To analyze the distribution of serotypes and antimicrobial resistance of clinical Salmonella isolates from multiple centers across China.

Although enteric glial cell (EGC) abnormal activation is reported to be involved in the pathogenesis of Parkinson's disease (PD), and inhibition of EGC gliosis alleviated gut and dopaminergic neuronal dysfunction was verified in our previous study, the potential role of gut microbiota on EGC function in PD still need to be addressed. In the present study, fecal microbiota transplantation revealed that EGC function was regulated by gut microbiota. By employing 16S rRNA and metabolomic analysis, we identified that 3-indolepropionic acid (IPA) was the most affected differential microbial metabolite that regulated EGC gliosis. The protective effects of IPA on PD were validated in rotenone-stimulated EGCs and rotenone (30 mg/kg i.g. for 4 weeks)-induced PD mice, as indicated by decreased inflammation, improved intestinal and brain barrier as well as dopaminergic neuronal function. Mechanistic study showed that IPA targeted pregnane X receptor (PXR) in EGCs, and inhibition of IL-13Rα1 involved cytokine-cytokine receptor interaction pathway, leading to inactivation of downstream JAK1-STAT6 pathway. Our data not only provided evidence that EGC gliosis was critical in spreading intestinal damage to brain, but also highlighted the potential role of microbial metabolite IPA in alleviating PD pathological damages through gut-brain axis.

[This corrects the article DOI: 10.1016/j.apsb.2025.02.029.].

Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

Objective To investigate the relationship between serum mannan binding lectin(MBL),histi-dine rich glycoprotein(HRG),interleukin(IL)-23/IL-17 inflammatory axis and cerebral vasospasm(CVS)and prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH)after interventional emboliza-tion.Methods A total of 195 patients with aSAH who underwent interventional embolization treatment in the hospital from March 2019 to February 2022 were selected and were divided into no CVS group(126 cases),mild CVS group(18 cases),moderate CVS group(39 cases),and severe CVS group(12 cases)according to the occurrence and severity of CVS detected by digital subtraction angiography at the 4th postoperative day.The levels of serum MBL,HRG,IL-23 and IL-17 among the four groups before and 3 d after surgery were compared.The patients were followed up for 6 months and divided into good prognosis group(137 cases)and poor prognosis group(58 cases)according to their prognosis.Factors influencing poor prognosis in aSAH pa-tients were analyzed by multivariate Logistic regression model.The predictive value of serum MBL,HRG,IL-23,IL-17 levels and their combined application models for poor prognosis in patients with aSAH was analyzed by receiver operating characteristic(ROC)curve.Results The incidence rate of CVS after interventional em-bolization was 35.38%in 195 patients with aSAH.3 d after surgery,the serum levels of MBL,IL-23 and IL-17 in the mild,moderate,and severe CVS groups were higher than those in the no CVS group,those in the severe CVS group were higher than those in the moderate CVS group,those in the moderate CVS group were higher than those in the mild CVS group(P<0.05).The serum HRG levels in the mild,moderate,and severe CVS groups were lower than those in the non CVS group,those in the severe CVS group were lower than those in the moderate CVS group,those in the moderate CVS group were lower than those in the mild CVS group(P<0.05).3 d after surgery,the levels of serum MBL,IL-23 and IL-17 in the four groups were higher than that before surgery,while the levels of serum HRG were lower than that before surgery(P<0.05).The pro-portions of patients with aneurysm diameter≥6 mm,number of aneurysms>1,surgery time>24 h,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,and serum levels of MBL,IL-23,and IL-17 on the 3rd day after sur-gery in the good prognosis group were lower than those in the poor prognosis group,and serum HRG levels at 3 d after surgery in the good prognosis group were higher than that in the poor prognosis group(P<0.05).Multivariate Logistic regression analysis showed that aneurysm diameter≥6 mm,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,elevated serum levels of MBL,IL-23,and IL-17 and decreased HRG level at 3 d after sur-gery were independent risk factors for poor prognosis in aSAH patients(P<0.05).ROC results showed that serum levels of MBL,HRG,IL-23,and IL-17 at 3 d after surgery had certain predictive power for poor progno-sis in patients with aSAH.The predictive model with the combined application of four indicators had relatively high efficiency(the area under the curve was 0.853).Conclusion Elevated levels of MBL,IL-23,IL-17,and decreased HRG levels in aSAH patients after interventional embolization could increase the risk of CVS and are associated with poor prognosis in aSAH patients after interventional embolization.The above indicators have a certain predictive power for poor prognosis in aSAH patients.

