As the intricate interplay between microbiota and the host garners increasing research attention, a significant parallel surge has emerged in the investigation of intestinal bacterial extracellular vesicles (BEVs). Most intestinal bacteria secrete BEVs, which harbor specific cargo molecules and exhibit diverse functions, encompassing interactions among bacteria themselves and between bacteria and the host. These interactions can either bolster host health or contribute to various pathologies. By integrating the characteristics of BEVs, we summarized the current research landscape, delving into the intricate interplay between BEVs and different diseases. Furthermore, we offer a succinct overview of the challenges faced in BEVs-based research, encompassing separation, detection, engineering for drug purposes, clinical diagnostics, safety, and future study. In essence, these summaries may serve as invaluable guides for BEVs as communication tools between the gut microbiome and host, ultimately propelling the discovery of novel studies and drug discovery.

Liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist approved for diabetes and obesity, has shown significant potential in treating metabolic dysfunction-associated steatotic liver disease (MASLD). However, its systematic molecular regulation and mechanisms remain underexplored. In this study, a mouse model of MASLD was developed using a high-fat diet (HFD), followed by Lira administration. Proteomics and glycoproteomics were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS), while potential molecular target analysis was conducted via quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Our results revealed that Lira treatment significantly reduced liver weight and serum markers, including alanine aminotransferase (ALT) and others, with glycosylation changes playing a more significant role than overall protein expression. The glycoproteome identified 255 independent glycosylation sites, emphasizing the impact of Lira on amino acid, carbohydrate metabolism, and ferroptosis. Simultaneously, proteomic analysis highlighted its effects on lipid metabolism and fibrosis pathways. 21 signature molecules, including 7 proteins and 14 N-glycosylation sites (N-glycosites), were identified as potential targets. A Lira hydrogel formulation (Lira@fibrin (Fib) Gel) was developed to extend drug dosing intervals, offering enhanced therapeutic efficacy in managing chronic metabolic diseases. Our study demonstrated the importance of glycosylation regulation in the therapeutic effects of Lira on MASLD, identifying potential molecular targets and advancing its clinical application for MASLD treatment.

Alopecia areata （AA） is a common hair loss disorder， and the core pathogenesis is the internal gene-ration of turbid toxin caused by qi movement disorder in the liver， spleen， and kidney. Turbid toxin serves as both a pivotal etiological trigger and a pathological driver of disease exacerbation. Clinically， AA can be classified into four principal patterns， including liver constraint with spleen deficiency， internal accumulation of damp-heat， liver-kidney depletion， and qi-blood depletion. Therapeutic strategies prioritize clearing and resolving turbid toxin while regulating the qi movement of the liver， spleen， and kidney. Accordingly， different formulas were applied. Self-formulated Shugan Jianpi Huazhuo Formula （疏肝健脾化浊方） is suggested to drain dampness， resolve turbidity， and unblock qi movement. Self-formulated Sanjiao Fenxiao Jiedu Formula （三焦分消解毒方） can be used to clear heat， drain dampness and resolve toxin. Self-formulated Zishen Yanggan Toudu Decoction （滋肾养肝透毒汤） can clear and vent latent toxins， while Self-formulated Guiqi Shengfa Didu Formula （归芪生发涤毒方） is employed to tonify qi and blood， purge toxins， and regenerate vitality. By differentiating and treating AA based on the functional patterns of the liver， spleen， and kidney， this approach expands the application scope of the turbid toxin theory and provides valuable insights for treatment of AA.

The development of novel point-to-point drugs targeting resistance mechanisms is a critical and popular research field; nevertheless, success remains challenging. Therefore, given the short survival time and heightened expectations of patients with advanced NSCLC, the design of various combination therapy strategies––integrating preclinical, clinical, and real-world evidence (such as radiotherapy, chemotherapy, targeted therapy, antibody–drug conjugates, oncolytic viruses, and cell therapy)––may be a wise and practical choice to address the disease. Resistance to immunotherapy involves almost all cell types in the body, primarily cancer cells and T cells involved in immune surveillance. As a result of space limitations, this article focuses on the progress and challenges of various combined strategies for directly eliminating cancer cells. We also emphasize the realignment of treatment goals, shifting from primarily focusing on eliminating cancer cells (via chemotherapy and radiotherapy) to fully utilizing immune regulation to overcome resistance to immune checkpoint inhibitors.

