Background Diarrhea disease is a common intestinal infectious disease, and its incidence is affected by meteorological conditions. A better understanding of its epidemiological patterns and influencing factors, together with the construction of reliable prediction models, is of great significance for precise public health prevention and control. Objective To clarify the epidemic characteristics of adult diarrhea disease in Shanghai, analyze the associations of meteorological factors and a web search index with adult diarrhea disease, and develop and compare forecasting models to support precise regional prevention and control. Methods Weekly surveillance data of adult diarrhea disease cases from the Shanghai Comprehensive Surveillance Information System for Diarrhea Diseases, together with concurrent meteorological observation data and web search index (Baidu index) data from 2014 to 2019, were collected. A distributed lag non-linear model (DLNM) was adopted to analyze the associations of multiple meteorological factors and the web search index with the number of diarrhea disease cases. By integrating meteorological factors and web search index data, three types of forecasting models were developed, including autoregressive integrated moving average (ARIMA), Random Forest, and extreme gradient boosting (Xgboost), and their predictive performances were evaluated. Results Adult diarrhea disease in Shanghai exhibited seasonal variation, with an major incidence peak in summer and winter peaks in some years. The number of cases declined annually after 2015. Mean temperature was significantly associated with the risk of diarrhea disease, and both low and high temperature exposures were associated with increased risks. The highest risk was observed at 32.8°C (RR=2.04, 95%CI: 1.62, 2.55), while the strongest effect of low temperature was observed at 0.9 °C (RR=1.53, 95%CI: 1.25, 1.88). When relative humidity exceeded 69%, the risk of diarrhea disease increased with relative humidity, reaching a peak at 81% (RR=1.20, 95%CI: 1.07, 1.35). When weekly cumulative precipitation exceeded 16 mm, the risk also increased with increasing precipitation, reaching a maximum at 105 mm (RR=1.23, 95%CI: 1.07, 1.42). The web search index was positively associated with the risk of diarrhea disease. Model prediction indicated that both the Random Forest model and the Xgboost model adequately captured the overall trend in diarrhea disease cases, with R² values generally exceeding 0.7. Notably, the Xgboost model demonstrated greater accuracy in capturing peak intensities. Conclusion Meteorological factors are associated with adult diarrhea disease in Shanghai. The web search index may serve as an auxiliary indicator for diarrhea forecasting. Machine learning models, with advantages in integrating multisource data, may provide effective predictive tools for the prevention and control of diarrhea disease.

