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 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:To explore the clinical values of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carbohydrate antigen 724 (CA724) and gastrin 17 (G-17) detections in the early diagnosis of gastric cancer patients.Methods:A retrospective case-control study was conducted. A total of 120 patients with gastric diseases who were admitted to General Hospital of Xuzhou Mining Group from January 2019 to December 2021 were selected. According to the pathological results of gastroscopy examination, the patients were divided into gastric ulcer group (23 cases), atrophic gastritis group (58 cases) and early gastric cancer group (39 cases). The healthy control group consisted of 30 healthy individuals who underwent physical examination during the same period. All participants were detected for serum levels of CEA, CA125, CA199, CA724, and G-17. The levels of various indicators in each group were compared. Using the pathological results of gastroscopy as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the efficacy of various indicators in distinguishing early gastric cancer from healthy individuals, gastric ulcer and atrophic gastritis.Results:The serum levels of CA125 [ M ( Q1, Q3)] [19.94 (8.29, 22.99) U/ml vs. 6.03 (4.07, 10.48) U/ml, 7.49 (4.96, 12.19) U/ml, 7.54 (6.20, 11.91) U/ml], CA199 [32.09 (15.68, 41.97) U/ml vs. 19.19 (10.01, 30.05) U/ml, 21.00(16.01, 32.71) U/ml, 18.95 (13.90, 32.76) U/ml], CA724 [19.55 (3.91, 26.25) U/ml vs. 4.61 (3.06, 5.24) U/ml, 4.09 (3.37, 5.00) U/ml, 4.88 (3.92, 5.46) U/ml] and G-17 [21.01 (14.67, 24.00) pmol/L vs. 11.80 (10.07, 16.58) pmol/L, 12.74 (11.09, 14.69) pmol/L, 12.08 (8.40, 15.10) pmol/L] in the early gastric cancer group were higher than those in the gastric ulcer group, atrophic gastritis group and healthy control group, and the differences were statistically significant (all P < 0.05). The CEA level in the early gastric cancer group, gastric ulcer group and atrophic gastritis group was all higher than that in the healthy control group [4.38 (3.22, 7.56) ng/ml, 4.51 (3.37, 5.51) ng/ml, 4.49 (4.13, 5.09) ng/ml vs. 3.95 (2.16, 4.44) ng/ml], and the differences were statistically significant (all P < 0.05). ROC curve analysis showed that among all indicators, the area under the curve (AUC) of G-17 for distinguishing early gastric cancer from healthy individuals was the largest [0.825 (95% CI: 0.728-0.922)], the optimal critical value was 18.21 pmol/L, and the specificity was the highest (96.7%); the AUC of CA125 and CA724 was also relatively high, with values of 0.768 (95% CI: 0.653-0.884) and 0.744 (95% CI: 0.622-0.866), respectively, and the optimal critical values were 15.41 and 39.60 U/ml, respectively, with the corresponding sensitivities of 71.8%, which was the highest among several indicators. Among all indicators, CA125 had the largest AUC for distinguishing early gastric cancer from gastric ulcer, which was 0.829 (95% CI: 0.729-0.930), with an optimal critical value of 11.60 U/ml, and the corresponding sensitivity was also the highest (74.4%); the AUC of CEA and CA724 was 0.534 (0.391-0.677) and 0.786 (0.668-0.903), respectively; the optimal critical values were 7.20 ng/ml and 6.34 U/ml, respectively; the corresponding specificity was 100.0%. Among the various indicators, the AUC of G-17 for distinguishing early gastric cancer from atrophic gastritis was the largest [0.813 (95% CI: 0.710-0.915)]. The specificity of each indicator at the optimal critical value was relatively high (≥ 94.8%), among which the optimal critical values of CEA and CA125 were 7.170 ng/ml and 15.55 U/ml, respectively, with the corresponding specificity of 100.0%; the AUC of CA724 was 0.783 (95% CI: 0.671-0.895), the optimal critical value was 6.40 U/ml, and the corresponding sensitivity was 71.8%, which was the highest among the several indicators. Conclusions:CEA, CA125, CA199, CA724, and G-17 have high sensitivity and detection rate in the differential diagnosis of early gastric cancer, gastric ulcer and atrophic gastritis, and have certain clinical values in the diagnosis of early gastric cancer and potential for clinical auxiliary diagnosis.

