Esophageal cancer （EC） is a highly prevalent malignant tumor in China. The phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， as one of the key oncogenic pathways， can promote the cell cycle progression， proliferation， migration， and invasion， induce chemoresistance， and inhibit apoptosis and autophagy of EC cells. Traditional Chinese medicine （TCM）， with the advantages of targeting multiple points with multiple components to delay cancer progression， can target the PI3K/Akt signaling pathway for EC treatment. This article preliminarily discusses the molecular mechanism and role of the PI3K/Akt signaling pathway in EC and elaborates on the specific targets and efficacy of TCM in treating EC through intervention in the PI3K/Akt signaling pathway in the past five years. TCM materials and extracts inhibiting the PI3K/Akt signaling pathway in EC include Borneolum， spore powder of Ganoderma lucidum without spore coat， extract of Celastrus orbiculatus， root extract of Taraxacum， and Bruceae Fructus oil emulsion. TCM active ingredients exerting the effect include flavonoids， terpenoids， saponins， phenols， polysaccharides， alkaloids， and other compounds. TCM compound prescriptions with such effect include Qige San， Huqi San， Xuanfu Daizhetang， Tongyoutang and its decomposed prescriptions， Liujunzi Tang， and Xishenzhi Formula. In addition， TCM injections such as Compound Kushen Injection and Kang'ai injection also inhibit the PI3K/Akt signaling pathway in EC. This paper summarizes the role of the PI3K/Akt signaling pathway in EC and the TCM interventions， aiming to provide reference for the research and clinical application of new drugs for EC.

OBJECTIVE To evaluate the efficacy and safety of immune checkpoint inhibitors （ICIs） combined with neoadjuvant chemotherapy in the treatment of early triple-negative breast cancer （TNBC）. METHODS Randomized controlled trials （RCTs） comparing ICIs combined with neoadjuvant chemotherapy （experimental group） versus neoadjuvant chemotherapy alone （control group） were retrieved from PubMed， Cochrane Library， Embase， Web of Science， CNKI， Wanfang Data， and VIP databases， as well as relevant studies published at oncology academic conferences. The search period was from database inception to June 30， 2025. After literature screening， data extraction， and quality assessment， a meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 6 RCTs involving 3 786 patients were finally included. The meta-analysis results showed that the experimental group had superior event-free survival [HR＝0.73， 95%CI （0.62， 0.85）， P＜0.000 1]， overall survival [HR＝0.69， 95%CI （0.57， 0.84）， P＝0.000 3]， and pathological complete response （pCR） [OR＝1.57， 95%CI （1.37， 1.80）， P＜0.000 01] compared to the control group. The incidence of ≥grade 3 adverse event （AE）， severe AE （SAE）， and ≥ grade 3 immune-related adverse event （irAE） in the experimental group was significantly higher than that in the control group. There was no statistically significant difference between the two groups in the incidence of any AE or any irAE （P＞0.05）. Subgroup analysis revealed that， regardless of programmed cell death ligand 1 expression status （negative or positive），the pCR in the experimental group was significantly higher than that in the control group （P＜0.05）. Additionally， the pCR of the patients with positive lymph nodes in the experimental group was significantly higher to that in the ontrol group （P＜0.05）. There was no statistically significant difference in pCR between the two groups with negative lymph nodes （P＝0.09）. CONCLUSIONS ICIs combined with neoadjuvant chemotherapy can significantly improve event-free survival and overall survival in patients with TNBC， providing patients with long-term survival benefits. However， the risk of ≥ grade 3 AE， SAE and ≥ grade 3 irAE has increased.

Left ventricular pseudoaneurysm(LVPA) is a rare type of abnormal ventricular wall bulge formed by injury to the inner wall of the left ventricle. The exterior wall only consists of epicardium or/and pericardium. In a systematic literature review, myocardial infarction(55%), surgery(33%), and trauma(7%) are the top three associations. Being affected by the high pressure of the left ventricle, LVPA has the risk of enlargement and rupture, which can lead to sudden death. The treatment of LVPA consists of three main modalities: medication, surgery, and transcatheter closure. In the past, surgery was the preferred treatment for LVPA, but the surgery was highly invasive, traumatic, and associated with increased risks. In recent years, transcatheter closure has been developed and applied clinically with good results. The benefits of minimal invasiveness and quick recovery have emerged as a popular treatment for LVPA. Currently, the etiology, formation, and treatment of LVPA are not clearly defined. Large-sample studies and authoritative guidelines to guide the treatment are scarce. The timing, imaging modality, and access routes to LVPA for both surgery and transcatheter closure are still controversial. In this article, we review the relevant literatures and draw the following conclusions as: (1) Diagnostic workup is essential for anatomical characterization of LVPA, which is mandatory to guide the decision on surgical methods.(2) For a subset of patients with LVPA and a well-defined fibrotic neck, and deemed at high surgical risk, transcatheter closure of the cavity has been described with encouraging results.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

