Objective:To explore the relationship between obesity indicators and DNA methylation clocks acceleration,and to analyze their temporal sequence.Methods:Data were obtained from two sur-veys conducted in 2013 and 2017-2018 by the Chinese National Twin Registry.Peripheral blood DNA methylation data were measured using the Illumina Infinium Human Methylation 450K BeadChip and EPIC BeadChip.DNA methylation clocks/acceleration metrics(GrimAA,PCGrimAA and Dunedin-PACE)were calculated using the DNA methylation online tool(https://dnamage.genetics.ucla.edu/)or R code provided by researchers.Obesity indicators included weight,body mass index(BMI),waist circumference,waist-hip ratio,and waist-height ratio.A total of 1 070 twin individuals were included in the cross-sectional analysis,comprising 378 monozygotic(MZ)twin pairs and 155 dizygotic(DZ)twin pairs for within-pair analysis.Mixed-effects models were used to examine the associations between obesity indicators and DNA methylation clocks,as well as their acceleration measures.The longitudinal analysis included 314 twin individuals,comprising 95 MZ twin pairs and 62 DZ twin pairs for within-pair analy-sis.Cross-lagged panel models were applied to further explore the temporal relationships between obesity and DNA methylation clock indicators.All analyses were conducted both in the full twin sample and separately within MZ and DZ twin pairs.Results:In the cross-sectional analysis population,monozygotic twins accounted for 71.0％,males for 68.0％,and the mean chronological age was(49.9±12.1)years.In the longitudinal analysis population,monozygotic twins accounted for 60.5％,males for 60.8％,with a mean baseline chronological age of(50.4±10.2)years and a mean follow-up duration of(4.6±0.6)years.Except for the waist-to-hip ratio,which was significantly higher at follow-up com-pared with baseline,no statistically significant differences were observed in the means of other obesity in-dicators between baseline and follow-up.Correlation analysis revealed that weight,BMI,waist circumfe-rence,waist-hip ratio(WHR),and waist-height ratio(WHtR)were positively correlated with Dunedin-PACE in all the twins,with WHtR showing the strongest association(β=0.21,95％CI:0.11 to 0.31).Weight and BMI were negatively associated with GrimAA(β=-0.03,95％CI:-0.05 to-0.01;β=-0.07,95％CI:-0.12 to-0.02),while weight was negatively associated with PCGrim-AA(β=-0.02,95％CI:-0.03 to 0.00).However,within-twin-pair analyses showed no statistically significant correlations.Cross-lagged panel model analysis indicated that higher baseline weight might lead to increased GrimAA at follow-up,while elevated baseline weight,BMI,and waist circumference might increase PCGrimAA.Higher baseline WHR was associated with increased DunedinPACE at follow-up.Conclusion:Obesity indicators correlate with DNA methylation clock acceleration metrics.Baseline obesity may influence changes in certain DNA methylation clock indicators over time,suggesting that obesity could exert long-term health effects by accelerating DNA methylation aging.However,these associations may be confounded by shared genetic or environmental factors among the twins.

Objective:To analyze the clinical features, imaging features and diagnosis and treatment process of a female pelvic epithelioid inflammatory myofibroblastic sarcoma (EIMS) with peritoneal metastasis, so as to improve the clinical understanding and diagnostic ability of the disease and avoid misdiagnosis and missed diagnosis.Methods:The clinical data of a female patient with pelvic EIMS combined with peritoneal metastasis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:The triad examination of the patient involved an irregular solid mass in the pelvic cavity about 8.0 cm×9.0 cm in size. Laboratory examination revealed human epididymal protein 4(HE4)154.00 pmol/L. The ultrasonography showed multiple low-echo masses in deep pelvic cavity with unclear boundary and uneven internal echo, and color doppler flow imaging (CDFI) showed abundant internal blood flow signals. Enhanced CT showed uneven and obvious enhancement of the lesion. Pathological examination showed the infiltration of inflammatory cells in the mucous interstitial background. The tumor cells were round and epithelioid, with large nuclei, deep staining and obvious nucleolus. Immunohistochemistry showed anaplastic lymphoma kinase (ALK) positive, and molecular pathology fluorescence in situ hybridization showed ALK gene amplification (positive). Combined with pathological, immunohistochemical and genetic tests, EIMS was diagnosed. Conclusions:EIMS should be considered when there are single or multiple solid or cystic nodules or masses in the pelvic cavity with obvious enhancement, invasive growth and peritoneal implantation metastasis, and the correct diagnosis can be made according to the pathological findings, immunohistochemistry and genetic test results.

