Purpose: This study aimed to evaluate the safety and efficacy of gemcitabine and cisplatin (GP) regimen in combination with immune checkpoint inhibitor sintilimab as neoadjuvant therapy for muscle-invasive bladder cancer (MIBC) patients and the feasibility of the following selective bladder sparing surgery. Materials and Methods: Patients with histopathologically confirmed urothelial carcinoma without distant metastases (T2-4a, N ≤ 1, M0, American Joint Committee of Cancer 8th) and with adequate organ function will be enrolled. The therapeutic regimen was sintilimab 200 mg once on day 8, gemcitabine 1,000 mg/m2 and cisplatin 35 mg/m2 once on days 1 and 8, every 21 days for four cycles. The primary endpoint was pathologic complete response (pCR, pT0N0) rate. The secondary end points were ypT < 2 rate, R0 resection rate, event-free survival, and safety. Results: From May 4, 2020, to May 20, 2023, 55 patients were enrolled. Forty-six patients were evaluated for efficacy. Among the 42 patients who underwent surgery, 16 patients (38.0%) achieved pCR. Thirty-three patients (78.6%) achieved pT < 2. With a median follow-up of 15.7 months, the 1-year event-free survival was 91.3%. Notwithstanding the poor pathological baseline characteristic of a high T3-T4a proportion (39.1%), a promising bladder preservation (including 22 patients transurethral resection of bladder tumor, 5 patients partial cystectomy, and 4 surveillances) rate was achieved (67.4%). The most common grade ≥ 3 treatment-related adverse events was neutropenia (n=15, 27.3%), which was related to chemotherapy. There were no grade 3 immune-related adverse events. Conclusion Neoadjuvant GP plus sintilimab is a promising regimen for MIBC patients, with relatively high pT < 2 rate and triggering the emerging roles for the multi-disciplinary team decision-making for bladder sparing surgery.