Multi-arm robotic-assisted uniportal pulmonary resection is an emerging minimally invasive technique that enables anatomical pulmonary resection through a single incision using a multi-arm robotic platform. This consensus was initiated by Shanghai Pulmonary Hospital and developed through a multidisciplinary national expert panel. Using evidence-based methodology and expert survey, it provides a comprehensive overview of the clinical application of this technique, including its definition, indications and contraindications, technical considerations, and learning curve. As the first expert consensus focused on multi-arm robotic-assisted uniportal pulmonary resection, this consensus highlights the feasibility and developmental potential of the technique, which integrates existing robotic systems with uniportal minimally invasive principles. The consensus also offers theoretical and practical guidance for the standardized and safe implementation of the technique.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective To explore the mechanism of Tongluo Baoshen Decoction in improving podocyte injury in rats with IgA nephropathy based on Gprc5b/NF-κB/NLRP3 pathway.Methods Totally 130 SPF-grade male SD rats were randomly divided into a normal group(n=20)and a modeling group(n=110).The IgA nephropathy model was established using a compound modeling method,and 100 modeling rats were randomly divided into model group,losartan potassium group(5 mg/kg),and Tongluo Baoshen Decoction low-,medium-,and high-dosage groups(5.3,10.6,21.2 g/kg),with 20 rats in each group.The administration group was given the corresponding dosage of medication by gavage,while the normal group and model group were given an equal amount of distilled water by gavage once a day.After 4 and 8 weeks of administration,urine samples were collected for 24 hours,and blood and kidney tissue specimens were collected.24-hour urinary protein quantification(24 h-UTP),urinary Nephrin,serum creatinine(SCr),blood urea nitrogen(BUN)and blood uric acid(BUA)contents were detected;RT-qPCR and Western blot were used to detect the expressions of G protein coupled receptor C-family 5b(Gprc5b),nuclear factor(NF)-κB p50,NOD like receptor protein 3(NLRP3),Caspase-1,interleukin(IL)-1β,Nephrin mRNA and protein in renal tissue,respectively;HE,PAS,PASM,Masson staining were used to observe the morphology of renal tissue,immunofluorescence was used to observe IgA deposition in the mesangial area of renal tissue,and transmission electron microscopy was used to observe the ultrastructure of podocytes.Results Compared with the normal group,the model group rats showed significantly increased contents of 24 h-UTP,urinary Nephrin and BUA(P<0.01),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue were significantly increased(P<0.01),while the mRNA and protein expressions of Nephrin were significantly decreased(P<0.01),with mild to moderate proliferation of mesangial cells in the glomerulus,increased mesangial matrix,and immunofluorescence showed clustered and linear deposition of IgA in the mesangial area,electron microscopy showed partial fusion of the foot processes.Compared with the model group,the 24 h-UTP and urinary Nephrin contents in different dosage groups of Tongluo Baoshen Decoction and the losartan potassium group after 4 and 8 weeks administration significantly decreased(P<0.01),with a decrease in BUA content in Tongluo Baoshen Decoction high-dosage group(P<0.05),the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue of Tongluo Baoshen Decoction groups and losartan potassium group decreased(P<0.05,P<0.01),while the mRNA and protein expressions of Nephrin increased(P<0.05,P<0.01),with the proliferation of mesangial cells,the increase of mesangial matrix,the deposition of IgA in the mesangial area,and the fusion of foot processes in renal tissue were alleviated to varying degrees in different dosage groups of Tongluo Baoshen Decoction,with the most significant improvement observed in the high-dosage group.Compared with the 4-week administration,Tongluo Baoshen Decoction high-dose group showed further reductions in 24 h-UTP and urinary Nephrin contents after 8 weeks of administration(P<0.01),further decreases in the mRNA and protein expressions of Gprc5b,NF-κB p50,NLRP3,Caspase-1 and IL-1β in renal tissue(P<0.05,P<0.01),and further increases in the mRNA and protein expressions of Nephrin(P<0.01).Conclusion Tongluo Baoshen Decoction can reduce proteinuria,alleviate renal tissue lesions and improve podocyte injury in IgA nephropathy rats,and its mechanism may be related to the inhibition of Gprc5b/NF-κB/NLRP3 pathway in renal tissue.

Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Objective To study its effect and mechanism of epigallocatechin-3-gallate(EGCG)on the generation of Aβ42 in N2a/APP695swe cells.Methods The N2a/APP695swe cells were cultured in vitro and treated with different concentrations of EGCG(or in combination with LXRβ antagonist GSK2033).The DM-SO group and wild type N2a/wt group were set.The cellular survival rate was detected by the MTT assay;ELISA was used to detect the Aβ42 level;Western blot was used to detect the expression levels of LXRβ,RXRα,ABCA1,caveolin-1 and BACE1 proteins.Results The cellular survival rate and Aβ42 level in the 20,40 μmol/L EGCG cells groups were significantly improved compared with the other groups(P＜0.05),more-over which showed the concentration dependence(P＜0.05).After 20 μmol/L EGCG action,the expression levels of LXRβ,RXRα and ABCA1 protein were increased,the expression levels of caveolin-1 and BACE1 pro-tein were significantly decreased,and the differences were statistically significant(P＜0.05);after treating the cells by combining with GSK2033,the expression levels of LXRβ,RXRα and ABCA1 protein were significantly decreased and caveolin-1 and BACE1 protein expression levels were significantly increased(P＜0.05).Conclu-sion The generation of Aβ42 in N2a/APP695swe cells could be inhibited by EGCG,thus which inhibits the cellular proliferation,and its mechanism may be related to EGCG activating the LXRβ-RXRα-ABCA1 path-way,and then inhibiting the expression of caveolin-1 and BACE1.

Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.