Chagas disease(American trypanosomiasis)is a zoonosis caused by Trypanosoma cruzi,which severely affects public health.Recently,with changes in economic globalization and increased population mobility,this disease has gradually spread from the original Latin American epidemic areas to non-epidemic areas,such as Europe,thus showing a trend of globalization.The main trans-mission routes have changed from transmission via the Triatomine vector to blood transfusion transmission,mother-to-child transmis-sion,oral transmission,and other routes.Consequently,Chagas disease is spreading globally,and more people are increasingly vul-nerable to infection.This article retrospectively reviews research on the transmission routes of Chagas disease,analyzes the changing trends in transmission routes,and provides a scientific basis for the formulation and optimization of Chagas disease prevention and con-trol strategies from a One Health perspective.

Objective To investigate the prognosis of patients with negative sentinel lymph nodes(SLN)after neoadjuvant chemotherapy(NAC)for breast cancer who are exempt from axillary lymph node dissection(ALND)and evaluate its safety in clinical treatment.Methods Clinical data of 2,163 patients initially diagnosed with breast cancer and having negative SLNs after NAC were se-lected from the SEER database from 2018 to 2021.Among them,373 patients underwent only SLN biopsy(SLNB group),and 1,790 patients underwent ALND(ALND group).Propensity score matching(PSM)was used to control for confounding factors,and the Kaplan-Meier method was em-ployed to analyze the overall survival rate.Univariate and multivariate Cox regression analyses were conducted to identify prognostic factors influencing the exemption from ALND in patients with negative SLNs after NAC for breast cancer.Results Before PSM,significant differences were observed be-tween the two groups in terms of clinical tumor stage,molecular subtype,estrogen receptor(ER)sta-tus,progesterone receptor(PR)status,human epidermal growth factor receptor 2(HER-2)status,efficacy of NAC,and breast surgery method(P＜0.05).After PSM,363 patients were included in each group.Univariate Cox regression analysis after PSM revealed that age,clinical tumor stage,and ER status were associated with overall survival(OS)of patients(P＜0.05).There was no sig-nificant difference in OS between patients who underwent SLNB and those who underwent ALND(P＞0.05).Multivariate Cox regression analysis indicated that age and clinical tumor stage were independent factors influencing OS in patients with negative SLNs after NAC.Survival curve analysis after PSM showed no statistically significant difference in overall survival rate between the SLNB and ALND groups(P=0.278).Conclusion Exemption from ALND in patients with negative SLNs af-ter NAC is feasible and does not affect the overall survival rate of patients.

ObjectiveThe nucleolar protein PES1 (Pescadillo homolog 1) plays critical roles in ribosome biogenesis and cell cycle regulation, yet its involvement in cellular senescence remains poorly understood. This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role. MethodsInitially, we assessed PES1 expression patterns in two distinct senescence models: replicative senescent mouse embryonic fibroblasts (MEFs) and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells. Subsequently, PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types. Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays, respectively. The expression of senescence-associated proteins (p53, p21, and Rb) and SASP factors (IL-6, IL-1β, and IL-8) were analyzed by Western blot or qPCR. Furthermore, Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology. ResultsPES1 expression was significantly downregulated in senescent MEFs and HepG2 cells. PES1 knockdown resulted in decreased EdU-positive cells and increased SA‑β‑gal-positive cells, indicating proliferation inhibition and senescence induction. Mechanistically, PES1 suppression activated the p53-p21 pathway without affecting Rb expression, while upregulating IL-6, IL-1β, and IL-8 production. Notably, PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress, as evidenced by aberrant nucleolar morphology. ConclusionOur findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent (but Rb-independent) cellular senescence, highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Urinary incontinence is a common complication following robot-assisted radical prostatectomy (RARP). Urethral length has been identified as a factor affecting postoperative continence recovery. In this meta-analysis, we examined the association between use of the maximal urethral length preservation (MULP) technique and postoperative urinary continence in patients undergoing RARP. We conducted a comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library up to December 31, 2023. The quality of the literature was assessed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed to synthesize data and calculate the odds ratio (OR) from eligible studies on continence and MULP. Six studies involving 1869 patients met the eligibility criteria. MULP was positively associated with both early continence (1 month after RARP; Z = 3.62, P = 0.003, OR = 3.10, 95% confidence interval [CI]: 1.68-5.73) and late continence (12 months after RARP; Z = 2.34, P = 0.019, OR = 2.10, 95% CI: 1.13-3.90). Oncological outcomes indicated that MULP did not increase the overall positive surgical margin rate or the positive surgical margin status at the prostate apex (both P > 0.05). In conclusion, the use of the MULP technique in RARP significantly improved both early and late postoperative continence outcomes without compromising oncological outcomes.
Humans ; Prostatectomy/adverse effects* ; Robotic Surgical Procedures/methods* ; Male ; Urethra/surgery* ; Urinary Incontinence/prevention & control* ; Postoperative Complications/etiology* ; Prostatic Neoplasms/surgery* ; Organ Sparing Treatments/methods*

OBJECTIVE: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. METHODS: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. RESULTS: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the "estrogen signaling pathway" identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. CONCLUSION The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8-SULT1E1 groups than in the rAAV8-empty groups.

