Nomogram for predicting intolerable postoperative early enteral nutrition following definitive surgery for small intestinal fistula: a cohort study.

BACKGROUND: This study was designed to develop and validate a nomogram for predicting intolerable early enteral nutrition (EEN) following definitive surgery (DS) for small intestinal fistula. METHODS: A total of 377 patients, recruited from January 2016 to September 2023, was randomly allocated into development (n=251) and validation (n=126) groups in a 2:1 ratio. Risk factors were identified using the nomogram. Its performance was assessed based on calibration, discrimination, and clinical utility, with validation confirming its effectiveness. RESULTS: Of the 377 patients, 87 (23.1%) were intolerant to EEN, including 59 (23.1%) in the development cohort and 28 (22.1%) in the validation cohort (P=0.84). Four factors were identified as predictive of intolerable EEN: severe abdominal adhesion, deciliter of blood loss during DS, human serum albumin (Alb) input >40 g during and within 48 hours post-DS, and the visceral fat area (VFA)/total abdominal muscle area index (TAMAI) ratio. The model demonstrated excellent discrimination, with a C-index of 0.79 (95% CI, 0.74-0.87, including internal validation) and robust calibration. In the validation cohort, the nomogram showed strong discrimination (C-index=0.77; 95% CI, 0.64-0.87) and solid calibration. Decision curve analysis affirmed the nomogram's clinical utility. CONCLUSION: This research introduces a nomogram that enables the individualized prediction of intolerable EEN following DS for small intestinal fistula, demonstrating a possible clinical utility.

Dissolved oxygen facilitates efficiency of chlorine disinfection for antibiotic resistance.

Controlling the dissemination of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) is a global concern. While commonly used chlorine disinfectants can damage or even kill ARB, dissolved oxygen (DO) may affect the formation of reactive chlorine species. This leads to the hypothesis that DO may play roles in mediating the effectiveness of chlorine disinfection for antibiotic resistance. To this end, this study investigated the impacts of DO on the efficiency of chlorine disinfection for antibiotic resistance. The results revealed that DO could increase the inactivation efficiency of ARB under chloramine and free chlorine exposure at practically relevant concentrations. Reactive species induced by DO, including H2O2, O2-, and OH, inactivated ARB strains by triggering oxidative stress response and cell membrane damage. In addition, the removal efficiency of extracellular ARGs (i.e. tetA and blaTEM) was enhanced with increasing dosage of free chlorine or chloramine under aerobic conditions. DO facilitated the fragmentation of plasmids, contributing to the degradation of extracellular ARGs under exposure to chlorine disinfectants. The findings suggested that DO facilitates disinfection efficiency for antibiotic resistance in water treatment systems.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Study on the Antitumor Mechanism of Tanshinone IIA In Vivo and In Vitro through the Regulation of PERK-ATF4-HSPA5 Pathway-Mediated Ferroptosis.

As a traditional Chinese medicine, Salvia miltiorrhiza Bunge was first recorded in the Shennong Materia Medica Classic and is widely used to treat "the accumulation of symptoms and masses". The main active ingredient of Salvia miltiorrhiza Bunge, Tanshinone IIA (TIIA), has shown anti-inflammatory, antitumor, antifibrosis, antibacterial, and antioxidative activities, etc. In this study, the results showed that TIIA could inhibit the proliferation and migration of HepG2 cells and downregulate glutathione (GSH) and Glutathione Peroxidase 4 (GPX4) levels; besides, TIIA induced the production of Reactive Oxygen Species (ROS), and upregulated the total iron content. Based on network pharmacology analysis, the antitumor effect of TIIA was found to be focused on the endoplasmic reticulum (ER)-mediated ferroptosis signaling pathway, with protein kinase R (PKR)-like ER kinase (PERK)-activating transcription factor 4 (ATF4)-heat shock 70 kDa protein 5 (HSPA5) as the main pathway. Herein, TIIA showed typical ferroptosis characteristics, and a ferroptosis inhibitor (ferrostatin-1) was used to verify the effect. The antitumor effects of TIIA, occurring through the inhibition of the PERK-ATF4-HSPA5 pathway, were further observed in vivo as significantly inhibited tumor growth and the improved pathological morphology of tumor tissue in H22-bearing mice. In summary, the antitumor mechanism of TIIA might be related to the downregulation of the activation of PERK-ATF4-HSPA5 pathway-mediated ferroptosis.

