Introduction: As the most common postoperative complication, intestinal adhesions can cause intestinal obstruction, female infertility, and even endanger life. The currently developed materials for preventing intestinal adhesions mainly focus on physical barriers and reducing inflammatory reactions, while neglecting the importance of effectively promoting rapid repair of the peritoneum. We previously found that platelet-rich fibrin (PRF) can prevent postoperative intestinal adhesions. The proliferation of mesothelial cells may play a significant role in reducing intestinal adhesions, but the mechanism remains unclear. A study found a positive correlation between calretinin (CR) and mesothelial cell proliferation. Does CR play an important role in PRF promoting mesothelial cell proliferation? This study aims to further explore the mechanism of PRF in preventing intestinal adhesions. Methods: Primary mouse peritoneal mesothelial cells and mouse peritoneal fibroblasts were used in this study. The effects of PRF on the proliferation and attachment of mesothelial cells and fibroblasts were observed and compared using the CCK-8 assay, Edu assay, and laser scanning confocal microscope. The effects of PRF on the migration of mesothelial cells were examined using scratch and transwell migration assays. The effects of PRF on the mesothelial-mesenchymal transition (MMT) of mesothelial cells were examined using western blot. The expression level of CR in mesothelial cells was detected through immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot. Results: PRF promotes mesothelial cell proliferation from 1st day and significantly promotes fibroblast proliferation from 7th day. Meanwhile, PRF tends to promote the proliferation and attachment of mesothelial cells rather than fibroblasts. However, PRF had a limited regulatory effect on the MMT of mesothelial cells. In addition, PRF can promote mesothelial cell migration and upregulate the expression level of CR. Conclusion: PRF promotes mesothelial cell proliferation and migration, as well as peritoneal repair, by up-regulating CR in the early stages of peritoneal injury to prevent postoperative intestinal adhesion. Its mechanism is obviously different from that of traditional anti-adhesion materials, which will provide new strategies for the prevention of intestinal adhesions.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited response to gemcitabine-based chemotherapy. Chemoresistance in PDAC arises from both cancer-intrinsic mechanisms and extrinsic factors like stromal fibrosis. This study investigates the role of mesothelin (MSLN) and the YAP1 inhibitor TED-347 in modulating gemcitabine resistance. Elevated MSLN expression in PDAC correlates with advanced disease stages and poor prognosis. Mechanistically, MSLN promotes gemcitabine resistance by counteracting drug-induced apoptosis and upregulating ABCC1, a key drug efflux transporter. YAP1 transcriptionally activates MSLN by binding to its promoter, independent of the Canscript sequence. The YAP1 inhibitor TED-347 disrupts this interaction, reducing MSLN expression and suppressing PDAC cell migration, invasion, and epithelial-mesenchymal transition (EMT). In a mouse model, TED-347 combined with gemcitabine enhanced antitumor efficacy, reduced fibrosis, and increased gemcitabine sensitivity. Notably, TED-347 alleviated stromal fibrosis by inhibiting pancreatic stellate cell (PSC) activation, addressing a critical barrier to drug delivery. While gemcitabine itself induces fibrosis, TED-347 mitigates this effect, offering a dual therapeutic strategy. These findings highlight the YAP1-MSLN axis as a key driver of chemoresistance and fibrosis in PDAC, with TED-347 demonstrating potential to improve clinical outcomes by targeting both malignant and stromal components. This study provides a translational research framework for combining YAP1 inhibitors with chemotherapy to overcome resistance in PDAC.