Objective To explore the application value of laparoscopic assisted ileostomy closure after prophylactic ileostomy.Methods A retrospective analysis was conducted on 63 cases of middle and low rectal cancer who received ileostomy closure after prophylactic ileostomy in natural orifice specimen extraction surgery(NOSES)from September 2017 to May 2023.Among them,31 cases underwent laparoscopic assisted ileostomy closure(observation group),and 32 cases underwent conventional open ileostomy closure(control group).The operative time,intraoperative blood loss,time to first ambulation,time to first flatus,time to first liquid diet,postoperative pain score,postoperative hospital stay time,and postoperative complications were compared between the two groups.Results All the 63 cases successfully underwent ileostomy closure.The observation group showed significantly better outcomes than the control group in operative time[(63.2±5.7)min vs.(93.5±4.7)min,t=-23.109,P=0.000],intraoperative blood loss[7.0(6.0,8.0)ml vs.22.5(21.0,24.0)ml,Z=-6.853,P=0.000],time to first ambulation[1.0(1.0,1.0)d vs.2.0(2.0,2.0)d,Z=-5.653,P=0.000],time to first flatus[1.0(1.0,2.0)d vs.2.0(2.0,2.0)d,Z=-5.304,P=0.000],time to first liquid diet[2.0(2.0,3.0)d vs.3.0(2.0,3.0)d,Z=-3.000,P=0.003],postoperative pain score[24 h:3.0(3.0,4.0)vs.4.0(3.0,4.0),Z=-4.501,P=0.000;48 h:2.0(2.0,2.0)vs.3.0(2.0,3.0),Z=-3.750,P=0.000;72 h:1.0(1.0,2.0)vs.2.0(2.0,2.0),Z=-2.996,P=0.003],and postoperative hospital stay[(6.8±1.6)dvs.(8.5±1.5)d,t=-4.297,P=0.000].The observation group had a lower postoperative incision infection rate than the control group[3.2％(1/31)vs.34.4％(11/32),x2=9.908,P=0.002],while no significant differences were observed in incision dehiscence,intestinal obstruction,or abdominal hemorrhage(P＞0.05).Conclusions For patients with middle and low rectal cancer who undergoing ileostomy closure after prophylactic ileostomy in NOSES,laparoscopic assisted ileostomy closure is safe and feasible.Compared with open surgery,it reduces incision infection rate,alleviates postoperative pain,shortens hospital stay,and promotes recovery.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To investigate the effects of moxibustion,filiform needle acupuncture,and electroacupuncture on synovial hypoxia and expression of synovial fibrosis markers[transforming growth factor(TGF)-β and collagen alpha-1(Ⅰ)chain(COL1A1)]in knee osteoarthritis(KOA)rats.Methods:Fifty Sprague-Dawley rats were randomly divided into a normal group,a model group,a moxibustion group,an acupuncture group,and an electroacupuncture group,with 10 rats in each group.Except for the normal group,rats in the other four groups were injected with sodium iodoacetate into the right knee joint cavity to establish KOA models.The right Futu(ST32)and Zusanli(ST36)were selected in the moxibustion,acupuncture,and electroacupuncture groups to perform the mild moxibustion with moxa sticks,filiform needle acupuncture,or electroacupuncture,respectively.Each intervention lasted 15 min,once every other day,and continued for 4 weeks,with a total of 14 interventions.The Lequesne score was used to evaluate the degree of knee dysfunction before and after intervention,and the rat's right knee joint diameter was measured to evaluate the degree of knee swelling.Morphological changes of the right knee joint synovial tissue were observed using hematoxylin-eosin staining.Hypoxia probe immunofluorescence staining was used to observe the degree of synovial hypoxia in rats.Western blotting was used to detect the protein expression levels of hypoxia-inducible factor(HIF)-1α,TGF-β,and COL1A1 in the synovial tissue of the right knee joints.Results:Before intervention,the Lequesne score and the right knee joint diameter in the other four groups increased significantly compared to the normal group(P<0.01).After intervention,the Lequesne score and the right knee joint diameter increased significantly in the model group compared to the normal group(P<0.01)together with worsened cartilage deformation and osteophytes,inflammatory cell infiltration and fibrosis in synovial tissue,and hypoxia degree,and the expression levels of HIF-1α,TGF-β,and COL1A1 proteins in the knee joint synovial tissue of rats increased(P<0.01).The Lequesne score and the right knee joint diameter decreased significantly(P<0.01 or P<0.05),the cartilage morphology was normal without obvious osteophytes,and the hypoxia degree reduced in the three intervention groups compared to the model group.Among them,the moxibustion group had the most notable improvement in hypoxia,synovial tissue fibrosis,angiogenesis,and inflammatory cell infiltration.The expression levels of HIF-1α,TGF-β,and COL1A1 proteins decreased in the moxibustion and electroacupuncture groups(P<0.01),and the expression levels of HIF-1α and TGF-β proteins were decreased in the acupuncture group(P<0.01).Conclusion:Moxibustion,filiform needle acupuncture,and electroacupuncture improve knee joint function and reduce knee joint swelling in KOA rats.The mechanism may be to improve synovial fibrosis of the knee joint by regulating HIF-1α;moxibustion has the best effect on improving hypoxia among the three interventions,but the effect of filiform needle acupuncture on COL1A1 is not significant.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption. Methods: Renal tubule-specific Cckbr-knockout (CckbrCKO) mice and wild-type (WT) mice were utilized to investigate the effect of renal CCKBR on SGLT2 and systemic glucose homeostasis under normal diet, high-fat diet (HFD), and HFD with a subsequent injection of a low dose of streptozotocin. The regulation of SGLT2 expression by gastrin/CCKBR and the underlying mechanism was explored using human kidney (HK)-2 cells. Results: CCKBR was downregulated in kidneys of diabetic mice. Compared with WT mice, CckbrCKO mice exhibited a greater susceptibility to obesity and diabetes when subjected to HFD. In vitro experiments using HK-2 cells revealed an upregulation of glucose transporters after incubation with high glucose, a response that was significantly attenuated following gastrin intervention. The glucose uptake from the culture medium of cells was altered accordingly. Moreover, gastrin administration effectively mitigated hyperglycemia in WT diabetic mice by inhibition of SGLT2 mediated glucose reabsorption, but this effect was compromised in the absence of CCKBR, as seen in CckbrCKO mice. Mechanistically, gastrin/CCKBR substantially reduced SGLT2 expression in HK-2 cells exposed to high glucose, via modulating Erkuclear factor-kappa B (NF-κB) pathway. Conclusion Our study underscores the crucial role of renal gastrin/CCKBR in SGLT2 regulation and glucose reabsorption, and renal gastrin/CCKBR can be a promising therapeutic target for diabetes.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory ( Star ) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor ( Ar ) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.
Animals ; Male ; Leydig Cells/metabolism* ; Mice ; Dependovirus/genetics* ; Sertoli Cells/metabolism* ; Gene Silencing ; Genetic Vectors ; Testis/cytology*

OBJECTIVES: To study the clinical characteristics of pediatric Behçet syndrome (BS). METHODS: A retrospective review was conducted on the medical records of children hospitalized in the Department of Pediatrics at the Second Hospital of Hebei Medical University between December 2014 and December 2024 who met diagnostic criteria for BS. RESULTS: Among 45 children with BS, 26 (58%) were male. Oral aphthous ulcers were the most common manifestation (43/45, 96%), followed by genital ulcers (23/45, 51%) and gastrointestinal involvement (18/45, 40%). Genital ulcers were more frequent in girls, whereas ocular involvement was more common in boys (P<0.05). The pathergy test was positive in 10 (22%), and HLA-B51 was positive in 13 (29%). Fecal calprotectin (FC) was elevated in 16 (36%); gastrointestinal involvement was more frequent in children with elevated FC than in those with normal FC (P<0.05). According to the respective criteria, 17 (38%) patients met the International Study Group criteria (1990), 33 (73%) met the International Criteria for Behçet Disease (2014), and 13 (29%) met the Pediatric Behçet Disease criteria (2015). CONCLUSIONS Pediatric BS shows marked clinical heterogeneity. HLA-B51 is associated with disease susceptibility.
Humans ; Behcet Syndrome/genetics* ; Male ; Female ; Child ; Retrospective Studies ; Adolescent ; Child, Preschool ; Leukocyte L1 Antigen Complex/analysis* ; HLA-B51 Antigen

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.
Humans ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Mutation ; Adult ; Repressor Proteins/genetics* ; Adolescent ; Retrospective Studies ; Aged ; Nucleophosmin ; Young Adult ; Transplantation, Homologous ; Prognosis ; Survival Rate