ObjectiveHepatocyte nuclear factor 4-alpha (HNF4A) is a critical transcription factor in the liver and pancreas. Dysfunctions of HNF4A lead to maturity onset diabetes of the young 1 (MODY1). Notably, MODY1 patients with HNF4A pathogenic mutations exhibit decreased responses to arginine and reduced plasma triglyceride levels, but the mechanisms remain unclear. This study aims to investigate the potential target genes transcriptionally regulated by HNF4A and explore its role in these metabolic pathways. MethodsA stable 293T cell line expressing the HNF1A reporter was overexpressed with HNF4A. RNA sequencing (RNA-seq) was performed to analyze transcriptional differences. Transcription factor binding site prediction was then conducted to identify HNF4A binding motifs in the promoter regions of relevant target genes. ResultsRNA-seq results revealed a significant upregulation of transmembrane 4 L six family member 5 (TM4SF5) mRNA in HNF4A-overexpressing cells. Transcription factor binding predictions suggested the presence of five potential HNF4A binding motifs in the TM4SF5 promoter. Finally, we confirmed that the DR1 site in the -57 to -48 region of the TM4SF5 promoter is the key binding motif for HNF4A. ConclusionThis study identified TM4SF5 as a target gene of HNF4A and determined the key binding motif involved in its regulation. Given the role of TM4SF5 as an arginine sensor in mTOR signaling activation and triglyceride secretion, which closely aligns with phenotypes observed in MODY1 patients, our findings provide novel insights into the possible mechanisms by which HNF4A regulates triglyceride secretion in the liver and arginine-stimulated insulin secretion in the pancreas.

Objective To evaluate the efficacy of complete pelvic floor peritoneal reconstruction in reducing postoperative ileus incidence and accelerating recovery following laparoscopic radical cystectomy with orthotopic neobladder construction.Methods A retrospective study was conducted to select 62 patients who underwent the operation in Qujing Hospital Affiliated to Kunming Medical University from January 2017 to September 2024.According to whether complete pelvic floor peritoneal reconstruction was performed during the operation,they were divided into the conventional group(n=25)and the reconstruction group(n=37).Postoperative ileus rates and recovery parameters were compared to assess the clinical value of complete pelvic floor peritoneal reconstruction.Results The reconstruction group showed better postoperative recovery compared to the routine group:gastrointestinal function recovery time[3(2,4)d vs 4(3,5)d,P=0.032],abdominal drainage time[12(10,13.5)d vs 14(12,15)d,P=0.006],pelvic drainage time[12(9,13.5)d vs 14(11,16)d,P=0.015],postoperative hospital stay[18(15.5,26)d vs 25(17,30.5)d,P=0.016],and hospital expenses[(53,695.67±10,182.43)yuan vs(60,803.73±14,449.24)yuan,P=0.027].Postoperative nutritional markers,including total protein[(64.49±6.82)g/L vs.(61.56±4.03)g/L,P=0.038]and albumin[(36.08±5.29)g/L vs.(33.40±3.57)g/L,P=0.020],were higher in the reconstruction group.No significant difference was found in ileus incidence(44.00%vs.32.43%,P=0.355).Other parameters—baseline characteristics,postoperative globulin and prealbumin levels,gastric tube retention,stent/catheter removal time,and complications(anastomotic leakage,urinary fistula,wound infection)—showed no intergroup differences(P>0.05).Conclusion The application of complete pelvic floor peritoneal reconstruction technique in laparoscopic radical cystectomy with orthotonic neobladder provides better protection for the intestine,reduces surgical area adhesions,promotes gastrointestinal function recovery,shortens abdominal and pelvic drainage times,accelerates patient rehabilitation,reduces hospital stay and expenses.However,whether it can effectively reduce postoperative intestinal obstruction rates still requires more data and experimental verification.

Objective To investigate the application effect of cold snare endoscopic mucosal resection(CS-EMR)in the treatment of 6 to 9 mm colorectal small polyps.Methods A total of 82 patients with small colonic polyps in our hospital from March 2022 to August 2023 were collected and divided into the observation group(45 cases received CS-EMR)and the control group[37 cases received hot snare endoscopic mucosal resection(HS-EMR)]according to different surgical methods.The clinical efficacy,polyp resection status,complete polyp resection rate,perioperative indicators and occurrence of complications were compared between the two groups.Results Follow-up for 1 month after operation,the effective rate of treatment in the observation group was higher than that in the control group(P<0.05).There was no statistically significant difference in the polyp resection status or perioperative indicators between the two groups(P>0.05).There was no statistically significant difference in the complete polyp resection rates of patients with different pathological types or total complete resection rate between the two groups(P>0.05).The incidence of delayed bleeding and endoscopic hemostasis rate in the observation group were lower than those in the control group(P<0.05).Conclusion The complete resection rate of 6～9 mm colorectal polyps through CS-EMR was comparable to that of HS-EMR,and CS-EMR has a better efficacy and lower risk of perioperative bleeding,along with higher safety.

