Background: Patients with coarctation of the aorta (CoA) and an interrupted aortic arch (IAA) may present with small mitral valves (MVs) and a reduced left ventricular (LV) volume. Biventricular repair (BVR) in these patients is dependent on adequate size of the left cardiac structures.Purpose: This study evaluated the impact of the hemodynamic characteristics of atrial septal defects (ASDs) on MV growth following surgical repair. Methods: We retrospectively reviewed the data of patients diagnosed with CoA or IAA between 2007 and 2024. The z score for MV size measured 6 months postoperatively (Z2) was compared with the preoperative MV size (Z1). The factors associated with MV growth were also studied. Results: A total of 161 patients with CoA or IAA were included. Transthoracic echocardiography was used to assess the MV and LV dimensions preoperatively and 6 months postoperatively. Of the cohort, 155 (96.3%) underwent initial BVR and 6 underwent single-ventricle palliation. MV z scores significantly increased following BVR (mean change: +0.45±1.35; P<0.001) but decreased after single-ventricle repair (-0.56±0.49, P=0.04). Multivariate analysis identified the initial MV z score and ASD pressure gradient as independent predictors of MV growth (R2=0.39). Conclusion Annular growth of the MV was not observed in patients who underwent single-ventricle palliation. In contrast, among patients who achieved BVR, those with a small preoperative MV annulus and low ASD pressure gradient demonstrated subsequent catch-up MV growth, suggesting that adequate left-sided preload is essential for MV development.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of toripalimab （Tor） combined with chemotherapy （CT） in the treatment of locally advanced or metastatic non-small cell lung cancer （NSCLC）. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CBM， CNKI， Wanfang Data， and Health Technology Assessment （HTA） related websites were searched to collect the HTA reports， systematic reviews/meta-analyses and pharmacoeconomic studies of Tor+CT in the treatment of locally advanced or metastatic NSCLC from database/website inception to March 31， 2025. After data extraction and quality evaluation， the results of the included studies were analyzed descriptively. RESULTS A total of eleven studies were included， involving five systematic reviews/meta-analyses， and six pharmacoeconomic studies. Among the five systematic reviews/ meta-analyses， two were of high quality， while there was one each of moderate， low， and very low quality. All six pharmacoeconomic studies were of good quality. In terms of efficacy， compared with CT， Tor+CT significantly improved patients’ progression-free survival （PFS） and overall survival （P＜0.05）. In addition， compared with ipilimumab+CT， durvalumab， durvalumab+tremelimumab and sugemalimab+CT， Tor+CT could also improve the PFS （P＜0.05）. In terms of safety， there was no significant difference in the incidence of grade≥3 adverse events between patients receiving Tor+CT and CT （P＞0.05）； while Tor+CT had a lower incidence of grade≥3 adverse E-mail： events， compared with camrelizumab+CT， pembrolizumab+ 3233255290@qq.com ipilimumab， nivolumab+CT and atezolizumab+CT （P＜0.05）.In terms of cost-effectiveness， Tor+CT treatment had certain cost-effectiveness advantages， compared with CT. CONCLUSIONS Compared with CT， other programmed death-1/programmed death-ligand 1 inhibitors alone， or their combination with CT， Tor+CT for the treatment of locally advanced or metastatic NSCLC has good efficacy， safety and cost-effectiveness.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.

Aim To explore the action mechanism of isoquercitrin(IQ)in ameliorating anxiety based on network pharmacology,cellular transcriptomics,molecu-lar docking and animal experiments.Methods The common targets of anxiety disorders and IQ were ob-tained by using relevant databases.The protein-protein interaction network,the biological function and signa-ling pathway enrichment analysis were conducted by u-sing the common targets.Primary hippocampal neurons were cultured in vitro,and corticosterone was added to induce neurons to establish a corticosterone injury mod-el.IQ treatment was added to the culture system,and transcriptomics was used to screen for differentially ex-pressed genes and enrich for differentially expressed pathways.Subsequently,the results were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Possible targets and signaling pathways for IQ treatment on anxiety were speculated and screened u-sing network pharmacology,transcriptomics and molec-ular docking.The anxiety rat model was constructed,and the anxiety state of rats was evaluated after IQ in-tervention,and the protein expression level of hippo-campus was detected to verify the relevant mechanism.Results Network pharmacology,cellular transcrip-tome,and molecular docking analyses revealed that the key mechanism of IQ for anxiety may be related to the BDKRB2/PI3K/Akt signaling pathway.Animal exper-iments showed that IQ was effective in improving anxie-ty behaviour and learning memory ability in rats.IQ increased the movement distance and residence time in the central area of the open field,the time and number percentage of entries into the open arm in the elevated plus maze,and the spontaneous alternations score in the Y maze in rats,and significantly elevated protein expression of BDKRB2,PI3K,Akt and decreased pro-tein expression of NF-κB in the hippocampus.Conclu-sions Isoquercitrin can effectively treat anxiety,and the mechanism of action may be related to the regula-tion of BDKRB2/PI3K/Akt signaling pathway in hip-pocampus.

