediating effect of DMV score on the association between serum sTREM2 and cognitive impairment. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum sTREM2 level and DMV score for cognitive impairment in CSVD patients.Results:Serum sTREM2 level ( B=0.017, OR=1.017, 95% CI=1.003-1.031), DMV score ( B=0.375, OR=1.455, 95% CI=1.175-1.802) and years of education ( B=-0.248, OR=0.780, 95% CI=0.635-0.958) were risk factors for cognitive impairment (all P<0.05). sTREM2 not only directly affected cognitive function, but also indirectly affected cognitive function through DMV score. The direct effect (effect size=-0.022) and mediating effect (effect size=-0.007) accounted for 75.9% and 24.1% of the total effect (effect size=-0.029), respectively. The areas under the ROC curve of serum sTREM2 level, DMV score, and their combination for predicting cognitive impairment in CSVD patients were 0.880, 0.891, and 0.910, respectively (all P<0.001). Conclusion:Serum sTREM2 not only directly affects the cognitive function of patients with cerebral small vessel disease, but also indirectly affects cognitive function through DMV score. The combination of serum sTREM2 levels and DMV score has high predictive value for the risk of CSVD-related cognitive impairment.

Objective:To analyze policy differences in general outpatient fund pooling of employee basic medical insurance in Yangtze River Delta Region and raise suggestions from the perspective of coordinated development.Methods:The study analyzed policy documents on general outpatients financing,outpatient chronic and special diseases,and inclusion of retail pharmacies into risk pooling at provincial level and in some economically developed cities before August,2024.Typical cases were selected for detailed introduction.Results:General outpatient coverage of employee medical insurance in Yangtze River Delta Region is high,with individual account payment scenarios expanding to commercial health insurance,Long Term Care Insurance and family physician contracted service fees.Number of outpatient chronic and special diseases ranges from 3 to 83.Retail pharmacy policies differ less in access conditions and treatment and e-prescription is advancing rapidly.Suzhou is actively exploring total budget management of retail pharmacies.Conclusions:Outpatient fund pooling policies should be gradually promoted under the principle of"differentiated coordination".It is necessary to transform outpatient chronic and special diseases from"disease coverage"to"cost coverage";strengthen the management of retail pharmacies under the outpatient fund pooling scheme,and improve the coordinated regulatory mechanism for direct settlement of outpatient and medication expenses incurred in other places in the Yangtze River Delta.