Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

[Objective] To evaluate the clinical application value of intrauterine perfusion with platelet-rich plasma (PRP) combined with in vitro fertilization-frozen-thawed embryo transfer (IVF-FET) in patients with chronic endometritis (CE). [Methods] A randomized controlled trial (RCT) was conducted, enrolling 60 CE patients undergoing artificial cycle frozen embryo transfer at our hospital from January 2022 to January 2024. Participants were randomly divided into three groups: Group A (routine frozen embryo transfer, n=20), Group B (routine frozen embryo transfer + one PRP intrauterine perfusion, n=20), and Group C (routine frozen embryo transfer + two PRP intrauterine perfusions, n=20). Endometrial thickness during the transformation and transplantation phases, uterine artery pulsatility index (PI), resistance index (RI), systolic peak velocity/end-diastolic velocity (S/D) ratio during transplantation, serum levels of IL-2, IL-4, IL-6, IL-10, and TNF-α during transplantation, as well as biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and early miscarriage rate were compared across groups. [Results] No significant differences in endometrial thickness were observed among the three groups during the transformation phase (P>0.05). During the transplantation phase, endometrial thickness in Groups C and B was significantly higher than in Group A[9.54 (8.96-10.22) and 8.90 (8.34-9.72) vs 8.37 (7.89-8.75) mm, P<0.05], with Group C showing greater thickness than Group B (Z=3.733, P<0.05). Endometrial thickness in Groups C and B during transplantation was significantly increased compared to their respective transformation phases (Z=2.191, 2.462; P<0.05). Groups C and B exhibited lower PI, RI, and S/D values than Group A[PI:1.87 (1.77-1.97), 1.94 (1.88-2.15) vs 2.43 (2.35-2.49); RI:0.75 (0.73-0.77), 0.78 (0.75-0.81) vs 0.84 (0.83-0.86); S/D:2.61 (2.33-3.42), 3.01 (2.20-3.93) vs 3.72 (3.06-4.49); P<0.05]. Group C demonstrated lower PI and RI than Group B (P<0.05). IL-2 levels in Groups C and B were higher than in Group A[3.88 (2.71-5.01), 3.59 (2.73-4.38) vs 3.16 (2.11-3.25) ng/L, P<0.05], while IL-4, IL-6, IL-10, and TNF-α levels were significantly lower (IL-4: Z=1.428, 2.421; IL-6: Z=1.754, 2.435; IL-10: Z=1.754, 2.854; TNF-α: Z=1.961, 1.765; P<0.05). Group C had lower IL-6 levels than Group B (Z=3.976, P<0.05). Biochemical pregnancy rate, clinical pregnancy rate, and live birth rate in Group C were significantly higher than in Group A (75% vs 40%, 70% vs 35%, 60% vs 20%, P<0.05). No significant differences in early miscarriage rates were observed among the groups (χ²=3.750, P>0.05). [Conclusion] Intrauterine autologous PRP perfusion in CE patients enhances pregnancy and live birth rates, improves pregnancy outcomes post-FET, and demonstrates superior efficacy in endometrial repair and receptivity with two PRP perfusions compared to a single perfusion. This provides a safe and effective therapeutic option for optimizing outcomes in CE patients with prior implantation failure.

One of the significant hurdles in telemedicine, particularly in ophthalmology, is the absence of direct physical examination. This specialty depends extensively on specialized instruments that typically require proficient operators. Visual function tests are crucial for both outpatient and inpatient ophthalmic services, playing a vital role in screening, diagnosing, monitoring treatment effectiveness, and managing follow-ups for various eye conditions. The progress in mobile technology has paved the way for expanding these tests beyond traditional clinic settings, promoting the creation of patient-focused, straightforward, cost-effective, and efficient measurement tools. In light of the swift advancement of digital technologies, this article reviews the characteristics, and reliability of self-administered visual function tests tools, including visual acuity, refractive error assessment, visual field, contrast sensitivity, and color vision, along with other pertinent diagnostic tools that have been developed and validated for accuracy and repeatability through research, with a view to providing ophthalmologists and patients with scientific and practical references when selecting and using these tools, further promoting efficiency and efficacy of teleophthalmology.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Background/Aims: Obesity is associated with several gastrointestinal (GI) disorders and has been identified as a potential risk factor for various GI symptoms. Bowel frequency is an important indicator of bowel function. However, the causal link between obesity and gastrointestinal motility remains uncertain. This study aims to determine the causal effect of overall and central obesity on stool frequency. Methods: Four obesity-related anthropometric indicators–body mass index, body fat percentage, waist circumference (WC), and waist-tohip ratio (WHR)–were investigated. Individual-level baseline information from the UK Biobank was used to explore observational associations between obesity and stool frequency. Additionally, summary-level data from published genome-wide association studies were subjected to two-sample Mendelian randomization (MR) analyses to examine causal associations. Results: For all 4 indicators of obesity, higher levels of obesity were associated with more frequent bowel movements after adjusting for demographic characteristics, lifestyle, and dietary factors. After rigorous screening, 482 body mass index single nucleotide polymorphisms (SNPs), 7 body fat percentage SNPs, 48 WC SNPs, and 287 WHR SNPs were identified as instrument variables for MR analysis. The MR results were generally consistent with observational findings, proving that the associations observed in the overall obesity indicators were causal. For central obesity, the association between WHR and stool frequency remained consistent in both analysis phases, whereas WC showed a multidirectional association. Conclusions Obesity-related anthropometric indicators were causally associated with increased stool frequency in the overall and central obesity groups. Weight loss could be a potential approach to improve gastrointestinal regularity in individuals with obesity.

Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P＜0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P＞0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P＜0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.

Objective:To evaluate the prevalence, potential risk factors, and correlation between coronary and peripheral microvascular dysfunction in heart failure with non-reduced ejection fraction (nHFrEF) patients.Methods:This was a prospective registry study. nHFrEF patients admitted to Zhongshan Hospital affiliated with Fudan University from December 2021 to December 2023 were enrolled. According to coronary flow reserve (CFR) or reactive congestion index (RHI), enrolled patients were divided into coronary microvascular endothelial dysfunction (CMD) group (CFR<2.5) and no CMD group (CFR≥2.5) or peripheral microvascular endothelial dysfunction (MED) group (RHI<1.67) and no MED group (RHI≥1.67). Patients′ general information, laboratory and auxiliary examination data were collected. Univariate and multivariate logistic regression were used to analyze the influencing factors of CMD and MED in nHFrEF patients, and Spearman correlation analysis was used to evaluate the correlation between MED and CMD.Results:A total of 142 nHFrEF patients were enrolled, aged 69.0 (59.0, 74.0) years, with a male proportion of 66.9% (95/142). The grouping results were as follows: (1) According to CFR, there were 73 cases in the CMD group and 69 cases in the no CMD group; (2) According to RHI, there were 57 cases in the MED group and 85 cases in the no MED group. The prevalence of CMD and MED in this study was 51.4% (73/142) and 40.1% (57/142), respectively. Univariate logistic regression analysis showed that increased heart rate, chronic kidney disease, atrial fibrillation, elevated N-terminal pro-B type natriuretic peptide levels, and increased urinary albumin/creatinine ratio were risk factors for CMD, while increased RHI was a protective factor for CMD; Atrial fibrillation is a risk factor for MED, while increased CFR is a protective factor for MED. Incorporating clinically significant variables from univariate analysis into multivariate analysis, the results showed that increased heart rate and elevated RHI remained risk and protective factors for CMD, respectively; increased CFR remains a protective factor for MED. Spearman correlation analysis showed that CFR was negatively correlated with lg urinary albumin/creatinine ratio, lg cardiac troponin T, lg N-terminal pro-B type natriuretic peptide, and heart rate; RHI is positively correlated with CFR.Conclusions:The prevalence of CMD and MED in nHFrEF patients is high, and the two have a certain positive correlation. Increased heart rate and RHI are risk and protective factors for CMD, respectively, while increased CFR is a protective factor for MED. MED may be a potential therapeutic target for nHFrEF patients.

Objective:To investigate the impact of different target sites, number of treatments, and age on setup errors in dual-isocenter radiotherapy for breast cancer, and to provide a basis for planning target volume (PTV) margin expansion.Methods:A retrospective analysis was conducted on data from 15 patients with left-sided breast cancer who underwent dual-isocenter breath-hold radiotherapy in the Department of Radiotherapy Oncology at the Second Hospital of Hebei Medical University from May 2021 to May 2023. Setup errors were acquired using a Varian TrueBeam STX linear accelerator. Patients were grouped by target site (supraclavicular/chest wall), treatment phase (early/late), and age (younger/older). Non-parametric tests were used to analyze differences in setup errors in : vertical (Vrt), longitudinal (Lng), lateral (Lat) directions, and pitch, roll, and rotation (Rtn) angles. The formula proposed by van Herk was applied to calculate PTV margins.Results:The Vrt direction setup error in the supraclavicular region (0.2 cm) was smaller than that in the chest wall region (0.26 cm), but errors and margin expansions in other directions were larger ( P<0.05 for Lng and Lat directions). No significant correlation was observed in Vrt direction errors between the two sites ( P=0.062), while significant correlations were found in the other directions and angles (all P<0.05). As treatment progressed, setup errors increased in the Vrt and Rtn directions for the supraclavicular region, and in the Vrt, Lng, Lat directions and Rtn angle for the chest wall region. Among these, only the increase in Lat direction error for the chest wall region was statistically significant ( P=0.028). The PTV margins in the late phase group (except for the Lat direction of the supraclavicular region) were greater than or equal to those in the early phase group. Elderly patients had significantly larger setup errors than younger patients in Vrt, Lng, and Lat directions for the supraclavicular region, as well as in Vrt and Lat directions for the chest wall region (all P<0.05). Conclusions:In dual-isocenter radiotherapy for breast cancer, the supraclavicular region requires larger PTV margins than the chest wall region, and elderly patients require greater margins overall. Mid-course rescanning is recommended. If cone-beam CT guidance cannot be ensured for every session, expansion of PTV margins should be considered for the supraclavicular region and elderly patients to reduce the risk of geographic miss.