Objective:To systematically evaluate the clinical outcomes of hemihepatic inflow occlusion(HHO)and total hepatic inflow occlusion(THO)in liver resection surgery.Method:Re-trieve the Cochrane Library,PubMed,EMbase,Ovid,Web of Science,CNKI,and WanFang Data databases,and search for journal articles published from January 1,2000 to January 31,2023,on randomized controlled trials(RCTs)comparing the effects of HHO and THO in liver resection.At the same time,two researchers independently screened literature based on inclusion and exclusion cri-teria,conducted meta-analysis using RevMan 5.4 and State17PM software.Result:Fifteen RCTs were ultimately included,including 624 patients.The meta-analysis results showed that HHO re-duced serum AST(MD=-104.75,95％CI:-134.45-75.06,P＜0.05),ALT(MD=-155.37,95％CI:-182.90-127.85,P＜0.05),and TBIL(MD=-6.28,95％CI:-8.07-4.48,P＜0.05)on postoperative days 1,3,and 7 Compared to THO,the elevation of blood levels and reduction of intraoperative bleeding(MD=-66.21,95％CI:-116.49-15.94,P＜0.05)were superior.THO is superior to HHO in shortening surgical time(MD=13.94,95％CI:4.77-23.12,P＜0.05).There was no significant differ-ence between the two methods in hospital stay,hospital death rate and complication rate(P＞0.05).Conclusion:compared with THO,the application of HHO in hepatectomy has less damage to liver function and less intraoperative bleeding,but the two methods have the similar effect in terms of hospitalization time,hospital mortality rate and complication rate.

Objective:To systematically evaluate the clinical outcomes of hemihepatic inflow occlusion(HHO)and total hepatic inflow occlusion(THO)in liver resection surgery.Method:Re-trieve the Cochrane Library,PubMed,EMbase,Ovid,Web of Science,CNKI,and WanFang Data databases,and search for journal articles published from January 1,2000 to January 31,2023,on randomized controlled trials(RCTs)comparing the effects of HHO and THO in liver resection.At the same time,two researchers independently screened literature based on inclusion and exclusion cri-teria,conducted meta-analysis using RevMan 5.4 and State17PM software.Result:Fifteen RCTs were ultimately included,including 624 patients.The meta-analysis results showed that HHO re-duced serum AST(MD=-104.75,95％CI:-134.45-75.06,P＜0.05),ALT(MD=-155.37,95％CI:-182.90-127.85,P＜0.05),and TBIL(MD=-6.28,95％CI:-8.07-4.48,P＜0.05)on postoperative days 1,3,and 7 Compared to THO,the elevation of blood levels and reduction of intraoperative bleeding(MD=-66.21,95％CI:-116.49-15.94,P＜0.05)were superior.THO is superior to HHO in shortening surgical time(MD=13.94,95％CI:4.77-23.12,P＜0.05).There was no significant differ-ence between the two methods in hospital stay,hospital death rate and complication rate(P＞0.05).Conclusion:compared with THO,the application of HHO in hepatectomy has less damage to liver function and less intraoperative bleeding,but the two methods have the similar effect in terms of hospitalization time,hospital mortality rate and complication rate.

