Objective: To investigate the current status of benefit finding among young and middle-aged patients with type 2 diabetes mellitus (T2DM) and analyze its influencing factors, so as to provide a reference for improving the level of benefit finding in this population. Methods: From November 2022 to May 2023, young and middle-aged patients with T2DM aged 18-59 years hospitalized in the endocrinology departments of 2 tertiary hospitals in Hengyang City, Hunan Province were selected as survey subjects by a convenience sampling method. Basic demographic information was collected using a general questionnaire survey. Benefit finding, resourcefulness, and stigma were evaluated using the Benefit Finding Scale, the Chinese Version of the Resourcefulness Scale, and the Type 2 Diabetes Stigma Assessment Scale, respectively. A multiple linear regression model was used to analyze the influencing factors of benefit finding among young and middle-aged patients with T2DM. Results: A total of 305 young and middle-aged patients with T2DM were investigated, including 222 males (72.79%) and 83 females (27.21%). There were 231 cases aged 45-59 years, accounting for 75.74%. The scores for benefit finding, resourcefulness, and stigma were (42.86±6.06), (75.12±11.30), and (41.20±10.10), respectively. Multiple linear regression analysis showed that young and middle-aged patients with T2DM who were male (β′=0.088), aged 18-<45 years (β′=0.083), absence of diabetes complications (β′=0.124), and had higher resourcefulness scores (β′=0.679) had higher levels of benefit finding, while patients with higher stigma scores (β′=-0.097) had lower levels of benefit finding. Conclusion The level of benefit finding among young and middle-aged patients with T2DM was moderate, and was related to gender, age, diabetes complications, resourcefulness, and stigma.

ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture （JDJM） in treating synovial lesions in knee osteoarthritis （KOA）. MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group （n=8） and a model group （n=35）. The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage， with a modeling period of 6 weeks， resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group， celecoxib group， JDJM group and JDJM+740Y-P group， each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg^-1， while the JDJM was administered a single dose of 6.8 mL·kg^-1 （4.515 2 g·kg^-1） of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway activator + JDJM group received 4.515 2 g·kg^-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg^-1 740Y-P. For a period of 6 weeks， the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period， the knee joint pain threshold and circumference were measured， and hematoxylin-eosin （HE） staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay （ELISA） measured the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-18） and tumor necrosis factor-α （TNF-α） in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， NOD-like receptor protein 3 （NLRP3）， cysteine-requiring aspartate protease-1 （Caspase-1） and gasdermin D （GSDMD） in the synovial tissues. Immunohistochemical （IHC） assay was performed to assess the protein expression of NLRP3， Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD. ResultsCompared to the blank group， the model group showed a significant increase in knee joint circumference and decrease in pain threshold， the synovial tissue pathology score was higher （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid significantly increased （P<0.01）. PI3K， Akt， mTOR phosphorylation as well as mRNA and protein expression increased （P<0.01）， while the mRNA and protein expression levels of NLRP3， Caspase-1 and GSDMD also significantly increased （P<0.01）. Compared to the model group， the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold， the synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid decreased （P<0.01）. The mRNA and protein expression of p-PI3K， p-Akt， p-mTOR， NLRP3， Caspase-1 and GSDMD were reduced （P<0.01）. Compared to the JDJM group， the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions， an increase in knee joint circumference， and a decrease in pain threshold. The synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid were higher （P<0.01）. The mRNA and protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD increased （P<0.01）. ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues， inhibiting pyroptosis， reducing inflammatory factor release， and protecting bony structures.