Objective To investigate the predictive value of serum soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)and Netrin-1 combined with acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)score for poor prognosis in patients with severe craniocerebral injury after surgery.Methods Totally 120 patients with severe craniocerebral injury admitted to a hospital from June 2020 to June 2022 were divided into good prognosis group and poor prognosis group according to the prognosis 30 days af-ter surgery.The serum levels of sTWEAK,Netrin-1 and APACHE Ⅱ score were compared between the two groups.Univariate and multivariate Logistic regression were used to analyze the influencing factors of poor prognosis in patients with severe craniocerebral injury,and the prediction model of serum sTWEAK,Netrin-1 and APACHE Ⅱ score combined was constructed.The predictive value of serum sTWEAK,Netrin-1 level and APACHE Ⅱ score in patients with severe craniocerebral injury after surgery was analyzed by receiver operat-ing characteristic(ROC)curve.Results The duration of intensive care unit stay in the poor prognosis group was longer than that in the good prognosis group,and the albumin level,Glasgow Coma scale and serum Ne-trin-1 level at admission were lower than those in the good prognosis group.The proportion of multiple brain contusion and laceration,the proportion of mechanical ventilation,APACHE Ⅱ score at admission and the lev-els of serum sTWEAK,blood creatinine and blood urea nitrogen were higher than those in the group with good prognosis,and the differences were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that multiple brain contusion and laceration,decreased Netrin-1 level,increased APACHE Ⅱscore and increased sTWEAK level at admission were risk factors for poor prognosis in patients with severe craniocerebral injury(P＜0.05).ROC curve analysis showed that the area under the curve and 95％CI of ser-um sTWEAK,Netrin-1 and APACHE Ⅱ scores were 0.742(0.552-0.925),0.731(0.488-0.963),0.714(0.502-0.911)and 0.882(0.795-0.947)respectively when the three indexes were used alone and in com-bination.Conclusion Serum sTWEAK and Netrin-1 combined with APACHE Ⅱ score have good predictive value for the poor prognosis of patients with severe craniocerebral injury after surgery,and can provide refer-ence for the formulation of clinical treatment.

This paper briefly introduces the definition, classification and significance of effect modification in epidemiological studies, summarizes the difference between effect modifier and confounders, and analyze the influence as well as the role of effect modification in epidemiological studies and Meta-analysis. In this paper, the possible scenarios of effect modification and related analysis strategy in Meta-analysis are indicated by graphics, aiming to arouse researchers' attention to effect modification. This paper also demonstrates how to identify and deal with effect modification in Meta-analysis through a study case of "Efficacy of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes", and shows the analysis process and interpretation of results of subgroup analysis and Meta-regression methods respectively. The advantages and disadvantages of these two methods are summarized to provide reference for the method selection of future research.

This paper briefly introduces the characteristics, research significance, and global reporting status of effect modification in network Meta-analysis, demonstrates the heterogeneity caused by effect modification in network Meta-analysis, and emphasizes the importance of exploring effect modification in network Meta-analysis. This paper also summarizes the normalized description and analysis strategies of effect modification in network Meta-analysis. Finally, by the case of "comparison of efficacy of three new hypoglycemic drugs in reducing body weight in type 2 diabetes patients", this paper demonstrates the realization of subgroup analysis and network Meta-regression in exploring effect modification, summarizes the advantages and disadvantages of the two methods, to provide references for future researchers.

Objective:Differences between randomized controlled trial (RCT) results and real world study (RWS) results may not represent a true efficacy-effectiveness gap because efficacy-effectiveness gap estimates may be biased when RWS and RCT differ significantly in study design or when there is bias in RWS result estimation. Secondly, when there is an efficacy- effectiveness gap, it should not treat every patient the same way but assess the real-world factors influencing the intervention's effectiveness and identify the subgroup likely to achieve the desired effect.Methods:Six databases (PubMed, Embase, Web of Science, CNKI, Wanfang Data, and VIP) were searched up to 31 st December 2022 with detailed search strategies. A scoping review method was used to integrate and qualitatively describe the included literature inductively. Results:Ten articles were included to discuss how to use the RCT research protocol as a template to develop the corresponding RWS research protocol. Moreover, based on correctly estimating the efficacy-effectiveness gap, evaluate the intervention effect in the patient subgroup to confirm the subgroup that can achieve the expected benefit-risk ratio to bridge the efficacy-effectiveness gap.Conclusion:Using real-world data to simulate key features of randomized controlled clinical trial study design can improve the authenticity and effectiveness of study results and bridge the efficacy-effectiveness gap.