Objective This study aimed to investigate the correlation of cerebral perfusion and cognitive function status in patients with minor stroke(MS)or transient ischemic attack(TIA)complicated by severe intracranial arterial stenosis or occlusion(hereafter referred to as ICAS-MSTIA).Methods Retrospectively enrol consecutive ICAS-MSTIA patients admitted to the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,from June 2023 to May 2024.In the meantime,healthy controls were openly recruited.The ICAS-MSTIA patients were divided into two groups based on the side of intracranial large artery stenosis or occlusion:the left intracranial large artery involvement group and the right intracranial large artery involvement group.All patients with intracranial large artery stenosis or occlusion underwent MR scanning within 2 weeks after the first episode of TIA or MS,while there was no specific time requirement for MR examination in the healthy control group.On the day of MR scanning,the Montreal cognitive assessment(MoCA)scale was used to evaluate the participants'global cognitive function and performance in various cognitive domains,including visuospatial/executive function,naming,attention,language,abstraction,delayed recall,and orientation.General information of all participants was collected,including age,sex,educational level,body mass index,and history of smoking and alcohol consumption.Clinical data were collected from both left and right intracranial large artery involvement groups,including cerebrovascular risk factors(such as,diabetes mellitus,hypertension,and hyperlipidemia),National Institutes of Health stroke scale(NIHSS)score at admission,responsible stenotic or occluded arteries(internal carotid artery,middle cerebral artery),degree of stenosis in the responsible vessel(severe stenosis[stenosis rate 70%-99%],occlusion[stenosis rate100%])and non-responsible vessel(no stenosis[0],mild stenosis[stenosis rate＞0-49%]),collateral circulation compensation(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASTIN/SIR]collateral circulation classification),and responsible events(TIA,MS).General data and MoCA scale scores were compared across the three groups,while clinical data were compared between the left and right intracranial large artery involvement groups.Statistical parametric mapping 12(SPM 12)was used to perform voxel-wise independent samples t-tests on cerebral blood flow(CBF)differences among the left ICAS-MSTIA group,right ICAS-MSTIA group,and healthy control group,with cluster-level family-wise error(FWE)correction applied for adjustment.Multiple linear regression analysis was conducted to evaluate the relationship between global CBF values and total MoCA scores in ICAS-MSTIA patients with left or right intracranial large artery involvement.Results A total of 33 ICAS-MSTIA patients and 33 healthy controls were enrolled in the study.Among the ICAS-MSTIA patients,21 had left intracranial large artery involvement and 12 had right involvement.(1)Among the three groups,statistically significant differences were observed in the proportions of individuals with reported smoking history(P=0.024)and alcohol consumption history(P=0.011).The left intracranial large artery involvement group had a higher NIHSS score(0[0,2]vs.0[0,0],P=0.044)and a higher proportion of patients with internal carotid artery involvement(13/21 cases vs.2/12 cases,P=0.027)compared with the right side group.No statistically significant differences were observed in other general or clinical data across the three groups or between the two non-control groups(all P＞0.05).(2)Statistically significant differences were found across the three groups in the MoCA scale total score and scores of visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation cognitive domains(all P＜0.05),while no significant difference was noted in the naming score(P=0.063).The left intracranial large artery involvement group had lower total MoCA score and lower scores in visuospatial/executive function,attention,language,abstraction,delayed recall,and orientation in comparison to the healthy control group(all P＜0.016 7).The right intracranial large artery involvement group had significantly lower scores in language,abstraction,and orientation domains than the healthy control group(all P＜0.016 7).Additionally,the left side group had a lower attention domain score than the right side group(P＜0.016 7).No other statistically significant differences were found in pairwise comparisons(all P＞0.016 7).(3)Patients in both the left and right intracranial large artery involvement groups exhibited a significant decrease in CBF in extensive regions on the affected side,including the temporal lobe,dorsolateral prefrontal cortex,and occipital lobe.Furthermore,after correction,in the left involvement group CBF was higher in the contralateral lingual gyrus,cuneus,and calcarine sulcus compared with the healthy control group(P＜0.05).While in the right involvement group,no regions had increased CBF compared to the healthy control group.(4)Multiple linear regression showed positive correlation between CBF in ipsilateral precentral gyrus and superior temporal gyrus,and the total MoCA score in patients with left intracranial large artery involvement(FWE-corrected,P＜0.05).In contrast,there was no correlation between CBF and total MoCA score in patients with right intracranial large artery involvement.Conclusions ICAS-MSTIA patients exhibited various degrees of impairment in cerebral perfusion and cognitive function.A significant positive correlation is observed between these two impairments in patients with left intracranial large artery involvement.