AIM: To evaluate the postoperative clinical efficacy of non-diffractive extended depth of focus intraocular lens(EDOF IOL)in patients with highly myopic cataract(HMC).METHODS:A retrospective analysis was conducted on the clinical data of patients diagnosed with HMC at the hospital from January 2022 to December 2024. Patients were divided into an observation group [undergoing femtosecond laser-assisted cataract surgery(FLACS)combined with non-diffractive EDOF IOL implantation] and a control group(undergoing FLACS combined with aspheric monofocal IOL implantation)according to the type of implanted IOL. Postoperative visual acuity(LogMAR), visual quality, and patient satisfaction were compared between the two groups.RESULTS: A total of 33 patients(47 eyes)were finally included in this study, including 10 patients(17 eyes)in the observation group and 23 patients(30 eyes)in the control group. The observation group had a median age of 59.0(52.8, 63.8)y, with 8 males(13 eyes)and 2 females(4 eyes). The control group had a median age of 56.0(53.5, 60.0)y, with 13 males(17 eyes)and 10 females(13 eyes). At 3 mo postoperatively, the best-corrected distance visual acuity(BCDVA)was 0.10(0.08, 0.12)in the observation group and 0.20(0.10, 0.40)in the control group(P=0.586). However, the best-corrected intermediate visual acuity(BCIVA)[0.10(0.10, 0.10)vs 0.50(0.40, 0.90), P=0.032] and best-corrected near visual acuity(BCNVA)[0.20(0.18, 0.20)vs 0.60(0.45, 1.45), P=0.044] in the observation group were significantly better than those in the control group. The defocus curve showed that the uncorrected visual acuity(UCVA)in the observation group was relatively stable within the range of -2.00 to +1.00 D, which was superior to that in the control group. Postoperative questionnaires showed that the spectacle independence rate(76%)and overall satisfaction(88%)in the observation group were significantly higher than those in the control group(10% and 60%, respectively).CONCLUSION: Non-diffractive EDOF IOL significantly improves intermediate and near visual acuity, reduces spectacle dependence, and maintains distance visual acuity by extending the depth of focus, providing better postoperative visual quality and life satisfaction for HMC patients.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Chronic heart failure （CHF）， as the terminal stage of various cardiovascular diseases， is characterized by a prolonged clinical course and recurrent exacerbations. The coexistence of CHF with anxiety and depression falls under the category of psycho-cardiological diseases. Studies have demonstrated that anxiety and depression are closely associated with adverse outcomes including elevated risks of cardiovascular events and increased mortality in CHF patients. The complex pathogenesis poses challenges to modern medical treatments， which often face limited efficacy and concurrent side effects. According to the theory of Shaoyang Pivot in traditional Chinese medicine （TCM）， this paper elucidates that obstructed Shaoyang Pivot—manifested as Qi transformation disorder， dysregulated fluid metabolism， and abnormal distribution of ministerial fire-serves as a critical pathological basis for CHF with anxiety and depression. Bupleuri Radix-based Formulas， such as Xiao Chaihu Tang， Chaihu Guizhi Tang， and Chaihu Jia Longgu Muli Tang， aim to harmonize lesser Yang to restore the Qi transformation， activate Yang to promote water excretion， and redistribute ministerial fire， thus effectively alleviating pathological states such as Qi stagnation， blood stasis， water retention， and phlegm-fire disturbing the heart in CHF patients with anxiety and depression. Consequently， they mitigate symptoms of this psycho-cardiological disease. Mechanism studies have revealed that Bupleuri Radix-based formulas exhibit multi-target effects， including modulation of neurotransmitters， suppression of inflammatory responses， regulation of lipid metabolism， protection of cardiomyocytes， and improvement of the endothelial function. By interpreting the TCM pathogenesis of CHF with anxiety and depression from the theory of Shaoyang Pivot， this paper delves into the therapeutic principles and mechanisms of Bupleuri Radix-based formulas， providing a theoretical foundation for optimizing TCM diagnosis and treatment strategies for psycho-cardiological diseases.

Objective: Previous studies have discovered a correlation between cigarette smoking and cortical thickness and surface area, but the causal relationship remains unclear. The objective of this investigation is to scrutinize the causal association between them. Methods: To derive summary statistics from a genome-wide association study (GWAS) on cortical thickness, surface area, and four smoking behaviors: 1) age of initiation of regular smoking (AgeSmk); 2) smoking initiation (SmkInit); 3) smoking cessation (SmkCes); 4) cigarettes per day (CigDay). Linkage disequilibrium score regression (LDSC) was employed to examine genetic association analysis. Furthermore, for traits with significant genetic associations, Mendelian randomization (MR) analyses were conducted. Results: The LDSC analysis revealed nominal genetic correlations between AgeSmk and right precentral surface area, left caudal anterior cingulate surface area, left cuneus surface area, left inferior parietal surface area, and right caudal anterior cingulate thickness, as well as between CigDay and left caudal middle frontal surface area, between SmkCes and left entorhinal thickness, and between SmkInit and left rostral anterior cingulate surface area, right rostral anterior cingulate thickness, and right superior frontal thickness (rg=-0.36–0.29, p<0.05). MR analysis showed a unidirectional causal association between left caudal middle frontal surface area and CigDay (βIVW=0.056, pBonferroni=2×10-4). Conclusion Left caudal middle frontal surface area has the potential to serve as a significant predictor of smoking behavior.