Hepatocellular carcinoma is one of the most common malignant tumors worldwide, posing a great threat to human health and life. Despite the tremendous progress in understanding the origin and molecular characterization of hepatocellular carcinoma, there are still few therapeutic options that can significantly increase the survival rate and improve the quality of life of patients. Protein post-translational modifications (PTMs) are regulatory mechanisms for protein activity, localization, expression, and interactions with other cellular molecules that induce changes in protein properties and functions. More and more studies have demonstrated that PTMs and immunotherapy play an important role in the development of hepatocellular carcinoma, even in the immunosurveillance of hepatocellular carcinoma and the treatment and prognosis of hepatocellular carcinoma patients. Traditional types of PTMs include phosphorylation, glycosylation, methylation, and ubiquitination. Phosphorylation affects cancer development and progression by regulating tumor cell proliferation, invasion and metastasis, and inhibiting apoptosis. There are two main types of glycosylation: O-glycosylation andN-glycosylation. Abnormal glycosylation not only promotes the proliferation and metastasis of hepatocellular carcinoma cells, but also plays an important role in immune recognition and immune escape. Common methylation modifications include DNA methylation, RNA methylation and histone methylation. Among them, histone methylation, as an important epigenetic regulatory mechanism, is of great theoretical and practical significance for understanding the mechanism of hepatocellular carcinoma as well as carrying out the corresponding prevention and immunotherapy. Ubiquitination plays an important role in the localization, metabolism, function, regulation and degradation of proteins, and it is regulated at different levels by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin-conjugating enzyme (E3), and a series of deubiquitinating enzymes (DUBs) and is closely related to hepatocellular carcinoma immunotherapy. This paper begins with a brief overview of the importance of PTMs of proteins, discusses the importance of these traditional types of PTMs in hepatocellular carcinoma immunotherapy, and summarizes the most recent applications of these approaches in hepatocellular carcinoma in order to explore the mechanism of action of PTMs in hepatocellular carcinoma immunotherapy. Then, we summarize the finding that programmed death-ligand 1 (PD-L1) is associated with a variety of conventional types of PTMs, that in-depth study of the mechanisms regulating PD-L1 expression in tumor cells is expected to improve therapeutic efficacy, and that targeting PD-L1 in PTMs is expected to be a new field for exploring hepatocellular carcinoma immunotherapy in the future. Finally, we discuss the current status of research on PTMs for hepatocellular carcinoma immunotherapy and provide new insights and future research directions. In addition to the traditional types of PTMs, multiple novel PTMs have also been identified in published research reports, while the relationship between novel PTMs and hepatocellular carcinoma and the types of PTMs to other undiscovered proteins are still poorly understood, and future research will be focused on a more comprehensive knowledge and understanding of PTMs as well as on exploring new types and mechanisms of PTMs. Overall, further investigation of the role of PTMs in tumor immunity could help to discover new biomarkers and to develop more effective and personalized cancer immunotherapies and targeted therapies, expanding our understanding of cancer biology.

Objectives: Bipolar hemiarthroplasty is commonly performed to treat displaced femoral neck fractures in osteo porotic patients. This study aimed to assess the occurrence and outcomes of unplanned return visits to the emergency department (ED) within 90 days following bipolar hemiarthroplasty for displaced femoral neck fractures. Methods: The clinical data of 1322 consecutive patients who underwent bipolar hemiarthroplasty for osteoporotic femoral neck fractures at a tertiary medical center were analyzed. Data from the patients’ electronic medical records, including demographic information, comorbidities, and operative details, were collected. The risk factors and mortality rates were analyzed. Results: Within 90 days after surgery, 19.9% of patients returned to the ED. Surgery-related reasons accounted for 20.2% of the patient’s returns. Older age, a high Charlson comorbidity index score, chronic kidney disease, and a history of cancer were identified as significant risk factors for unplanned ED visits. Patients with uncemented implants had a significantly greater risk of returning to the ED due to periprosthetic fractures than did those with cemented implants (P = 0.04). Patients who returned to the ED within 90 days had an almost fivefold greater 1-year mortality rate (15.2% vs 3.1%, P < 0.001) and a greater overall mortality rate (26.2% vs 10.5%, P < 0.001). Conclusions This study highlights the importance of identifying risk factors for unplanned ED visits after bipolar hemiarthroplasty, which may contribute to a better prognosis. Consideration should be given to the use of cemented implants for hemiarthroplasty, as uncemented implants are associated with a greater risk of peri prosthetic fractures.

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Animals ; Mice ; Disease Models, Animal ; Cerebellar Nuclei ; Autistic Disorder/pathology* ; Neurons/metabolism* ; Mutation ; Nerve Tissue Proteins/metabolism* ; Male ; Membrane Proteins ; Cell Adhesion Molecules, Neuronal