BACKGROUND:Patients with lumbar disc herniation have different physical deformities due to nucleus pulposus compression and mechanical imbalance. On this basis,Professor Feng Tianyou proposed the "four-step waist type." Professor Feng Wei proposed the objective quantification of three-dimensional scoliosis angle "four-step waist type."OBJECTIVE:To explore the application value of three-dimensional scoliosis angle in evaluating the efficacy of Feng's spinal manipulation in the treatment of patients with lumbar disc herniation.METHODS:A total of 149 hospitalized patients with lumbar disc herniation were enrolled sequentially,including 96 cases of type-Ⅰ/Ⅱ and 55 cases of type-Ⅲ/Ⅳ. The patients were treated with manual therapy for 2 weeks,and 10 healthy volunteers were included as healthy controls. The three-dimensional scoliosis angle was measured using surface topography technology. The difference of three scoliosis angles between patients with type-Ⅰ/Ⅱ and type-Ⅲ/Ⅳ was compared before and after treatment. The difference between patients after treatment and healthy subjects was compered. The difference of three-dimensional scoliosis angles between type-Ⅰ/Ⅱ and type-Ⅲ/Ⅳ after treatment was compared. The intrinsic correlation of each projection plane of three-dimensional scoliosis angle and its correlation with commonly used clinical efficacy scores were explored.RESULTS AND CONCLUSION:(1) The three-dimensional scoliosis angle was significantly different in patients with type-Ⅰ/Ⅱ and type-Ⅲ/Ⅳ before and after treatment (P<0.05). (2) There were significant differences in coronal curve angle and transverse curve angle between patients with type-Ⅰ/Ⅱ,type-Ⅲ/Ⅳ and healthy subjects (P<0.05),but there was no significant difference in sagittal curve angle (P>0.05). (3) There was a correlation between the angles of each section of the three-dimensional angle,and there was a correlation between the three-dimensional angle and the subjective scale. (4) It is indicated that the three-dimensional scoliosis angle can quantitatively evaluate the changes of body deformity before and after treatment. Quantitative indicators can reveal the changes in the patient's condition before and after treatment. The three-dimensional scoliosis angle can reflect the severity of the impact on the patient's living conditions,but the evaluation of scoliosis by a single plane parameter has certain limitations.

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Sini Decoction (SNT) is a traditional formula recognized for its efficacy in warming the spleen and stomach and dispersing cold. However, elucidating the mechanism of action of SNT remains challenging due to its complex multiple components. This study utilized a synergistic approach combining two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE)-based drug affinity responsive target stability (DARTS) with label-free quantitative proteomics techniques to identify the direct and indirect protein targets of SNT in myocardial infarction. The analysis identified 590 proteins, with 30 proteins showing significant upregulation and 51 proteins showing downregulation when comparing the SNT group with the model group. Through the integration of 2D-DIGE DARTS with proteomics data and pharmacological assessments, the findings indicate that protein disulfide-isomerase A3 (PDIA3) may serve as a potential protein target through which SNT provides protective effects on myocardial cells during myocardial infarction.
Myocardial Infarction/genetics* ; Proteomics/methods* ; Drugs, Chinese Herbal/chemistry* ; Animals ; Protein Disulfide-Isomerases/genetics* ; Male ; Two-Dimensional Difference Gel Electrophoresis/methods* ; Humans ; Rats ; Rats, Sprague-Dawley ; Electrophoresis, Gel, Two-Dimensional

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To summarize and analyze the clinicopathological characteristics,imaging manifestations,treatment and prognosis of anaplastic lymphoma kinase(ALK)-positive histiocytosis(APH)involving the central nervous system(CNS),so as to enhance understanding of this rare disease.Methods A retrospective analysis was conducted on 5 cases of CNS-involved APH diagnosed in Huashan Hospital,Fudan University between 2019 and 2023.Clinical,imaging and pathological data were collected,and supplemented by immunohistochemical staining(IHC),fluorescence in situ hybridization(FISH)and high-throughput sequencing for auxiliary diagnosis and molecular characterization.The findings were summarized and integrated with previous literature for a comprehensive analysis.Results All five patients were male,with a mean age of 27.6 years,in which 2 cases exhibited multi-system involvement,while 3 cases exhibited single system involvement.Imaging revealed multiple intracranial lesions in multi-system cases and solitary lesions in single system cases,with well-defined boundaries and homogeneous enhancement.Histologically,tumor cells were intermingled with lymphocytes,displaying an alternating"light and dark"pattern in 1 case.Granuloma-like structures were observed in 4 cases,along with frequent nuclear grooves,indentations and convolutions.Tumor cells usually infiltrated surrounding tissues.IHC demonstrated that tumors expressed histiocytic markers(CD68/CD163)and ALK predominantly expressed in the cytoplasm.FISH confirmed ALK gene rearrangements in all patients,while high-throughput sequencing identified KIF5B-ALK fusions in 2 cases.All single system CNS cases achieved complete remission after surgical resection with or without adjuvant chemotherapy/ALK inhibitors.Among multi-system cases,one achieved partial remission,and one experienced relapse and progression.Conclusion CNS APH is prone to preoperative misdiagnosis.Its histopathological features,ALK immunohistochemical expression,and ALK gene fusions are critical for diagnosis.Patients with single system involvement demonstrate overall superior outcomes compared to multi-system cases.Total resection is effective for localized disease,while multi-system cases require systemic therapy.Multidisciplinary collaboration is crucial for precise diagnosis and treatment.