Objective To investigate the neurovascular coupling(NVC)status in the acute phase of patients with minor ischemic stroke(MIS)or transient ischemic attack(TIA)due to intracranial large artery moderate-to-severe stenosis or occlusion using multimodal MRI techniques and to explore its correlation with quality of life(QoL).Methods This prospective,consecutive study enrolled patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion form the Department of Neurology,the First Affiliated Hospital of Xi'an Jiaotong University,between June 2022 and October 2023.Recruit healthy subjects with matched age,sex,and handedness form the community during the same period.Patients were divided into left-sided involvement and right-sided involvement groups based on the affected side of the responsible vessel,while the healthy subjects were set as the healthy control group.Post-hoc power analysis was performed using G*Power 3.1 software.General characteristics(age,gender,body mass index,education level)were collected and compared across all three groups.Clinical data and QoL assessment were collected and compared between the two patient groups.Collected clinical data including type of cerebrovascular events(TIA,MIS),the National Institutes of Health stroke scale(NIHSS)score at admission,the responsible vessel(internal carotid artery,middle cerebral artery)and its side location,the degree of responsibility artery stenosis(moderate-severe stenosis[50%-99%stenosis rate],occlusion[100%stenosis rate]),the intracranial collateral circulation status(American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology[ASITN/SIR]collateral circulation grading),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia,smoking history),and the laboratory test indicators at admission(glycated hemoglobin,triglycerides,total cholesterol,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol,blood uric acid,blood homocysteine).QoL was assessed using the stroke impact scale(SIS),covering eight functional domains and a patient-reported overall recovery item.Multimodal MR data were acquired for all subjects.Whole-brain cerebral blood flow(CBF)images were generated using statistics parameter mapping 12(SPM 12)software,while regional homogeneity(ReHo)images were generated using DPABI software.The voxel-wise ratio of CBF to ReHo(CBF/ReHo)was calculated as the regional NVC parameter.Differences in regional NVC characteristics were compared between patient groups and the healthy control group.Correlations between NVC parameters and SIS scores within patient groups were explored.Results(1)A total of 38 patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion were included(26 males,12 females,aged 36-69 years,with mean age of[52±11]years),with 23 in the left-sided involvement group and 15 in the right-sided involvement group.Nineteen healthy subjects were included(10 males,9 females,aged 37-67 years,with mean age of[53±10]years).Post-hoc power analysis showed statistical power of 0.808 for comparing the left-sided involvement group with the healthy control group and 0.762 for comparing the right-sided involvement group with control group.(2)No statistically significant differences were found on gender,age,education level,or body mass index across the three groups(all P＞0.05).No statistically significant differences were observed on the type of cerebrovascular event,cerebrovascular risk factors,distribution of the responsible vessel,degree of stenosis in the responsible vessel,admission NIHSS score,or laboratory test results between the two patient groups(all P＞0.05).There were no statistically significant differences in the total SIS score and the scores of subscales between the two patient groups(all P＞0.05).(3)Compared with the healthy control group,the left-sided involvement group exhibited reduced CBF/ReHo values in the left superior and middle temporal gyri,supramarginal gyrus,middle and inferior frontal gyri,precentral gyrus,angular gyrus,postcentral gyrus,insula,and posterior cerebellar lobe(FDR-corrected,all P＜0.05).In the right-sided involvement group,reduced CBF/ReHo values were observed in the right supramarginal gyrus,right postcentral gyrus,inferior temporal gyrus,and insula(FDR-corrected,all P＜0.05).(4)Correlation analysis revealed that the SIS total score in the left-sided involvement group negatively correlated with CBF/ReHo values in the right inferior frontal gyrus(T=-5.91)and the right middle temporal gyrus(T=-6.65,FDR-corrected,both P＜0.05).The SIS subscale score for activities of daily living in the left-sided involvement group showed negative correlations with CBF/ReHo values in the right angular gyrus(T=-7.36),right medial superior frontal gyrus(T=-6.97),right orbitofrontal cortex(T=-8.99),and left thalamus(T=-7.51,FDR-corrected,all P＜0.05).No significant correlation was observed between the SIS total score and CBF/ReHo values in patients with right-sided involvement group.The SIS subscale for communication score in the right-sided involvement group correlated with CBF/ReHo in the left lingual gyrus(T=-12.15),left olfactory cortex(T=-7.68),and right anterior cingulate and paracingulate cortex(T=-9.46,FDR-corrected,all P＜0.05).Conclusions Patients with MIS or TIA due to intracranial large artery moderate-to-severe stenosis or occlusion show abnormal NVC in the acute phase,especially those with left hemisphere involvement,who exhibit more extensive impairments.QoL in left-sided involvement patients is strongly linked to NVC in the right orbitofrontal cortex and right middle temporal gyrus.These findings require further validation in larger-scale studies.