Objective:To investigate the protective effect of fluoxetine on neurons in rats with subarachnoid hemorrhage (SAH) and explore its mechanism based on the chemokine receptor 4 (CXCR4)/nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) pathway.Methods:Seventy-five rats were randomly divided into a normal control group and a model group. The SAH model was established by the internal carotid artery puncture method in the model group. After modeling, rats were randomly divided into the model group, fluoxetine low-, medium-, and high-dose groups, and nimodipine group, with 12 rats in each group. The fluoxetine low-, medium-, and high-dose groups were intravenously injected with fluoxetine at doses of 5, 10, and 15 mg/kg, respectively; the nimodipine group was intraperitoneally injected with nimodipine at 0.2 mg/kg; the normal control group and model group were intraperitoneally injected with an equal volume of normal saline, once a day for 7 consecutive days. The shuttle box was used to determine the number of avoidance responses and avoidance response time of rats. The water content of brain tissue and Evans blue exudation volume were calculated. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in the hippocampal tissue. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal tissue. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA levels of CXCR4 and NLRP1 in the hippocampal tissue. Western blot was used to determine the protein levels of CXCR4, NLRP1, LC3-Ⅱ, and Beclin1 in the hippocampal tissue.Results:Compared with the normal control group, the model group had a lower number of avoidance responses, lower levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were higher (all P<0.05). Compared with the model group, the fluoxetine groups (all doses) and nimodipine group had a higher number of avoidance responses, higher levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were lower (all P<0.05); moreover, the changes in various indicators were more significant with the increase of fluoxetine dose. HE staining results showed that there were no pathological changes in the hippocampal tissue of the normal control group; in the model group, the number of hippocampal neurons decreased, nuclei were pycnotic, and cell arrangement was irregular. Compared with the model group, the number of hippocampal neurons increased, cell arrangement was regular, and hippocampal pathology was significantly restored in the fluoxetine groups (all doses) and nimodipine group. Conclusions:Fluoxetine can significantly alleviate the pathological progression of cerebral edema, repair neuronal damage, improve neurological function, and regulate mitochondrial autophagy in SAH rats, whose mechanism may be related to the regulation of the CXCR4/NLRP1 pathway.

Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.

Objective To evaluate the efficacy,safety and cost-effectiveness of dorzagliatin in the treatment of type 2 diabetes mellitus using a rapid health technology assessment,and to provide medical evidence for clinical decision-making.Methods PubMed,Embase,Cochrane Library,CNKI,Wanfang Data,SinoMed and relevant health technology assessment(HTA)websites and databases were searched to collect systematic reviews/Meta-analysis,pharmacoeconomic literature and HTA reports of dorzagliatin in the treatment of type 2 diabetes from inception to July 20,2024.Two reviewers independently screened literature,extracted date and assessed quality.The results were qualitatively described and analyzed.Results A total of 6 studies were included,including 5 systematic reviews/Meta-analysis and a pharmacoeconomic study.In terms of efficacy compared with placebo,dorzagliatin significantly reduced glycated hemoglobin(HbA1c),fasting plasma glucose,2-hour postprandial blood glucose and insulin resistance index(P＜0.05),improved HbA1c compliance rate in terms of safety,dorzagliatin,and enhanced homeostasis model assessment-β(P＜0.05),significantly increased total cholesterol,triglyceride,body weight and body mass index(P＜0.05).In terms of safety,the total incidence of adverse reactions of dorzagliatin was slightly higher than that of the placebo group(P＜0.05).However,there was no significant difference in the incidence of severe adverse reactions between the two groups(P＞0.05),and there was no significant increase in the incidence of hyperlipidemia and hypoglycemia(P＞0.05).In terms of economy,the treatment of dorzagliatin combined with metformin has a long-term cost-utility advantage,with an economic probability of nearly 70％.Conclusion Compared with placebo,dorzagliatin has a good overall efficacy and safety in the treatment of type 2 diabetes.In terms of safety,the total incidence of adverse reactions of dorzagliatin was slightly higher than that of placebo.In terms of economy,compared with metformin alone,dorzagliatin combined with metformin has economic advantages.However,there is a lack of head-to-head comparisons of doxorubicin with other classes of glucose-lowering medications,and none of the included studies described long-term cardiac,cerebral,or renal benefits,which limits the comprehensive evaluation of the efficacy and safety of dorzagliatin.