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

BackgroundSleep disorder in the first trimester is a fairly common health problem， and previous studies have mainly reflected the overall sleep quality through scale assessments， which may not accurately capture the differences among various subtypes. ObjectiveTo explore the latent profiles of sleep quality in first-trimester pregnant women and identify the physiological， psychological and social factors， in order to provide practical references for the development of personalized interventions for sleep disorders in first-trimester pregnant women. MethodsA total of 1 066 first-trimester pregnant women who visited the obstetric outpatient clinic of a tertiary A hospital in Shenzhen from October 2021 to October 2022 were investigated using the general information questionnaire， Pittsburgh Sleep Quality Index （PSQI）， Edinburgh Postnatal Depression Scale （EPDS）， Chinese version of short International Physical Activity Questionnaire （IPAQ-S-C） and Social Capital Assessment Tool in Pregnancy for Maternal Health （SCAT-MH）. Then the sleep profiles were identified through latent profile analysis， and the robust mixture regression model was employed to determine the influencing factors of sleep profiles. ResultsA 3-profile solution showed the best fit： 732 cases （68.67%） of good sleep quality group， 87 cases （8.16%） of low sleep efficiency group， and 247 cases （23.17%） of daytime dysfunction group. In comparison with subjects in good sleep quality group， first-trimester pregnant women in low sleep efficiency group were at a younger age （OR=0.951， 95% CI： 0.922~0.980）， held a Bachelor's degree or above （OR=1.869， 95% CI： 1.260~2.773） and exhibited lower levels of social capital （OR=0.962， 95% CI： 0.951~0.973）， while those in daytime dysfunction group were at an older age （OR=1.072， 95% CI： 1.027~1.120） and had higher levels of depression （OR=1.166， 95% CI： 1.115~1.218）. Pregnant women who were workers （OR=0.507， 95% CI： 0.293~0.876） were less likely to report daytime dysfunction. ConclusionThree latent profiles with significant heterogeneity are derived from the sleep quality of first-trimester pregnant women， and levels of depression and social capital are the main influencing factors of sleep quality. ［Funded by Industry-University-Research Innovation Fund for Chinese Universities （number， 2023HT018）］

Background/Aims: Growing evidence suggests histologic healing (HH) improves clinical outcomes in ulcerative colitis (UC) patients beyond endoscopic healing (EH). We hypothesize that HH is associated with better clinical outcomes in Asian UC patients, for whom data is lacking. Methods: We performed a retrospective study of UC patients in clinical remission (CR) with a follow-up colonoscopy and minimum 1-year follow-up post-colonoscopy. Primary outcome was clinical relapse (CRL), defined as either a Simple Clinical Colitis Activity Index score of > 2, medication escalation, hospitalization or colectomy. Predictors of CRL and HH were assessed. Results: One hundred patients were included with a median follow-up of 22 months. At index colonoscopy, 80 patients were in EH. On follow-up, 41 patients experienced CRL. Of 80 patients in EH, 34 (42.5%) had persistent histologic activity (Nancy Index ≥ 2) and 29 (36.3%) relapsed during the follow-up period. Amongst patients in CR and EH, those with HH had lower CRL rate (26.1% vs. 50.0%, P= 0.028) and longer CRL-free survival (mean 46.1 months vs. 31.5 months, P= 0.015) than those with persistent histologic activity. On bivariable analysis of 100 patients in CR, HH, and Mayo endoscopic score (MES) of 0 were significantly associated with lower risk of CRL. On multivariable analysis, only MES 0 remained predictive of lower CRL risk. Conclusions Above and beyond CR and EH, achieving HH improves clinical outcomes in Asian UC patients. However, HH may not confer incremental benefit if MES 0 has been achieved. Further prospective studies evaluating the benefit of histologically guided therapeutic decisions are needed.