AIMS:Pancreatic ductal adenocarcinoma (PDAC) develops therapy resistance primarily through its fibrotic stroma generated by activated pancreatic stellate cells (PSCs). While the lipid droplet protein perilipin 5 (PLIN5) may be associated with PSC quiescence, its precise role in PDAC pathogenesis remains unclear. This study aims to investigate PLIN5 role in regulating PSC function and tumor progression. METHODS:PLIN5 expression was analyzed in human PDAC tissue using immunohistochemistry and immunofluorescence. Primary and immortalized PSCs were used, and PLIN5 overexpression PSCs were created using lentiviral transfection. Subcutaneous and orthotopic pancreatic cancer models in nude mice were developed by using these PSCs and pancreatic cancer cells. Cytological assays, PCR, Western blotting and histological and immunofluorescence analysis, were performed to investigate PLIN5 expression in PSCs and its effects on PSC activation, fibrosis, and cancer progression. KEY FINDINGS:PLIN5 expression was markedly reduced in human PDAC tissues compared to normal adjacent pancreas and was specifically co-localized with α-SMA-positive stromal PSCs. PLIN5 expression is high in quiescent PSCs but is rapidly lost upon activation. PLIN5 inhibited PSC proliferation and migration, reduced extracellular matrix protein secretion, and restored lipid droplets formation. In vitro, PLIN5 overexpression PSCs significantly constrained the growth and invasive capacity of pancreatic cancer cells, while in vivo, they markedly reduced tumor growth and fibrosis, and prevented splenic metastasis. SIGNIFICANCE:These findings suggest that PLIN5 is a core regulatory protein that inhibits the activation of PSCs and alleviates pancreatic fibrosis, as well as a key protein in hindering pancreatic cancer progression.

OBJECTIVE:To present a global overview of the current research landscape and emerging trends in mechanical thrombectomy for acute ischemic stroke (AIS) over the past decade. METHODS:A thorough search was conducted on the Web of Science on May 20, 2024, focusing on original articles and reviews in English. Bibliometric tools were employed to make a network analysis and visual representation. Additionally, data on disability-adjusted life years, prevalence, and incidence of ischemic strokes were extracted from the Global Burden of Disease database. RESULTS:A total of 7776 papers were included, indicating a steady increase from 169 to 1311 between 2014 and 2023. The United States led in core publications with 2887 papers. The incidence and disability-adjusted life years of ischemic stroke have continued to rise in Asia but have recently declined in North America and European countries. The University of Calgary emerged as the leading institution and Mayank Goyal was the most prolific author. Neurointerventional Surgery was the top contributing journal with 790 articles. The analysis identified 6332 keywords forming 5 clusters, with "mechanical thrombectomy" serving as the largest cluster, focusing mainly on interventional thrombectomy techniques for AIS. The term "tissue plasminogen activator" exhibited strong burst strength of 46.58. Keywords such as "injury", "diagnosis", "posterior circulation", and "severity" burst in 2020 and lasted until 2024. CONCLUSIONS:Interest in mechanical thrombectomy for AIS was progressively increasing. Future research directions may include minimizing intraoperative injuries, refining diagnostic techniques, investigating interventions for posterior circulation, and tailoring thrombectomy strategies based on stroke severity and large vessel occlusion etiology.

Matrix metalloproteinase 11 (MMP11), a zinc-dependent endopeptidase involved in extracellular matrix degradation and remodeling, has been identified as a tumor promoter in multiple cancer types. However, its expression pattern and role in pancreatic ductal adenocarcinoma (PDAC) remain unclear. In this study, elevated MMP11 expression was identified in PDAC tissues and was associated with diminished survival. Integrated single-cell RNA sequencing and co-immunofluorescence staining revealed that MMP11 was predominantly expressed in cancer-associated fibroblasts (CAFs). Mechanistically, cancer cell-derived TGF-β1 mediated CAF activation via the pSmad2/3 pathway and accompanied by MMP11 production. Additionally, MMP11 knockdown in CAFs impaired the proliferative and invasive abilities of AsPC-1 and BxPC-3 cells in vitro; which could be rescued by adding recombinant MMP11. Similarly, co-injection of AsPC-1 cells with MMP11-knockdown CAFs into nude mice significantly suppressed tumor growth and liver metastasis compared with tumors bearing unmodified CAFs. Furthermore, we confirmed that CAF-derived MMP11 may drive the epithelial-mesenchymal transition process of PDAC cells to promote tumor invasion via the PI3K/AKT pathway rather than extracellular matrix remodeling. Collectively, we uncovered a crosstalk between cancer cells and CAFs mediated by TGF-β1 and MMP11 that drives the progression of PDAC.