Chagas disease(American trypanosomiasis)is a zoonosis caused by Trypanosoma cruzi,which severely affects public health.Recently,with changes in economic globalization and increased population mobility,this disease has gradually spread from the original Latin American epidemic areas to non-epidemic areas,such as Europe,thus showing a trend of globalization.The main trans-mission routes have changed from transmission via the Triatomine vector to blood transfusion transmission,mother-to-child transmis-sion,oral transmission,and other routes.Consequently,Chagas disease is spreading globally,and more people are increasingly vul-nerable to infection.This article retrospectively reviews research on the transmission routes of Chagas disease,analyzes the changing trends in transmission routes,and provides a scientific basis for the formulation and optimization of Chagas disease prevention and con-trol strategies from a One Health perspective.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To investigate the value of digital medical 3D technology versus traditional 2D technology in the diagnosis and treatment of solid abdominal tumors in children. Methods:A total of 80 children with solid abdominal tumors who received surgical treatment guided by digital medical 3D technology at Guigang People's Hospital from January 2018 to January 2022 were included in the observation group. An additional 80 children with solid abdominal tumors who received surgical treatment guided by traditional 2D technology at the same hospital from January 2014 to December 2017 were included in the control group. Clinical efficacy was compared between the two groups.Results:The surgical time, intraoperative blood loss, postoperative exhaust time, postoperative hospital stay in the observation group were (111.8 ± 28.9) minutes, (26.8 ± 25.2) mL, (2.2 ± 1.2) days, (7.5 ± 1.4) days, respectively, which were significantly shorter or less than those in the control group [(193.1 ± 66.0) minutes, (86.2 ± 47.0) mL, (3.7 ± 0.9) days, (12.2 ± 3.5) days, t = 7.00, 6.88, 5.87, 7.53, all P < 0.05]. The complete surgical resection rate in the observation group was significantly higher than that in the control group [92.5% (74/80) vs. 81.3% (65/80), χ2 = 4.44, P < 0.05]. The incidence of complications in the observation group was significantly lower than that in the control group [6.3% (5/80) vs. 16.3% (13/80), χ2 = 4.00, P < 0.05]. Conclusion:The utilization of digital medical 3D technology in the surgical treatment of solid abdominal tumors in children can markedly decrease surgical time, reduce intraoperative blood loss, promote postoperative recovery, achieve a high surgical resection rate, and minimize postoperative complications.

Objective To investigate the clinical efficacy of percutaneous closure of foramen ovale guided by transthoracic echocardio-graphy with simply delivery sheath.Methods The clinical data of patients with patent foramen ovale underwent interventional closure and percutaneous closure guided by transthoracic echocardiography with simply delivery sheath in our hospital from January 2020 to December 2022 were analyzed retrospectively,the patients were divided into interventional closure group(40 cases)and simply delivery sheath group(39 cases).The operation time,incidence of surgical complications,and surgical success rates of patients in the two groups were compared.The closure effect were evaluated by ultrasound immediately after surgery.All the patients were followed up for 6 months after surgery to evaluate remission of the symptoms.Results The surgical success rate of simply delivery sheath group(100%)was higher than that of interventional closure group(90.0%),with statistically significant difference(P<0.05).The operation time of simply delivery sheath group was longer than that of interventional closure group,with statistically significant difference(P<0.05).One patient in the interventional closure group had small amount of pericardial effusion during the operation.Two patients had decreased blood pressure and slowed heart rate in simply delivery sheath group,and symptoms disappeared after treatment.There was no significant difference in the incidence of complications between the two groups(P>0.05).After 6-month follow-up,all occluders were in good position and no residual leakage was found.The symptoms of headache or dizziness disappeared in 28 patients in interventional closure group,significantly relieved in 8 patients;the symptoms of headache or dizziness disappeared in 30 patients in simply delivery sheath group,and significantly relieved in 9 patients.Conclusion Percutaneous closure for patent foramen ovale under the guidence of transthoracic echocardiography with simply delivery sheath is safe and feasible with satisfactory efficacy and higher successful rate without radiation hazard.It is worthy of clinical promotion.