Bioinformatics analysis revealed the potential crosstalk genes and molecular mechanisms between intracranial aneurysms and periodontitis.

OBJECTIVES: The risk of intracranial aneurysms (IAs) development and rupture is significantly higher in patients with periodontitis (PD), suggesting an association between the two. However, the specific mechanisms of association between these two diseases have not been fully investigated. MATERIALS AND METHODS: In this study, we downloaded IAs and PD data from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. The protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA) was performed to identified key modules and key crosstalk genes. In addition, the immune cell landscape was assessed and the correlation of key crosstalk genes with each immune cell was calculated. Finally, transcription factors (TFs) regulating key crosstalk genes were explored. RESULTS: 127 overlapping DEGs were identified and functional enrichment analysis highlighted the important role of immune reflection in the pathogenesis of IAs and PD. We identified ITGAX and COL4A2 as key crosstalk genes. In addition, the expression of multiple immune cells was significantly elevated in PDs and IAs compared to controls, and both key crosstalk genes were significantly negatively associated with Macrophages M2. Finally, GATA2 was identified as a potential key transcription factor (TF), which regulates two key crosstalk gene. CONCLUSIONS: The present study identifies key crosstalk genes and TF in PD and IAs, providing new insights for further study of the co-pathogenesis of PD and IAs from an immune and inflammatory perspective. Also, this is the first study to report the above findings.

The potential crosstalk genes and molecular mechanisms between glioblastoma and periodontitis.

Despite clinical and epidemiological evidence suggestive of a link between glioblastoma (GBM) and periodontitis (PD), the shared mechanisms of gene regulation remain elusive. In this study, we identify differentially expressed genes (DEGs) that overlap between the GEO datasets GSE4290 [GBM] and GSE10334 [PD]. Functional enrichment analysis was conducted, and key modules were identified using protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). The expression levels of CXCR4, LY96, and C3 were found to be significantly elevated in both the test dataset and external validation dataset, making them key crosstalk genes. Additionally, immune cell landscape analysis revealed elevated expression levels of multiple immune cells in GBM and PD compared to controls, with the key crosstalk genes negatively associated with Macrophages M2. FLI1 was identified as a potential key transcription factor (TF) regulating the three key crosstalk genes, with increased expression in the full dataset. These findings contribute to our understanding of the immune and inflammatory aspects of the comorbidity mechanism between GBM and PD.

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic ß-cell Dysfunction.

OBJECTIVE: While the reduction of transient receptor potential channel subfamily M member 5 (TRPM5) has been reported in islet cells from type 2 diabetic (T2D) mouse models, its role in lipotoxicity-induced pancreatic ß-cell dysfunction remains unclear. This study aims to study its role. METHODS: Pancreas slices were prepared from mice subjected to a high-fat-diet (HFD) at different time points, and TRPM5 expression in the pancreatic ß cells was examined using immunofluorescence staining. Glucose-stimulated insulin secretion (GSIS) defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate (Palm). Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm, and the TRPM5 expression was detected using qRT-PCR and Western blotting. Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown. The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5 (Ad-Trpm5). RESULTS: HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets. Palm reduced TRPM5 protein expression in a time- and dose-dependent manner in MIN6 cells. Palm also inhibited TRPM5 expression in primary mouse islets. Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis. Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique to ß cells. CONCLUSION: Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreatic ß cells both in vivo and in vitro and, in turn, drives ß-cell dysfunction.

Process design and techno-economic analysis of activated carbon derived from anthracite coal.