Objective:To evaluate the changes in brain network function indicators in premature infants with language developmental disorders by resting state functional magnetic resonance imaging (rs-fMRI).Methods:Premature infants admitted to Changzhou Children's Hospital Affiliated to Nantong University from January 2021 to December 2023 were selected as the study subjects to evaluate language development. Language development assessment was conducted using the Gesell developmental scales during follow-up until 12 months of corrected gestational age. According to the evaluation results, the subjects were divided into language development disorders group (31 cases) and normal language development group (19 cases). rs-fMRI was performed on all premature infants with corrected gestational age of 40-42 weeks. The amplitude of low frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis were performed on MRI data. Regions of interest (ROI) were obtained as seed points based on previous literature, then functional connectivity (FC) was extracted between these ROIs for inter-group comparison. Independent sample t-test, non parametric test, chi-square test, and Fisher's exact test were performed on the data using SPSS 23.0 software. Results:(1)There were statistically significant differences in birth weight, gestational age, moderate to severe respiratory distress syndrome, sepsis, and maternal education level between the two groups of premature infants (all P<0.05).(2)The FC values of left temporal gyrus-left angular gyrus (1.220±0.155, 1.139±0.118), left insula-left trigone (0.520±0.199, 0.411±0.152), and left angular gyrus-left marginal gyrus (1.588±0.333, 1.330±0.437) in language development disorders group were higher than those in normal language development group ( t=-2.089, -2.186, -2.359, all P<0.05). There was no statistically significant difference in the FC values of ROI-ROI between the two groups in the right hemisphere of the brain (all P>0.05). The FC values of left superior temporal gyrus-right insula (0.588±0.257, 0.398±0.305) and left superior temporal gyrus-right marginal gyrus (1.550±0.393, 1.374±0.213) in language development disorders group were higher than those in the normal language development group ( t=-2.363, 2.057, both P<0.05). Conclusions:Functional connectivity between local brain regions in preterm infants with language development is significantly enhanced. The change of local brain network functional connectivity has certain predictive value for the language developmental outcome of preterm infants.

Objective To evaluate the safety and efficacy of ciprofol in the anesthesia of elderly patients undergoing bronchoscopy.Methods A total of 96 elderly patients(≥65 years old)undergoing fiberoptic bronchos-copy under sedation and anesthesia were randomly assigned to either the ciprofol group(Group C,n=48)or the propofol group(Group P,n=48).In Group C,anesthesia was induced with an intravenous injection of sufentanil at 0.1 μg/kg and ciprofol at 0.3 mg/kg.In Group P,anesthesia was induced with an intravenous injection of sufent-anil at 0.1 μg/kg and propofol medium/long-chain fat emulsion at 1.5 mg/kg.Hemodynamic parameters,including heart rate(HR),mean arterial pressure(MAP),and peripheral oxygen saturation(SpO2),were recorded at five time points:before anesthesia induction(T1),immediately after the bronchoscope passed through the glottis(T2),immediately after it reached the carina(T3),immediately after the bronchoscope was withdrawn from the nostril post-procedure(T4),and upon full consciousness after leaving the recovery room(T5).Additionally,the success rate of sedation and anesthesia,cough severity scores,induction time(t1),bronchoscopy duration(t2),recovery time(t3),and orientation recovery time(t4)were documented for both groups.Intraoperative complications,such as hypotension,hypoxemia(SpO2<90%),injection pain during induction,airway interventions(e.g.,jaw support,mask ventilation),and the number of additional sedative doses administered,were also recorded.Results Compared with T1,MAP in both groups decreased at T2 and T3(P<0.05).Compared with group P,group C exhibited a higher MAP at T2 and T3(P<0.05).between the two groups in terms of sedation success rate,induction time,cough score,examination time,recovery time,and orientation recovery time(P>0.05).Compared with group P,group C demonstrated lower incidences of hypotension,hypoxemia,injection pain,and fewer airway intervention events(P<0.05).Conclusions Compared with propofol,ciprofol in combination with sufentanil demonstrates superior circulatory stability,a lower incidence of respiratory system-related adverse reactions,and reduced injection pain.Therefore,it can be safely and effectively utilized for painless bronchoscopic diagnosis and treatment in elderly patients.