Objective:To investigate the prognosis of postoperative adjuvant therapy for hepatocellular carcinoma after conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 103 patients with initially unresectable hepatocellular carcinoma (HCC) who were admitted to 11 medical centers in China, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from November 2019 to May 2023 were collected. There were 83 males and 20 females, aged (54±12)years. All 103 patients underwent conversion therapy of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) successfully followed by sequential hepatectomy, of which 72 patients undergoing postoperative adjuvant therapy were divided into the adjuvant therapy group, and 31 patients undergoing postoperative follow-up monitoring were divided into the follow-up monitoring group. Observation indicators: (1) follow-up and postoperative condi-tions; (2) analysis of factors influencing recurrence-free survival time of patients; (3) stratified ana-lysis. Comparison of count data between group was conducted using the chi-square test or Fisher exact probability. The R software was used to draw survival curves, and the Log-rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the Cox proportional hazard model. Results:(1) Follow-up and postoperative conditions. All 103 patients were followed up for 21.0(range, 1.9?47.2)months, with the median recurrence-free survival time of 28.7 months and the 1-, 2-, 3-year recurrence-free survival rates of 68.6%, 55.6%, 41.2%. The median overall survival time of 103 patients was unreached, and the 1-, 2-, 3-year overall survival rates were 90.9%, 82.1%, 69.6%, respectively. The median recurrence-free survival time was 33.1 months in patients of the adjuvant therapy group, with the 1-, 2-year recurrence-free survival rates as 77.2%, 61.5%. The median recurrence-free survival time was 11.1 months in patients of the follow-up monitoring group, with the 1-, 2-year recurrence-free survival rates as 46.6%, 40.8%. There was a significant difference in recurrence-free survival between the two groups of patients ( χ2=5.492, P<0.05). (2) Analysis of factors influencing recurrence-free survival time of patients. Results of multivariate analy-sis showed that pathologic complete response and postoperative adjuvant therapy were independent factors influencing recurrence-free survival time of HCC patients undergoing conversion therapy of combined targeted therapy and immunotherapy followed by sequential hepatectomy ( hazard ratio=0.297, 0.492, 95% confidence interval as 0.137?0.647, 0.268?0.903, P<0.05). (3) Stratified analysis. Of the 71 patients with non-pathologic complete response, the median recurrence-free survival time of 48 patients in the adjuvant therapy group was 24.0 months, with the 1-, 2-year recurrence-free survival rates as 67.4%, 48.8%. The median recurrence-free survival time of 23 patients with non-pathological complete response in the follow-up monitoring group was 7.4 months, with the 1-, 2-year recurrence-free survival rates as 35.0%, 26.3%. There was a significant difference in recurrence-free survival between the 48 patients with non-pathologic complete response in the adjuvant therapy group and the 23 patients with non-pathologic complete response in the follow-up monitoring group ( χ2=5.241, P<0.05). Conclusion:For HCC patients with conversion therapy of TKIs and ICIs followed by sequential hepatectomy, postoperative adjuvant therapy, compared to postoperative follow-up monitoring, can prolong the recurrence-free survival time of patients, of whom cases with non-pathologic complete response can benefit from adjuvant therapy.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

Objective:To explore the necessity and basic connotation of building an integrated eye health service system and propose a systematic const ruction pathway.Methods:A multi-dimensional analytical framework for an integrated eye health service system was constructed using literature review,interviews,and the rainbow model theory.Results:Considering the current state of eye disease prevention and control in China,along with the practical need to address the imbalance in the supply and demand structure of ophthalmic resources,it is necessary to build an integrated eye health service system that is fair,accessible,systematic,continuous,high-quality and efficient.Conclusion:It is needed to further improve the top-level design framework,enhance system integration,consolidate the service network at the grassroots level,strengthen organizational coordination,establish specialized eye health prevention and treatment centers,promote professional collaboration,deliver integrated and proactive service models,optimize service integration,and reinforce enabling factors through functional unification and standardized protocols.

