Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

Objective To investigate the relationship between the levels of serum suppressor of cytokine signaling 3(SOCS3),growth differentiation factor-15(GDF-15)and liver fibrosis in patients with type 2 dia-betes mellitus(T2DM)combined with non-alcoholic fatty liver disease(NAFLD).Methods A total of 320 patients with T2DM combined with NAFLD who were hospitalized in this hospital from May 2023 to May 2024 were selected as the study group,and another 320 patients with simple T2DM admitted during the same period were selected as the control group.The levels of serum SOCS3 and GDF-15 were determined by en-zyme-linked immunosorbent assay(ELISA).Pearson correlation analysis was used to analyze the correlation between SOCS3,GDF-15 levels and liver fibrosis indicators.Logistic regression analysis was used to analyze the factors affecting the degree of liver fibrosis.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients.Results Compared with the control group,the levels of serum SOCS3,GDF-15,5,type Ⅲ procollagen peptide,laminin and type Ⅳ col-lagen in the study group were significantly increased(P＜0.05).There were statistically significant differ-ences in the levels of type Ⅲ procollagen peptide,laminin and type Ⅳ collagen between the mild to moderate group and the severe group(P＜0.05).Compared with the mild to moderate group,the levels of serum SOCS3 and GDF-15 in the severe group were significantly increased(P＜0.05).The results of Pearson corre-lation analysis showed that serum SOCS3 and GDF-15 in patients with T2DM combined with NAFLD were positively correlated with type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen(P＜0.05).Serum SOCS3,GDF-1 5,type Ⅲ procollagen peptide,laminin and type Ⅳ collagen are risk factors affecting the degree of liver fibrosis in patients with T2DM combined with NAFLD(P＜0.05).The results of the ROC curve showed that the combined diagnosis of serum SOCS3 and GDF-15 for the degree of liver fibrosis in patients with T2DM complicated with NAFLD had the highest area under the curve(AUC),which was superior to the individual diagnosis of each(both P＜0.05),with a corresponding sensitivity of 69.08％and a specificity of 85.71％.The combined diagnosis of the degree of liver fibrosis in patients with T2DM complicated with NAFLD by serum SOCS3,GDF-15,type Ⅲ procollagen peptide,laminin,and type Ⅳ collagen had the highest AUC,which was superior to the individual diagnosis of each index(all P＜0.001),with a corresponding sensi-tivity of 89.47％and a specificity of 97.02％.Conclusion The levels of serum SOCS3 and GDF-15 are elevated in patients with T2DM combined with NAFLD,.The combined diagnosis of serum SOCS3,GDF-15,type Ⅲ procolla-gen peptide,laminin,and type Ⅳ collagen has a high value in the degree of liver fibrosis in patients.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

Objective:Hepatic fibrosis is a common pathological basis for many chronic liver diseases and can progress to cirrhosis,a leading cause of mortality in liver diseases.Early identification and reversal of hepatic fibrosis are key in the treatment of chronic liver disease.This study aims to compare the expression levels of serum core fucosylated low molecular weight kininogen(LMWK-Fc)and alpha-galactosylated(α-Gal)antibodies in patients with hepatic fibrosis at different stages,and to evaluate their diagnostic efficacy for hepatic fibrosis. Methods:A retrospective analysis was conducted on 275 patients with chronic liver disease who visited the Department of Infectious Diseases at the Second Xiangya Hospital of Central South University between June 2022 and March 2023.Among these,115 patients underwent liver biopsy.Based on the extent of collagen deposition and its impact on liver structure and microcirculation,patients were staged from 0 to 4:S0(no significant collagen deposition in liver tissues;liver structure and microcirculation are normal),S1(mild collagen deposition in liver tissues,with partial disruption of lobule structure,but microcirculation remains largely normal),S2(moderate collagen deposition in liver tissues,with partial disruption of lobule structure and microcirculation),S3(extensive collagen deposition in liver tissues,with substantial disruption of lobule structure and microcirculation),and S4(development of cirrhosis,with heavy collagen deposition,complete disruption of lobule structure,and severe impairment of microcirculation).Patients were grouped as no fibrosis(S0),fibrosis(S1-S2),and significant fibrosis(S3-S4).For the 160 patients without liver biopsy,they were categorized based on liver stiffness measurement(LSM)value:no fibrosis(F0:LSM＜7.3 kPa),fibrosis(F1-F2:LSM 7.3-12.4 kPa),and significant fibrosis(F3-F4:LSM＞12.4 kPa).Demographic data(age,gender)and laboratory indicators(alanine transaminase,aspartate transaminase,gamma-glutamyl transferase,alkaline phosphatase,alpha-fetoprotein,platelet count)were collected to calculate the fibrosis-4 index(FIB-4)and aspartate aminotransferase-to-platelet ratio index(APRI).Serum LMWK-Fc and α-Gal antibodies were measured and compared across the groups,and their correlation with fibrosis severity was analyzed.The receiver operating characteristic(ROC)curve was used to assess the predictive value of serum LMWK-Fc and α-Gal antibody levels for hepatic fibrosis. Results:Among the 160 patients without complete liver biopsy,serum α-Gal antibody and LMWK-Fc levels increased progressively from the no fibrosis group to the significant fibrosis group,with statistically significant differences(P＜0.05).Among the 115 patients with liver biopsy,serum LMWK-Fc levels were significantly higher in the fibrosis group and the significant fibrosis groups compared with the no fibrosis group,and α-Gal antibody levels were significantly higher in the significant fibrosis group compared with the no fibrosis group and the fibrosis group(P＜0.001,P=0.032,respectively).Univariate and multivariate linear regression analyses showed that hepatic fibrosis was correlated with gender and LMWK-Fc levels(both P＜0.05),but not with age,α-Gal antibody levels,FIB-4,or APRI(all P＞0.05). Conclusion:The expression levels of serum LMWK-Fc and α-Gal antibodies vary across different stages of hepatic fibrosis,suggesting a potential association with fibrosis progression.LMWK-Fc levels have a certain predictive value for the diagnosis of hepatic fibrosis.

