ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

Objective: To characterize perioperative dynamic changes in immune-cell phenotypes and inflammatory cytokines in patients undergoing CPB (cardiopulmonary bypass) cardiac surgery, and to explore their associations with postoperative outcomes. Methods: In this prospective cohort study, 120 adult patients who underwent elective cardiac surgery under CPB at West China Hospital from May 2022 to March 2023 were enrolled. Perioperative immune-cell phenotypes and concentrations of 40 inflammation-related cytokines were measured. The primary outcomes were the sequential organ failure assessment (SOFA) score at 24 h after surgery and ΔSOFA (the peak SOFA score within 48 h after surgery minus the preoperative SOFA score). Secondary outcomes included major adverse cardiovascular events (MACE), acute kidney injury (AKI), respiratory failure, severe liver injury, and infection. Results: The mean age of enrolled patients was 57±10 years. Of these, 52% (62/120) were male and 90% (108/120) underwent valve surgery. During the rewarming to the end of CPB, neutrophil counts rapidly increased (7.39×10 /L vs preoperative 3.07×10 /L, P<0.001), with significant upregulation of CD11b (7.30×10 /L vs preoperative 3.05×10 /L, P<0.001) and CD54 (7.15×10 /L vs preoperative 2.99×10 /L, P<0.001). Lymphocyte counts increased at the end of CPB (1.75×10 /L vs preoperative 1.12×10 /L, P<0.001) but decreased significantly at 24 h after surgery (0.59×10 /L vs preoperative 1.12×10 /L, P<0.001). Plasma analysis showed that multiple pro-inflammatory cytokines increased during CPB and remained elevated up to 24 h after surgery; five chemokines and the anti-inflammatory cytokine IL-10 peaked at the end of CPB. The SOFA score increased from 1 (1, 2) preoperatively to 7 (5, 10) at 24 h after surgery, with a ΔSOFA of 6 (4, 8). Within 30 days after surgery, 48 patients (40.0%) developed AKI, 17 (14.2%) developed infection, 4 (3.3%) developed severe liver injury, 3 (2.5%) developed respiratory failure, and 3 (2.5%) experienced MACE. During the 2-year follow-up, 8 patients (6.7%) experienced MACE and 5 (4.2%) died. Conclusion: Multi-organ dysfunction is common after cardiac surgery under CPB (median ΔSOFA, 6), accompanied by perioperative activation of multiple immune-cell subsets and upregulation of pro-inflammatory, anti-inflammatory, and chemotactic mediators. This study provides data-driven evidence and research clues for further investigation of the associations between CPB-related immune perturbations and postoperative organ dysfunction and clinical outcomes.

Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveTo explore the effect of Polygonati Odorati Rhizoma polysaccharides on hyperlipidemia in mice by modulating the gut microbiota. MethodsNinety male C57BL/6J mice were randomized into the following groups （n=15）： control， model， simvastatin， low- （100 mg·kg^-1）， medium- （200 mg·kg^-1）， and high-dose （400 mg·kg^-1） Polygonati Odorati Rhizoma polysaccharides groups. Other groups except the control group were fed with a high-fat diet for the modeling of hyperlipidemia， and drug interventions lasted for 12 weeks. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） were measured by an automatic biochemical analyzer. The pathological changes in the liver and epididymal fat were observed by hematoxylin-eosin staining， and lipid accumulation in the liver was assessed by oil red O staining. The gut microbiota was analyzed by 16S rRNA gene sequencing. ResultsCompared with the control group， the model group exhibited an increase in body weight （P<0.01）， along with marked elevations in serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）. Furthermore， the model group showcased increase in the liver index and epididymal fat coefficient （P<0.05）， increased liver fat accumulation， enlargement of adipocytes in the epididymal fat， decreases in both alpha and beta diversity of the gut microbiota， and an increase in the relative abundance of Allobaculum （P<0.01）. Compared with the model group， Polygonati Odorati Rhizoma polysaccharides suppressed the increase in body weight （P<0.01）， lowered the serum levels of TC， TG， and LDL-C （P<0.05，P<0.01）， reduced the liver index and epididymal fat coefficient （P<0.05）， alleviated liver fat accumulation， and decreased the size of adipocytes in the epididymal fat. Furthermore， it enhanced the alpha and beta diversity of the gut microbiota in mice， reduced the relative abundance of Allobaculum， Erysipelotrichaceae， and Clostridium （P<0.01）， and increased the relative abundance of Akkermansia and Blautia （P<0.01）. ConclusionPolygonati Odorati Rhizoma polysaccharides can ameliorate hyperlipidemia induced by a high-fat diet in mice by regulating the diversity and composition of the gut microbiota.