Objective To translate the good death inventory-short form(GDI-SF)into Chinese and test its reliability and validity among bereaved family members of cancer patients.Methods A Chinese version of GDI-SF was created through translation,reconciliation,back translation,expert panel review and pilot testing.Then the inventory was administered to 699 bereaved family members of cancer patients recruited by convenience sampling.Reliability and validity were assessed.Results Toally 305 family members finished the study.The item-level content validity index(I-CVI)and average content validity index(S-CVI/Ave)were both 1.00.Exploratory factor analysis yielded 5 common factors:professional medical care(6 items),preparation for farewell(4 items),dignity and life value(4 items),natural death and moral support(2 items),and physical and mental comfort(2 items).These factors explained 52.176%of total variance.Overall Cronbach α coefficient of the Chinese version GDI-S was 0.779,and split-half reliability was 0.731.The Pearson correlation coefficient range between the score of each item of the Chinese version of GDI-SF and the score of its corresponding dimension was 0.591 to 0.769(P<0.01).Conclusion The Chinese version GDI-SF exhibits acceptable reliability and validity assessment of the quality of good dying in cancer patients from the perspective of bereaved family members.

Objective:To analyze the clinical features, imaging features and diagnosis and treatment process of a female pelvic epithelioid inflammatory myofibroblastic sarcoma (EIMS) with peritoneal metastasis, so as to improve the clinical understanding and diagnostic ability of the disease and avoid misdiagnosis and missed diagnosis.Methods:The clinical data of a female patient with pelvic EIMS combined with peritoneal metastasis in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.Results:The triad examination of the patient involved an irregular solid mass in the pelvic cavity about 8.0 cm×9.0 cm in size. Laboratory examination revealed human epididymal protein 4(HE4)154.00 pmol/L. The ultrasonography showed multiple low-echo masses in deep pelvic cavity with unclear boundary and uneven internal echo, and color doppler flow imaging (CDFI) showed abundant internal blood flow signals. Enhanced CT showed uneven and obvious enhancement of the lesion. Pathological examination showed the infiltration of inflammatory cells in the mucous interstitial background. The tumor cells were round and epithelioid, with large nuclei, deep staining and obvious nucleolus. Immunohistochemistry showed anaplastic lymphoma kinase (ALK) positive, and molecular pathology fluorescence in situ hybridization showed ALK gene amplification (positive). Combined with pathological, immunohistochemical and genetic tests, EIMS was diagnosed. Conclusions:EIMS should be considered when there are single or multiple solid or cystic nodules or masses in the pelvic cavity with obvious enhancement, invasive growth and peritoneal implantation metastasis, and the correct diagnosis can be made according to the pathological findings, immunohistochemistry and genetic test results.

BACKGROUND:It is urgent to improve the study on the molecular mechanism of Ban's Culuan Zhuyun Decoction improving oocyte quality in polycystic ovary syndrome.OBJECTIVE:To observe the effects of Ban's Culuan Zhuyun Decoction on oocyte quality in a mouse model of polycystic ovary syndrome and to explore the underlying mechanisms of its intervention in polycystic ovary syndrome.METHODS:Subcutaneous injection of dehydroepiandrosterone sulfate was used to establish the polycystic ovary syndrome model in 21-day-old female Kunming mice,and the treatment was conducted for 21 consecutive days.The estrous cycle and pregnancy was recorded.ELISA was used to detect serum sex hormone levels.The rate of apoptosis in oocytes was detected using Annexin V staining.The level of reactive oxygen species in oocytes was detected using dichlorodihydrofluorescein diacetate.The condition of spindle bodies and chromosomes in oocytes were detected using the immunofluorescence method.Network pharmacology and molecular docking were used to verify the binding properties of Ban's Culuan Zhuyun Decoction core active components and oocyte maturation-related factors(growth differentiation factor 9 and bone morphogenetic protein 15).Real-time fluorescence quantitative PCR and western blot were used to detect the mRNA and protein expression levels of growth differentiation factor 9 and bone morphogenetic protein 15 in oocytes,respectively.RESULTS AND CONCLUSION:(1)Ban's Culuan Zhuyun Decoction core active components(quercetin,kaempferol,and β-sitosterol)showed good binding activities with growth differentiation factor 9 and bone morphogenetic protein 15.(2)Ban's Culuan Zhuyun Decoction ameliorated the estrous cycle,regulated serum hormone,increased the pregnancy,decreased the rate of apoptosis,declined the level of reactive oxygen species,diminished the rate of abnormal spindle assembly and chromosome loss(P<0.01,P<0.05);and promoted the mRNA and protein expression of growth differentiation factor 9 and bone morphogenetic protein 15(P<0.05).Therefore,Ban's Culuan Zhuyun Decoction may improve the oocyte quality and increase the fertility of polycystic ovary syndrome mice by regulating the gene expression of growth differentiation factor 9 and bone morphogenetic protein 15.