Activated carbon (AC), renowned for its versatile applications in water treatment, air purification, and industrial processes, is a critical component in environmental remediation and resource recovery strategies. This study encompasses the process modeling of AC production using anthracite coal as a precursor, involving multiple activation stages at different operating conditions, coupled with a detailed techno-economic analysis aimed at assessing the operational feasibility and financial viability of the plant. The economic analysis explores the investigation of economic feasibility by performing a detailed cashflow and sensitivity analysis to identify key parameters influencing the plant's economic performance, including raw material and energy prices, operational and process parameters. Capital and operational costs are meticulously evaluated, encompassing raw material acquisition, labor, energy consumption, and equipment investment. Financial metrics like Net Present Value (NPV), Internal Rate of Return (IRR), and payout period (POP) are employed, and the results show that AC selling price, raw material cost and plant capacity are the most influential parameters determining the plant's feasibility. The minimum AC production cost of 1.28 $/kg is obtained, corresponding to coal flow rate of 14,550 kg/h. These findings provide valuable insights for stakeholders, policymakers, and investors seeking to engage in activated carbon production from anthracite.

Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies.

BACKGROUND: Recombinant protein vaccines are vital for broad protection against SARS-CoV-2 variants. This study assessed ReCOV as a booster in two Phase 2 trials. RESEARCH DESIGN AND METHODS: Study-1 involved subjects were randomized (1:1:1) to receive 20 µg ReCOV, 40 µg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 participating individuals were randomized (1:1:1) to receive 20 µg ReCOV (pilot batch, ReCOV HA), 20 µg ReCOV (commercial batch, ReCOV TC), or 30 µg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives was to compare the geometric mean titer (GMT) and seroconversion rate (SCR) of neutralizing antibodies induced by one ReCOV booster dose with those of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. RESULTS: Heterologous ReCOV booster doses were safe and induced comparable immune responses to inactivated vaccines and BNT162b2 against Omicron variants and the prototype. They showed significant advantages in cross-neutralization against multiple SARS-CoV-2 variants, surpassing inactivated vaccines and BNT162b2, with good immune persistence. CONCLUSIONS: Heterologous ReCOV boosting was safe and effective, showing promise in combating COVID-19. The study highlights ReCOV's potential for enhanced protection, supported by strong cross-neutralization and immune persistence. CLINICAL TRIAL REGISTRATION: Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.

Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy.

Background: Better therapeutic drugs are required for treating hypertensive diabetic nephropathy. In our previous study, the Huaju Xiaoji (HJXJ) formula promoted the renal function of patients with diabetes and hypertensive nephropathy. In this study, we investigated the therapeutic effect and regulation mechanism of HJXJ in hypertensive diabetic mice with nephropathy. Methods: We constructed a mouse hypertensive diabetic nephropathy (HDN) model by treating mice with streptozotocin (STZ) and nomega-nitro-L-arginine methyl ester (LNAME). We also constructed a human glomerular mesangial cell (HGMC) model that was induced by high doses of sugar (30 mmol/mL) and TGFß1 (5 ng/mL). Pathological changes were evaluated by hematoxylin and eosin (H&E) staining, periodic acid Schiff (PAS) staining, and Masson staining. The fibrosis-related molecules (TGFß1, fibronectin, laminin, COL I, COL IV, α-SMA, and p-smad2/3) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression of endoplasmic reticulum stress, fibrosis molecules, and their downstream molecules were assessed using qPCR and Western blotting assays. Results: Administering HJXJ promoted the renal function of HDN mice. HJXJ reduced the expression of ER stress makers (CHOP and GRP78) and lncMGC, miR379, miR494, miR495, miR377, CUGBP2, CPEB4, EDEM3, and ATF3 in HDN mice and model HGMCs. The positive control drugs (dapagliflozin and valsartan) also showed similar effects after treatment with HJXJ. Additionally, in model HGMCs, the overexpression of CHOP or lncMGC decreased the effects of HJXJ-M on the level of fibrosis molecules and downstream target molecules. Conclusion: In this study, we showed that the HJXJ formula may regulate ERS-lncMGC/miRNA to enhance renal function in hypertensive diabetic mice with nephropathy. This study may act as a reference for further investigating whether combining HJXJ with other drugs can enhance its therapeutic effect. The findings of this study might provide new insights into the clinical treatment of hypertensive diabetic nephropathy with HJXJ.