Objective:To explore the clinical values of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), carbohydrate antigen 724 (CA724) and gastrin 17 (G-17) detections in the early diagnosis of gastric cancer patients.Methods:A retrospective case-control study was conducted. A total of 120 patients with gastric diseases who were admitted to General Hospital of Xuzhou Mining Group from January 2019 to December 2021 were selected. According to the pathological results of gastroscopy examination, the patients were divided into gastric ulcer group (23 cases), atrophic gastritis group (58 cases) and early gastric cancer group (39 cases). The healthy control group consisted of 30 healthy individuals who underwent physical examination during the same period. All participants were detected for serum levels of CEA, CA125, CA199, CA724, and G-17. The levels of various indicators in each group were compared. Using the pathological results of gastroscopy as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the efficacy of various indicators in distinguishing early gastric cancer from healthy individuals, gastric ulcer and atrophic gastritis.Results:The serum levels of CA125 [ M ( Q1, Q3)] [19.94 (8.29, 22.99) U/ml vs. 6.03 (4.07, 10.48) U/ml, 7.49 (4.96, 12.19) U/ml, 7.54 (6.20, 11.91) U/ml], CA199 [32.09 (15.68, 41.97) U/ml vs. 19.19 (10.01, 30.05) U/ml, 21.00(16.01, 32.71) U/ml, 18.95 (13.90, 32.76) U/ml], CA724 [19.55 (3.91, 26.25) U/ml vs. 4.61 (3.06, 5.24) U/ml, 4.09 (3.37, 5.00) U/ml, 4.88 (3.92, 5.46) U/ml] and G-17 [21.01 (14.67, 24.00) pmol/L vs. 11.80 (10.07, 16.58) pmol/L, 12.74 (11.09, 14.69) pmol/L, 12.08 (8.40, 15.10) pmol/L] in the early gastric cancer group were higher than those in the gastric ulcer group, atrophic gastritis group and healthy control group, and the differences were statistically significant (all P < 0.05). The CEA level in the early gastric cancer group, gastric ulcer group and atrophic gastritis group was all higher than that in the healthy control group [4.38 (3.22, 7.56) ng/ml, 4.51 (3.37, 5.51) ng/ml, 4.49 (4.13, 5.09) ng/ml vs. 3.95 (2.16, 4.44) ng/ml], and the differences were statistically significant (all P < 0.05). ROC curve analysis showed that among all indicators, the area under the curve (AUC) of G-17 for distinguishing early gastric cancer from healthy individuals was the largest [0.825 (95% CI: 0.728-0.922)], the optimal critical value was 18.21 pmol/L, and the specificity was the highest (96.7%); the AUC of CA125 and CA724 was also relatively high, with values of 0.768 (95% CI: 0.653-0.884) and 0.744 (95% CI: 0.622-0.866), respectively, and the optimal critical values were 15.41 and 39.60 U/ml, respectively, with the corresponding sensitivities of 71.8%, which was the highest among several indicators. Among all indicators, CA125 had the largest AUC for distinguishing early gastric cancer from gastric ulcer, which was 0.829 (95% CI: 0.729-0.930), with an optimal critical value of 11.60 U/ml, and the corresponding sensitivity was also the highest (74.4%); the AUC of CEA and CA724 was 0.534 (0.391-0.677) and 0.786 (0.668-0.903), respectively; the optimal critical values were 7.20 ng/ml and 6.34 U/ml, respectively; the corresponding specificity was 100.0%. Among the various indicators, the AUC of G-17 for distinguishing early gastric cancer from atrophic gastritis was the largest [0.813 (95% CI: 0.710-0.915)]. The specificity of each indicator at the optimal critical value was relatively high (≥ 94.8%), among which the optimal critical values of CEA and CA125 were 7.170 ng/ml and 15.55 U/ml, respectively, with the corresponding specificity of 100.0%; the AUC of CA724 was 0.783 (95% CI: 0.671-0.895), the optimal critical value was 6.40 U/ml, and the corresponding sensitivity was 71.8%, which was the highest among the several indicators. Conclusions:CEA, CA125, CA199, CA724, and G-17 have high sensitivity and detection rate in the differential diagnosis of early gastric cancer, gastric ulcer and atrophic gastritis, and have certain clinical values in the diagnosis of early gastric cancer and potential for clinical auxiliary diagnosis.