Objective To investigate the microstructural changes of white matter in patients with relapsing-remitting multiple sclerosis(RRMS)and its correlation with clinical functional scores.Methods A total of 20 patients with RRMS(RRMS group)and 20 healthy controls(HC)(HC group)were selected and underwent diffusion tensor imaging(DTI)and expanded disability status scale(EDSS)scores.Patients with RRMS were categorized into two groups based on their EDSS scores,including MS-1 group(motor dysfunction with visual impairment)and MS-2 group(motor dysfunction).Image processing was performed via tract-based spatial statistics(TBSS).Group comparisons were executed using the t-test,while correlations were analyzed utilizing Spearman correlation.Results In the RRMS group,reduced fractional anisotropy(FA)values were accompanied by increased mean diffusivity(MD)and radial diffusivity(RD)values in the forceps major,forceps minor,bilateral cingulum,bilateral uncinate fasciculus,bilateral superior longitudinal fasciculus,bilateral inferior longitudinal fasciculus,bilateral inferior fronto-occipital fasciculus,bilateral corticospinal tract and bilateral anterior thalamic radiation compared with the HC group.Additionally,In the RRMS group,increased axial diffusivity(AD)values were noted in the forceps major,forceps minor,bilateral superior longitudinal fasciculus(temporal),right inferior fronto-occipital fasciculus,bilateral corticospinal tract and right anterior thalamic radiation compared with the HC group.Compared with the MS-2 group,the MS-1 group exhibited higher FA values in the right cingulum(cingulate gyrus part)and higher AD values in the left cingulum(cingulate gyrus part).Correlation analysis revealed negative correlations between the FA values of the forceps major,right superior longitudinal fasciculus and the motor function scores in RRMS group.Conversely,positive correlations were identified between the MD values of the forceps minor,right superior longitudinal fasciculus,right inferior fronto-occipital fasciculus,left corticospinal tract and the RD values of the forceps minor,right cingulum(hip-pocampus),right superior longitudinal fasciculus,and left corticospinal tract,as well as the motor function scores.Conclusion RRMS patients exhibit microstructural damage in white matter and are associated with motor dysfunction,which provides imaging support for the pathological mechanisms underlying motor dysfunction in RRMS patients.

OBJECTIVE To observe the effect of the Chinese herbal compound Weidiao No.3 Formula(WD-3)combined with immunotherapy and chemotherapy on survival outcomes in patients with advanced non-small cell lung cancer(NSCLC)with lung-spleen qi dificiency type.METHODS A total of 216 patients with stage Ⅲb-Ⅳ NSCLC without driver gene mutations and with lung-spleen qi vacuity pattern and admitted to the oncology departments of Wuxi Hospital of Traditional Chinese Medicine and Jiangnan Uni-versity Affiliated Hospital between January 1,2020,and March 1,2025,were enrolled.Based on whether they received WD-3 oral treatment(≥3 months),they were divided into a Chinese medicine exposure group(n=98;WD-3+immunotherapy combined with chemo-therapy)and a non-exposure group(n=118;immunotherapy combined with chemotherapy alone).Propensity score matching(PSM)was used to balance baseline characteristics.Overall survival(OS),progression-free survival(PFS),and baseline characteristics were com-pared between the two groups.Cox proportional hazards regression model was used to analyze the association between exposure and outcome,and sensitivity analysis was performed.RESULTS After PSM,there were no statistically significant differences in baseline characteristics between the two groups(P>0.05).After matching,the median OS(32.92 months)and median PFS(9.07 months)in the Chinese medicine exposure group were longer than those in the non-exposure group(23.24 months and 7.89 months,respectively),with statistically significant differences(P<0.05).Multivariate analysis was conducted,incorporating age,PD-L1 expression,KPS score,pathological type,and other factors as covariates to assess the independent association between WD3 exposure and OS and PFS outcomes.The results indicated that WD3 exposure was statistically significant in reducing the risk of death(OS outcome)and disease progression(PFS outcome).Specifically,for the OS outcome,the HR was 0.626,with a 95%CI of 0.438 to 0.894,and P=0.01;for the PFS outcome,the HR was 0.721,with a 95%CI of 0.535 to 0.972,and P=0.032.Sensitivity analysis showed robust results(E-value>2.1).CONCLUSION WD-3 combined with immunotherapy and chemotherapy may prolong OS and PFS and reduce mortality risk in patients with advanced NSCLC without driver gene mutations and with lung-spleen qi dificiency type,achieves adequate therapeutic effects.