Objective To explore the effect of virtual reality(VR)technology on relieving intraoperative pain in patients receiving transcatheter hepatic artery chemoembolization(TACE).Methods A total of 76 patients,who received TACE from June 2023 to January 2024,were enrolled in this study.Using random number table method,the patients were divided into control group(n=38)and study group(n=38).Intraoperative routine nursing was carried out for the patients of the control group,while on the basis of routine nursing additional VR technology was adopted to relieve the intraoperative pain for the patients of the study group.The degree of intraoperative pain,anxiety symptoms,incidence of intraoperative adverse reactions and patient satisfaction with nursing were compared between the two groups.Results The degree of intraoperative pain in the study group was lower than that in the control group,but the difference between the two groups was not statistically significant(P＞0.05).The analgesic effect of VR was much obvious in patients aged≤55 years and in patients with vascular invasion of liver cancer(P＜0.05).The anxiety score in the study group was lower than that in the control group,the patient satisfaction score in the study group was higher than that in the control group,and the differences between the two groups were statistically significant(both P＜0.05).No statistically significant difference in the incidence of adverse reactions existed between the two groups(P＞0.05).Conclusion Immersive VR technology can effectively reduce the degree of intraoperative pain in patients receiving TACE,especially in patients aged ≤55 years.Besides,VR technology can also reduce the anxiety degree of patients,and improve the degree of intraoperative patient satisfaction with nursing.

OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.

Objective:To evaluate the safety and feasibility of robot assisted total gastrectomy plus hand-sewn esophagojejunostomy.Methods:The clinical data of 72 patients diagnosed with gastric cancer and undergoing total gastrectomy at the First Affiliated Hospital of Ningbo University from Nov 2021 to May 2024 were retrospectively analyzed. They were divided into two groups: robot-assisted total gastrectomy (RATG) group, consisting of 30 patients, and laparoscopic assisted total gastrectomy (LATG) group, consisting of 42 patients . In the RATG group, the digestive tract was reconstructed by manual suture under the robot scope and Roux-Y reconstruction was performed . In LATG group, digestive tract reconstruction was performed using an in vitro stapler and Roux-Y. The clinicopathological data, perioperative indexes, and postoperative follow-up data of both groups were observed and analyzed.Results:All 72 patients successfully completed the operation without conversion to open laparotomy. The total operation time in RATG group was longer than that in LATG group [(235.2±25.8) min vs. (200.7±40.6) min, t=4.099, P<0.05)].RATG was superior to LATG group in terms of digestive tract reconstruction time, postoperative fluid intake time and hospitalization days,the difference was statistically significant [(36.9±3.0) min vs.(39.4±4.5) min, (4.2±0.5) d vs. (5.2±0.6) d、(9.5±1.6) d vs. (10.8±2.4)d, t=-2.554,-7.135,-2.595, all P<0.05]; In terms of postoperative pathology, the number of lymph node dissection in RATG group was higher than that in LATG group [(29.8±6.2) vs. (26.3±7.5), t=2.197, P<0.05]. Conclusion:The application of delayed disconnection hand-sewn esophagojejunostomy in Da Vinci robot total gastrectomy is safe and feasible for cure-intent total gastrectomy in patients of gastric carcinoma.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective:To compare the clinical value of stent assisted intestinal bypass and temporary loop ileostomy in laparoscopic low anterior resection of rectal cancer.Method:In this retrospective analysis, 57 patients undergoing laparoscopic low anterior resection for rectal cancer in the First Affiliated Hospital of Ningbo University from Jan 2020 to Jan 2022 were divided into intestinal bypass group (36 cases) and loop ileostomy group (21 cases).Result:There were no significant differences in postoperative GI function recovery and postoperative complication rate between the two groups (all P>0.05). The levels of albumin, prealbumin and hemoglobin in the intestinal bypass group were better than those in the ileostomy group when evaluated on 3rd months after operation [(40.5±2.3) g/L vs. (38.1±2.6)g/L、(26.4±2.7)mg/dl vs. (24.5±2.0)mg/dl、(137.6±5.9) g/L vs. (134.0±7.0) g/L, t=3.605、2.743、2.085, all P<0.05]. Hospital expenses of the intestinal bypass group was lower [(571 000±7 500) yuan vs. (69 300±9 100) yuan, t=-5.477, P<0.05]. Conclusion:Compared with traditional ileostomy, the stent assisted intestinal bypass reduces trauma with lower expenses and improves patients' status after laparoscopic low anterior resection for rectal cancer.