Synthesis and antibacterial evaluation of novel psoralen derivatives against methicillin-resistant Staphylococcus aureus (MRSA).

Today, the bacterial infections caused by multidrug-resistant pathogens seriously threaten human health. Thereby, there is an urgent need to discover antibacterial drugs with novel mechanism. Here, novel psoralen derivatives had been designed and synthesized by a scaffold hopping strategy. Among these targeted twenty-five compounds, compound ZM631 showed the best antibacterial activity against methicillin-resistant S. aureus (MRSA) with the low MIC of 1 µg/mL which is 2-fold more active than that of the positive drug gepotidacin. Molecular docking study revealed that compound ZM631 fitted well in the active pockets of bacterial S. aureus DNA gyrase and formed a key hydrogen bond binding with the residue ASP-1083. These findings demonstrated that the psoralen scaffold could serve as an antibacterial lead compound for further drug development against multidrug-resistant bacterial infections.

Modulation of SEMA4D-modified titanium surface on M2 macrophage polarization via activation of Rho/ROCK-mediated lactate release of endothelial cells: In vitro and in vivo.

SEMA4D-modified titanium surfaces can indirectly regulate macrophages through endothelial cells to achieve an anti-inflammatory effect, which is beneficial for healing soft tissues around the gingival abutment. However, the mechanism of surface-induced cellular phenotypic changes in SEMA4D-modified titanium has not yet been elucidated. SEMA4D activates the RhoA signaling pathway in endothelial cells, which coordinates metabolism and cytoskeletal remodeling. This study hypothesized that endothelial cells inoculated on SEMA4D-modified titanium surfaces can direct M2 polarization of macrophages via metabolites. An indirect co-culture model of endothelial cells and macrophages was constructed in vitro, and specific inhibitors were employed. Subsequently, endothelial cell adhesion and migration, metabolic changes, Rho/ROCK1 expression, and inflammatory expression of macrophages were assessed via immunofluorescence microscopy, specific kits, qRT-PCR, and Western blotting. Moreover, an in vivo rat bilateral maxillary implant model was constructed to evaluate the soft tissue healing effect. The in vitro experiments showed that the SEMA4D group had stronger endothelial cell adhesion and migration, increased Rho/ROCK1 expression, and enhanced release of lactate. Additionally, decreased macrophage inflammatory expression was observed. In contrast, the inhibitor group partially suppressed lactate metabolism and motility, whereas increased inflammatory expression. The in vivo analyses indicated that the SEMA4D group had faster and better angiogenic and anti-inflammatory effects, especially in the early stage. In conclusion, via the Rho/ROCK1 signaling pathway, the SEMA4D-modified titanium surface promotes endothelial cell adhesion and migration and lactic acid release, then the paracrine lactic acid promotes the polarization of macrophages to M2, thus obtaining the dual effects of angiogenesis and anti-inflammation.

Exercise, Spinal Microglia and Neuropathic Pain: Potential Molecular Mechanisms.

As one of the most common neuropathic disorders, neuropathic pain often has a negative impact on patients with persistent pain, mood disorders and sleep disturbances. Currently, neuropathic pain is not treated with any specific drug, instead, drugs for other diseases are used as replacements in clinics, but most have adverse effects. In recent years, the role of spinal cord microglia in the pathogenesis of neuropathic pain has been widely recognized, and they are being explored as potential therapeutic targets. Spinal microglia are known to be involved in the pathogenic mechanisms of neuropathic pain through purine signaling, fractalkine signaling, and p38 MAPK signaling. Exercise is a safe and effective treatment, and numerous studies have demonstrated its effectiveness in improving neurological symptoms. Nevertheless, it remains unclear what the exact molecular mechanism is. This review summarized the specific molecular mechanisms of exercise in alleviating neuropathic pain by mediating the activity of spinal microglia and maintaining the phenotypic homeostasis of spinal microglia through purine signaling, fractalkine signaling and p38 MAPK signaling. In addition, it has been proposed that different intensities and types of exercise affect the regulation of the above-mentioned signaling pathways differently, providing a theoretical basis for the improvement of neuropathic pain through exercise.