Objective:To investigate the clinical efficacy of a self-detachable single-J internal stent drainage tube in the laparoscopic primary suture of the common bile duct for hepatolithiasis.Methods:Clinical data of 36 patients with hepatobiliary duct stones who underwent laparoscopic common bile duct primary suture combined with self-detached single J-type internal stent drainage at the First Affiliated Hospital of Xiamen University from April 2022 to April 2025 were retrospectively analyzed, including 17 males and 19 females, aged (54.3±8.7) years. All 36 patients underwent choledochoscopic stone extraction, primary common bile duct suture, and drainage with the self-expelling single-J internal stent. Total bilirubin, aspartate transaminase, and alanine transaminase before and 3 days after operation, as well as operation time, intraoperative blood loss, postoperative hospital stay, postoperative complications (bile leakage, cholangitis, intestinal obstruction, and stent retention), and stent expulsion time were collected.Results:All 36 patients successfully underwent the operation. Total bilirubin, aspartate transaminase, and alanine transaminase 3 days after operation showed significant improvement compared to preoperative levels (all P<0.05). The operation time was (86.5±22.6) min, intraoperative blood loss was 34.2 (13.7, 56.8) ml, and the postoperative hospital stay was (6.6±1.8) days. All single-J internal stents were spontaneously expelled via the anus between 6 and 21 days postoperatively, with the expulsion time of (10.7±2.1) days. No single J-type internal stent drainage tube was displaced into the bile duct in all cases, and there were no complications such as intestinal obstruction, bile leakage, cholangitis, or residual internal stent drainage tube. Conclusion:The self-detachable single-J internal stent drainage tube has been applied in the laparoscopic primary suture of the common bile duct for patients with hepatolithiasis, which demonstrated a good safety and effectiveness.

Objective:To investigate the clinical efficacy of a self-detachable single-J internal stent drainage tube in the laparoscopic primary suture of the common bile duct for hepatolithiasis.Methods:Clinical data of 36 patients with hepatobiliary duct stones who underwent laparoscopic common bile duct primary suture combined with self-detached single J-type internal stent drainage at the First Affiliated Hospital of Xiamen University from April 2022 to April 2025 were retrospectively analyzed, including 17 males and 19 females, aged (54.3±8.7) years. All 36 patients underwent choledochoscopic stone extraction, primary common bile duct suture, and drainage with the self-expelling single-J internal stent. Total bilirubin, aspartate transaminase, and alanine transaminase before and 3 days after operation, as well as operation time, intraoperative blood loss, postoperative hospital stay, postoperative complications (bile leakage, cholangitis, intestinal obstruction, and stent retention), and stent expulsion time were collected.Results:All 36 patients successfully underwent the operation. Total bilirubin, aspartate transaminase, and alanine transaminase 3 days after operation showed significant improvement compared to preoperative levels (all P<0.05). The operation time was (86.5±22.6) min, intraoperative blood loss was 34.2 (13.7, 56.8) ml, and the postoperative hospital stay was (6.6±1.8) days. All single-J internal stents were spontaneously expelled via the anus between 6 and 21 days postoperatively, with the expulsion time of (10.7±2.1) days. No single J-type internal stent drainage tube was displaced into the bile duct in all cases, and there were no complications such as intestinal obstruction, bile leakage, cholangitis, or residual internal stent drainage tube. Conclusion:The self-detachable single-J internal stent drainage tube has been applied in the laparoscopic primary suture of the common bile duct for patients with hepatolithiasis, which demonstrated a good safety and effectiveness.