Objective:To analyze the influencing factors of patient loyalty in internet diagnosis and treatment, for references for improving the service quality and promoting the sustainable development of internet diagnosis and treatment.Methods:In November 2023, a simple random sampling method was used to select patients who had received internet diagnosis and treatment as the survey objects and conduct a questionnaire survey on performance expectations, effort expectations, social influence, promotion conditions, price values, patient trust and patient loyalty. By establishing an unified theory of acceptance and use of technology model of influencing factors of patient loyalty in internet diagnosis and treatment, the hypotheses were put forward. The structural equation model (SEM) test and mediation effect test were used to verify the hypothesis path and variable mediation effect, and explore the influencing factors of internet patient loyalty.Results:A total of 1 800 patients were included in this study, including 1 188 patients(66.0%) who received internet diagnosis and treatment≥3 times/month. According to the SEA test, performance expectations ( β=0.296, P<0.001), social influence ( β=0.146, P=0.014), promotion conditions ( β=0.366, P<0.001), price values ( β=0.452, P=0.017), and patient trust ( β=0.459, P<0.001) had a direct positive impact on patient loyalty; Social influence ( β=0.147, P<0.001) and promotion conditions ( β=0.084, P<0.001) had a direct positive impact on patient trust. According to the mediation effect test, patient trust partially mediated the relationship between social influence and patient loyalty ( β=0.071, P=0.018), as well as the relationship between promoting conditions and patient loyalty ( β=0.748, P=0.041). Conclusions:Performance expectations, social influence, promotion conditions, price values, and patient trust had a positive impact on patient loyalty, among which social influence and promotion conditions could enhance patient loyalty by strengthening patient trust. It was suggested that relevant institutions should focus on the service quality of internet diagnosis and treatment, further improve performance expectations, expand social impact, improve promotion conditions and regulate price values, so as to enhance the patient loyalty, promote the wide application and rapid development of internet diagnosis and treatment.

Objective:To investigate the application effect of 3D printed fetal heart model based on ultrasound data combined with case-based learning (CBL) in prenatal ultrasound teaching of complex heart malformations in standardized residency training of ultrasound medicine.Methods:A total of 60 students majoring in ultrasound imaging who received standardized residency training in Ultrasonography Center of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, from September 2020 to August 2022 were enrolled as subjects and divided into experimental group and control group, with 30 students in each group. The students in the experimental group received teaching with 3D printed fetal heart model and CBL teaching, and those in the control group received teaching with hand-painted heart diagram and CBL teaching. The two groups were compared in terms of the score of theoretical examination, the degree of satisfaction with teaching, and the self-rated score of the understanding of each disease before and after teaching, and the correlation of the increase in score with case complexity was also analyzed. MedCalc software was used to perform the t-test and the linear regression analysis. Results:The experimental group had a significantly higher score of theoretical examination than the control group [(85.70±8.70) vs. (71.40±9.50)]. The questionnaire survey showed that the experimental group had better feedbacks than the control group in the aspects such as the degree of satisfaction with teaching ( P<0.05). After the implementation of this teaching model, compared with the control group, the experimental group had significantly higher self-rated scores of the understanding of case 2, case 3, case 4, and case 5 ( P<0.05). The increase in score after teaching was positively correlated with the complexity score of abnormal cases ( R2=0.90, P=0.010; R2=0.94, P=0.010), and the experimental group tended to have a greater regression coefficient. Conclusions:The reasonable application of 3D printed fetal heart model combined with CBL teaching in fetal heart teaching in standardized residency training of ultrasound medicine can help the students to understand and enhance the knowledge of cardiac anatomy, improve the learning experience of fetal echocardiography, and deepen the understanding and awareness of complex congenital heart disease.

Unplanned readmission is one of the adverse outcomes of patients after left ventricular assist device implantation,which seriously affects the prognosis of patients.This article reviews the incidence,causes,influencing factors and intervention measures of unplanned readmission of patients after left ventricular assist device implantation,in order to improve the attention of nursing staff,early identify high-risk groups of unplanned readmission of patients after left ventricular assist device implantation and provide references for formulating personalized intervention measures.