Objective:To analyze the differences in the clinical characteristics of patients with adenomyosis of different magnetic resonance imaging (MRI) types and the differences in treatment effects after the application of dienogest.Methods:A total of 176 patients with adenomyosis who were admitted to Peking University Third Hospital from June 2017 to February 2023 were included in the study, and all of them were clearly classified by pelvic MRI and treated with dienogest. The clinical characteristics and treatment of the patients were retrospectively collected, and the patients were divided into endogenous type, exogenous type and penetrating type by MRI. The differences in clinical symptoms, imaging features and treatment effect of patients with adenomyosis of different MRI types were analyzed.Results:(1) The percentages of patients with endogenous, exogenous, and penetrating types were 40.9% (72/176), 35.2% (62/176) and 23.9% (42/176), respectively. The proportion of dysmenorrhea in patients with endogenous type (90.3%, 65/72) was significantly lower than those of exogenous type (100.0%, 62/62) and penetrating type (97.6%, 41/42; χ2=7.853, P=0.020), while there was no significant difference between exogenous type and penetrating type ( P>0.05). There were no statistically significant differences in menarche time, menstrual cycle and menstrual period among the three types of patients (all P>0.05), there was also no statistically significant difference in the proportion of menstrual abnormalities (including heavy and irregular menstrual bleeding; P>0.05). The proportions of ovarian endometrioma and deep infiltrating endometriosis in exogenous and penetrating types were significantly higher than that in endogenous type (all P<0.05). (2) The pain scores of all patients were significantly lower than those before treatment (all P<0.001), the proportion of patients with exogenous type (62.9%, 39/62) who had complete remission after treatment was higher than those of endogenous type (49.2%, 32/65) and penetrating type (46.3%, 19/41), but there was no significant difference in pain relief (i.e. the variation in the pain scores) between the three types ( P>0.05). (3) Endogenous type ( OR=0.361, 95% CI: 0.147-0.883; P=0.026), failure to apply gonadotropin-releasing hormone agonist (GnRH-a) in advance ( OR=0.208, 95% CI: 0.083-0.518; P<0.001), cystic changes ( OR=2.671, 95% CI: 1.108-6.437; P=0.029) and abnormal menstruation ( OR=3.466, 95% CI: 1.464-8.209; P=0.005) were independent risk factors for irregular bleeding after dienogest treatment. Conclusions:(1) There are obvious differences in the clinical characteristics of patients with adenomyosis of different MRI types, and patients with exogenous and penetrating types are more likely to have dysmenorrhea symptoms. (2) Dienogest could significantly alleviate the symptoms of dysmenorrhea in patients with adenomyosis. (3) Endogenous type, failure to take GnRH-a in advance and associated menstrual abnormalities are independent risk factors for irregular bleeding after dienogest treatment.

BACKGROUND: Epidemiological data on chronic diarrhea in the Chinese population are lacking, and the association between obesity and chronic diarrhea in East Asian populations remains inconclusive. This study aimed to investigate the prevalence of chronic diarrhea and its association with obesity in a representative community-dwelling Chinese population. METHODS: This cross-sectional study was based on a multistage, randomized cluster sampling involving 3503 residents aged 20-69 years from representative urban and rural communities in Beijing. Chronic diarrhea was assessed using the Bristol Stool Form Scale (BSFS), and obesity was determined based on body mass index (BMI). Logistic regression analysis and restricted cubic splines were used to evaluate the relationship between obesity and chronic diarrhea. RESULTS: The standardized prevalence of chronic diarrhea in the study population was 12.88%. The average BMI was 24.67 kg/m 2 . Of all the participants, 35.17% (1232/3503) of participants were classified as overweight and 16.13% (565/3503) as obese. After adjustment for potential confounders, individuals with obesity had an increased risk of chronic diarrhea as compared to normal weight individuals (odds ratio = 1.58, 95% confidence interval: 1.20-2.06). A nonlinear association between BMI and the risk of chronic diarrhea was observed in community residents of males and the overall participant group ( P  = 0.026 and 0.017, respectively). CONCLUSIONS This study presents initial findings on the prevalence of chronic diarrhea among residents of Chinese communities while offering substantiated evidence regarding the significant association between obesity and chronic diarrhea. These findings offer a novel perspective on gastrointestinal health management.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Young Adult ; Body Mass Index ; China/epidemiology* ; Chronic Disease/epidemiology* ; Cross-Sectional Studies ; Diarrhea/epidemiology* ; Obesity/complications* ; Prevalence ; East Asian People/statistics & numerical data*

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.

[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.