Objective To develop a Nomogram clinical prediction model for the pathological occurrence of extraprostatic extension(EPE)after radical prostatectomy in prostate cancer patients,using simplified site-specific magnetic resonance imaging(MRI)indicators and other clinical parameters.Methods A total of 181 prostate cancer patients[mean age(69.0±7.3)years]who underwent radical prostatectomy were included.These patients had received 3-Tesla multi-parametric magnetic resonance imaging(3-T mpMRI)within 6 months prior to surgery.Based on mpMRI measurements[capsular contact length(CCL)>15 mm,capsular bulging/irregularities,diameter of index lesion(dIL),and evident extraprostatic extension(eEPE)],the dIL?sEPE grading system was derived.The optimal cut-off value of dIL(denoted as dIL)was determined using the Youden J index,and categorized it into a binary variable.A Logistic regression model was established based on the dIL?sEPE grading and clinical scores.The predictive performance of clinical indicators,MRI indicators,and combined clinical and MRI indicators were compared.Finally,a clinical prediction model integrating both clinical and MRI data was developed.Results Pathological EPE was found in 46 out of 181 cases(25.4% ).A Nomogram prediction model for EPE was established with a combination of the dIL?sEPE grading and clinical indicators.Conclusion The combination of dIL?sEPE grading with clinical indicators accurately predicts extracapsular extension in prostate cancer.The Nomogram model that established,based on MRI imaging characteristics and clinical indicators has good performance and is easy to use.It is beneficial to stratifying management for prostate cancer patients,and it provides valuable guidance for patients suitable for nerve-sparing surgery.

Both the androgen receptor pathway and PI3K/AKT pathway play pivotal roles in the progression of prostate cancer.There are intricate interactions between these two pathways,showing a negative regulatory relationship of mutual restriction between them.In view of the above,a combined inhibition strategy targeting these two pathways is expected to become a significant therapeutic approach for prostate cancer.This article aims to comprehensively review the molecular mechanisms underlying the interactions between the androgen receptor and PI3K/AKT pathways,to provide new perspectives and insights for research in the fields.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

AIM:This study aims to investigate the impact of TWIK-1 channels on abnormal pacemaker activi-ties induced by hypokalemia and to elucidate the underlying mechanisms.METHODS:The gene sequences encoding hu-man TWIK-1,specific TWIK-1 shRNA and TWIK-1-T118i mutant were synthesized and subsequently subcloned into lenti-viral vectors.To knock down the TWIK-1 gene in human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs),the cells were transduced with lentivirus carrying the specific TWIK-1 shRNA sequences.For the overexpression of TWIK-1 or the TWIK-1-T118i mutant in HL-1 mouse cardiomyocytes,the cells received lentiviral transduction containing the respective gene sequences.Patch-clamp techniques were employed to assess the effects of 1 mmol/L extracellular K+on the membrane potentials and whole-cell currents of the cardiomyocytes.RESULTS:Under conditions of 1 mmol/L extra-cellular K+,depolarization of membrane potentials was observed in the hiPSC-CMs and the HL-1 mouse cardiomyocytes ex-pressing human TWIK-1 channel,leading to the induction of abnormal pacemaker activities.This phenomenon could be reversibly abolished by the removal of extracellular Na+or inhibited through TWIK-1 knockdown.In contrast,the mem-brane potentials of HL-1 mouse cardiomyocytes expressing human TWIK-1-T118i mutant hyperpolarized,with no occur-rence of abnormal pacemaker activities.The hiPSC-CMs exhibiting abnormal pacemaker activities at 1 mmol/L extracellu-lar K+demonstrated TWIK-1-like Na+leak currents,which were blocked by quinine,a non-selective blocker of TWIK-1.CONCLUSION:The TWIK-1 channels play a critical role in the development of hypokalemia-induced abnormal pace-maker activities in human cardiomyocytes by facilitating Na+leak currents.