Objective To investigate the predictive value of serum lipoprotein-associated phospho-lipase A2(Lp-PLA2)for long-term prognosis of elderly patients with stable coronary heart dis-ease(CHD).Methods A retrospective trial was conducted on 198 patients with stable CHD ad-mitted to our hospital from January 2016 to December 2018.All of them were followed up for 5 years,and divided into adverse cardiovascular event group(n=42)and control group(n=156)according to whether adverse cardiovascular events occurred during follow-up.Clinical features and Lp-PLA2 level were compared between the two groups.The predictive value of Lp-PLA2 for adverse cardiovascular events was analyzed in elderly patients with stable CHD within 5 years.Re-sults The adverse cardiovascular event group had significantly older age(74.95±7.02 vs 70.17±6.30 years,P=0.000),larger proportions of diabetes(54.76％vs 27.56％,P=0.001),of coronary artery stenosis ≥75％(69.05％vs 47.44％,P=0.013)and of left ventricular ejection fraction(LVEF)＜50％(50.00％vs 28.21％,P=0.008),and higher Lp-PLA2 level(478.38±187.54 U/L vs 308.17±126.73 U/L,P=0.000)when compared with the control group.The AUC value of age and Lp-PLA2 was 0.683(95％CI:0.590--0.776,P＜0.001)and 0.763(95％CI:0.677--0.848,P=0.763),respectively,in predicting the long-term prognosis in elderly patients with stable CHD.Multivariate logistic regression analysis showed that age,diabetes,coronary artery stenosis ≥75％,LVEF＜50％and Lp-PLA2 were independent influencing factors for adverse cardiovascular events within 5 years in elderly patients with stable CHD(P＜0.05,P＜0.01).Con-clusion Increased Lp-PLA2 level is associated with adverse cardiovascular events within 5 years in patients with stable CHD.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

ObjectiveTo investigate the therapeutic effect and mechanism of coptisine on chronic atrophic gastritis （CAG） in rats based on the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodA CAG rat model was induced by multiple factors， including sodium salicylate， N-methyl-N′-nitro-N-nitrosoguanidine （MNNG）， and irregular feeding. The successfully modeled rats were randomly divided into the model group， folic acid group， and high- and low-dose coptisine groups. The high- and low-dose coptisine groups were given coptisine （50， 10 mg·kg^-1， respectively）， and the folic acid group was given folic acid at 2 mg·kg^-1 for 60 days. The pathological changes were detected by hematoxylin-eosin （HE） staining. The ultrastructure of gastric mucosal cells was observed by electron microscopy. Serum pepsinogen Ⅰ （PGⅠ）， pepsinogen Ⅱ （PGⅡ）， and PGⅠ/PGⅡ ratio （PGR） were detected by immunoturbidimetry. Serum gastrin-17 （G-17） level was detected by radioimmunoassay. The content of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in serum of rats was detected by enzyme-linked immunosorbent assay （ELSIA）. Western blot analysis was used to detect the expression levels of TGF-β₁， PI3K， phosphorylated-Akt （p-Akt）， mTOR， and phosphatase and tensin homolog deleted on chromosome 10 （PTEN） in gastric mucosa. The mRNA levels of TGF-β₁， PI3K， Akt， mTOR， PTEN， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and Beclin-1 were detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed atrophy and reduced number of intrinsic glands in the gastric mucosal tissues， as well as inflammatory cell infiltration. The ultrastructure of gastric mucosal cells in the model group displayed nuclear condensation， reduced and swollen mitochondria， and abnormal structure. The serum levels of G-17， PGⅠ， PGR， and the protein and mRNA levels of PTEN in gastric tissues were significantly lower in the model group （P<0.01）， while serum levels of IL-6， IL-1β， TNF-α， and the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR in gastric tissues were significantly higher （P<0.01）. Compared with the model group， various drug intervention groups showed different degrees of improvement in pathological damage and gastric mucosal cell ultrastructure， significantly increased serum levels of G-17， PGⅠ， and PGR （P<0.05，P<0.01）， and significantly decreased levels of IL-6， IL-1β， and TNF-α （P<0.05，P<0.01）. The high-dose coptisine group significantly downregulated the protein and mRNA levels of TGF-β₁， PI3K， Akt， and mTOR （P<0.05，P<0.01）. ConclusionBerberine has a therapeutic effect on CAG in rats， possibly exerting a protective effect on gastric mucosa by inhibiting inflammation and blocking the PI3K/Akt/mTOR signaling pathway.