Comparative efficacy of sequential treatment and open abdomen approaches for corrosive abdominal hemorrhage due to inadequate drainage of duodenal leakage: a cohort study.

BACKGROUND: Intra-abdominal bleeding resulting from inadequate drainage of duodenal leakage (DL) is typically caused by the corrosiveness of duodenal fluid. Open abdomen (OA) treatment addresses both the drainage and bleeding simultaneously. However, a sequential treatment (ST) approach involving hemostasis through transcatheter arterial embolization (TAE) followed by percutaneous drainage of source control has emerged as an alternative method. This study aimed to evaluate the prognosis of ST in cases of DL-induced intra-abdominal bleeding. METHODS: This retrospective cohort study included 151 participants diagnosed with DL-induced intra-abdominal bleeding from January 2004 to December 2010, and January 2013 to December 2021. The ST and OA groups were established based on the treatment method applied. Propensity score-matching (PSM) matched patients in the ST group with those in the OA group. RESULTS: Among the 151 patients, 61 (40.4%) died within 90 days after the bleeding episode. ST was associated with a lower mortality rate (28.2% vs. 51.3% adjusted odds ratio [OR] = 0.34; 95% confidence interval [CI] 0.17-0.68; P = 0.003) compared to OA. Following PSM, ST remained the only factor associated with reduced mortality (OR = 0.32; 95% CI 0.13-0.75; P = 0.009). Moreover, ST demonstrated a higher rate of initial hemostasis success before (90.1% [64/71] vs. 77.5% [62/80]; adjusted OR = 2.84; 95% CI 1.07-7.60; P = 0.04) and after PSM (94.4% [51/54] vs. 77.8% [42/54], adjusted OR = 3.85; 95% CI 2.15-16.82; P = 0.04). Additionally, ST was associated with a lower incidence of rebleeding within 90 days after the initial bleeding, before (7 vs. 23; adjusted OR 0.41; 95% CI 0.18-0.92; P = 0.03) and after PSM (5 vs. 14; adjusted OR 0.37; 95% CI 0.15-0.93; P = 0.03). CONCLUSIONS: Applying ST involving TAE and subsequent percutaneous drainage might be superior to OA in lowering the mortality in DL-induced intra-abdominal hemorrhage.

Safety and Immunogenicity of a Recombinant Two-Component SARS-CoV-2 Protein Vaccine: Randomized, Double-Blind, Placebo-Controlled Phase I and Phase II Studies.

INTRODUCTION: ReCOV is a recombinant protein vaccine that aims to induce cross-neutralization against SARS-CoV-2 variants. The phase I and phase II studies were conducted in New Zealand and the Philippines, respectively, for ReCOV primary series. METHODS: Both studies were randomized, double-blind, placebo-controlled designed among COVID-19 vaccine-naïve healthy adults who received two doses of study vaccination with a 21-day interval. In phase I, 100 younger (15-55 years) and older (56-80 years) subjects were 4:1 randomized to receive ReCOV (20 µg or 40 µg) or placebo. In the phase II study, 347 subjects (≥ 18 years) were 2:1 randomized to receive 40 µg ReCOV or placebo. Subjects that received ReCOV were followed up for 6 months after the second dosing. The safety outcomes included solicited and unsolicited AEs, SAEs, and AESIs. The immunogenicity outcomes were live-virus neutralizing antibody (NAb) against prototype, while pseudovirus NAbs against several SARS-CoV-2 variants were included in phase II as well. RESULTS: No related SAE, AESI, or AE leading to early discontinuation were reported. The AE incidences were higher in ReCOV groups than placebo group in phase I while they were similar between study groups in phase II. The majority of solicited AEs were mild or moderate with median duration of 1.0-4.0 days. The common (≥ 10%) solicited AEs in phase I were injection site reactions, headache, pyrexia, fatigue, and myalgia, and common reported (≥ 5%) ones in phase II included injection site pain, headache, and pyrexia. Robust neutralizing activities against the prototype were observed in ReCOV groups, peaking at 14 days post the second dosing: in phase I, the GMTs for 20 µg and 40 µg ReCOV groups were 1643.2 IU/mL (95% CI 1188.5, 2271.9) and 1289.2 IU/mL (95% CI 868.3, 1914.1) in younger adults, and 1122.3 IU/mL (95% CI 722.6, 1743.1) and 680.3 IU/mL (95% CI 440.2, 1051.4) in older adults, respectively, while in the ReCOV group of phase II, the GMTs for subjects with seronegative and seropositive status at baseline were 3741.0 IU/mL (95% CI 3113.4, 4495.0) and 6138.3 IU/mL (95% CI 5255.1, 7169.9), respectively. In phase II, substantial levels of pseudovirus NAbs against SARS-CoV-2 variants were demonstrated; the peak GMTs for prototype, Omicron BA.2, and BA.4/5 were 8857, 4441, and 2644, and 15,667.3, 7334.3, and 4478.8 among seronegative and seropositive subjects, respectively. The neutralization persisted till 6 months post the second dosing, with only 2.5- to 5.2-fold declines for Omicron variants. CONCLUSIONS: Two doses of 20 µg and 40 µg ReCOV are safe and immunogenic against SARS-CoV-2 prototype. The cross-neutralizing activities against Omicron variants support ReCOV advance to late-stage clinical trials. TRIAL REGISTRATION: Phase I study, clinicaltrials.gov NCT04818801; phase II study, clinicaltrials.gov NCT05084989.

An alternative negative pressure treatment for enteroatmospheric fistula resulting from small intestinal leakage caused by incision dehiscence.

Background: To investigate the efficacy of an alternative negative pressure treatment for the treatment of enteroatmospheric fistula transformed from small intestinal leakage due to incision dehiscence after abdominal surgery. Methods: Patients with an enteroatmospheric fistula from small intestinal leakage owing to incision dehiscence following abdominal surgery between January 2010 and December 2019 were retrospectively reviewed. Results: A total of 83 patients (mean age: 38.3 ± 11.6 years; Body mass index: 19.9 ± 2.2 kg/m2) were enrolled. Of the 83 patients, 59 (71.1 %) achieved fistula closure. High-output fistula (Hazard ratio = 0.48; 95 % Confidence interval: 0.29-0.81; P = 0.006) and abdominal wall thickness >2 cm (Hazard ratio = 2.76; 95 % Confidence interval: 1.35-5.67; P = 0.006) were identified as factors affecting fistula closure. Lastly, 11/83 (13.3 %) patients exhibited re-dehiscence. Conclusion: Appropriately applying the alternative negative pressure treatment may enable fistula closure in patients with enteroatmospheric fistula resulting from small intestinal leakage caused by incision dehiscence.

Versatile Injectable Carboxymethyl Chitosan Hydrogel for Immediate Hemostasis, Robust Tissue Adhesion Barrier, and Antibacterial Applications.

Iatrogenic ulcers resulting from endoscopic submucosal dissection surgery remain a significant clinical concern due to the risk of uncontrolled bleeding. Herein, we have developed an injectable shear-thinning hydrogel cross-linked through electrostatic interactions and hydrogen bonding. The hydrogel underwent comprehensive characterization, focusing on rheological behavior, injectability, microstructure, film-forming capability, adhesion, swelling behavior, degradation kinetics, antibacterial efficacy, hemostatic performance, and biocompatibility. The incorporation of poly(vinyl alcohol) notably enhanced the internal structural stability and injection pressure, while the Laponite content influenced self-healing ability, modulus, and viscosity. Additionally, the hydrogel exhibited pH sensitivity, appropriate degradation, and swelling rates and displayed favorable film-forming and adhesion properties. Notably, it demonstrated excellent resistance against Escherichia coli and Staphylococcus aureus, highlighting its potential to create an optimal wound environment. In vivo studies further confirmed the hydrogel's exceptional hemostatic performance, positioning it as an optimal material for endoscopic submucosal dissection (ESD) surgery. Moreover, cell experiments and hemolysis tests revealed high biocompatibility, supporting their potential to facilitate the healing of iatrogenic ulcers post-ESD surgery. In conclusion, our hydrogels hold great promise as endoscopic treatment materials for ESD-induced ulcers given their outstanding properties.

Drug-target affinity prediction method based on multi-scale information interaction and graph optimization.

Drug-target affinity (DTA) prediction as an emerging and effective method is widely applied to explore the strength of drug-target interactions in drug development research. By predicting these interactions, researchers can assess the potential efficacy and safety of candidate drugs at an early stage, narrowing down the search space for therapeutic targets and accelerating the discovery and development of new drugs. However, existing DTA prediction models mainly use graphical representations of drug molecules, which lack information on interactions between individual substructures, thus affecting prediction accuracy and model interpretability. Therefore, transformer and diffusion on drug graphs in DTA prediction (TDGraphDTA) are introduced to predict drug-target interactions using multi-scale information interaction and graph optimization. An interactive module is integrated into feature extraction of drug and target features at different granularity levels. A diffusion model-based graph optimization module is proposed to improve the representation of molecular graph structures and enhance the interpretability of graph representations while obtaining optimal feature representations. In addition, TDGraphDTA improves the accuracy and reliability of predictions by capturing relationships and contextual information between molecular substructures. The performance of the proposed TDGraphDTA in DTA prediction was verified on three publicly available benchmark datasets (Davis, Metz, and KIBA). Compared with state-of-the-art baseline models, it achieved better results in terms of consistency index, R-squared, etc. Furthermore, compared with some existing methods, the proposed TDGraphDTA is demonstrated to have better structure capturing capabilities by visualizing the feature capturing capabilities of the model using Grad-AAM toxicity labels in the ToxCast dataset. The corresponding source codes are available at https://github.com/Lamouryz/TDGraph.

Effects of Shenling Baizhu powder on intestinal microflora metabolites and liver mitochondrial energy metabolism in nonalcoholic fatty liver mice.

Background & purpose: Non-alcoholic fatty liver disease (NAFLD) is characterised by the excessive accumulation of triglycerides in the liver. Shenling Baizhu powder (SLBZP) is formulated from various natural medicinal plants that protect the liver and are used to treat intestinal diseases. SLBZP improves the symptoms of NAFLD. However, its mechanism of action remains unclear. Herein, we investigated the ameliorative effect of SLBZP on model mice with high-fat-diet (HFD)-induced NAFLD. Additionally, we evaluated the impact of SLBZP on the intestinal flora and its metabolites and mitochondrial energy metabolism in NAFLD. Methods: We used HFD to establish a mouse model of NAFLD. Different drug interventions were administered. We measured serum biochemical indices. Liver sections were visualised with hematoxylin-eosin and oil red O staining. 16S rDNA amplicon sequencing technology was used to analyse the diversity and abundance of the intestinal flora. Short-chain fatty acids (SCFAs) in the intestinal contents were detected using GC-MS. Liver tissue was sampled to detect mitochondrial membrane functional indices. Western blotting was used to determine the levels of mitochondrial pathway-related proteins, namely, uncoupling protein 2 (UCP2), adenosine monophosphate-activated protein kinase (AMPK) and inhibitory factor 1 (IF1) of F1Fo ATP synthesis/hydrolase, in the liver. Results: The spleen-invigorating classic recipe of SLBZP reduced liver lipid deposition in mice with HFD-induced NAFLD. Additionally, SCFAs produced by intestinal flora metabolism regulated the UCP2/AMPK/IF1 signalling pathway involved in liver mitochondrial energy metabolism to improve the liver mitochondrial membrane permeability, respiratory state and oxidative phosphorylation efficiency of mice with NAFLD. Finally, SLBZP increased the liver ATP level. Conclusion: Our results suggest that the therapeutic effect of SLBZP on NAFLD is related to the regulation of hepatic mitochondrial energy metabolism by intestinal flora and its metabolites and is possibly associated with the UCP2/AMPK/IF1 signalling pathway.