Chemoresistance is one of the main reasons for poor prognosis of pancreatic cancer. The effects of mesothelin (MSLN) on chemoresistance in pancreatic cancer are still unclear. We aim to investigate potential roles of MSLN in chemoresistance and its relationship with proliferation, epithelial-mesenchymal transition (EMT) and cancer stemness of pancreatic cancer cells. Human pancreatic cancer cell lines ASPC-1 and Mia PaCa-2 with high and low expression of MSLN, respectively, were selected. The ASPC-1 with MSLN knockout (KO) and Mia PaCa-2 of MSLN overexpression (OE) were generated. The effects of MSLN on cell phenotypes, expression of EMT-related markers, clone formation, tumor sphere formation, and pathologic role of MSLN in tumorigenesis were detected. Sensitivity of tumor cells to gemcitabine was evaluated. The results showed that adhesion, proliferation, migration and invasion were decreased significantly in ASPC-1 with MSLN KO, whereas increased significantly in Mia PaCa-2 with MSLN OE. The size and the number of clones and tumor spheres were decreased in ASPC-1 with MSLN KO, and increased in Mia PaCa-2 with MSLN OE. In xenograft model, tumor volume was decreased (tumor grew slower) in MSLN KO group compared to control group, while increased in MSLN OE group. Mia PaCa-2 with MSLN OE had a higher IC50 of gemcitabine, while ASPC-1 with MSLN KO had a lower IC50. We concluded that MSLN could induce chemoresistance by enhancing migration, invasion, EMT and cancer stem cell traits of pancreatic cancer cells. Targeting MSLN could represent a promising therapeutic strategy for reversing EMT and chemoresistance in pancreatic cancer cells.

Background: In the past quite a long time, intraoperative cholangiography（IOC）was necessary during laparoscopic cholecystectomy (LC). Now magnetic resonance cholangiopancreatography (MRCP) is the main method for diagnosing common bile duct stones (CBDS). Whether MRCP can replace IOC as routine examination before LC is still inconclusive. The aim of this study was to analyze the clinical data of patientsundergoing LC for cholecystolithiasis, and to explore the necessity and feasibility of preoperative routine MRCP in patients with cholecystolithiasis. Methods: According to whether MRCP was performed before operation, 184 patients undergoing LC for cholecystolithiasis in the Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University from January 1, 2017 to December 31, 2018 were divided into non-MRCP group and MRCP group for this retrospective study. The results of preoperative laboratory test, abdominal ultrasound and MRCP, biliary related comorbidities, surgical complications, hospital stay and hospitalization expenses were compared between the two groups. Results: Among the 184 patients, there were 83 patients in non-MRCP group and 101 patients in MRCP group. In MRCP group, the detection rates of cholecystolithiasis combined with CBDS and common bile duct dilatation by MRCPwere higher than those by abdominal ultrasound ( P < 0.05). The incidence of postoperative complications in non-MRCP group (8.43%) was significantly higher ( P < 0.05) than that in MRCP group (0%). There was no significant difference in hospital stay ( P > 0.05), but there was significant difference in hospitalization expenses ( P < 0.05) between the two groups. According to the stratification of gallbladder stone patients with CBDS, hospital stay and hospitalization expenses were compared, and there was no significant difference between the two groups ( P > 0.05). Conclusions: The preoperative MRCP can detect CBDS, cystic duct stones and anatomical variants of biliary tract that cannot be diagnosed by abdominal ultrasound, which is helpful to plan the surgical methods and reduce the surgical complications. From the perspective of health economics, routine MRCP in patients with cholecystolithiasis before LC does not increase hospitalization costs, and is necessary and feasible.

Numerous studies related to esophagogastric junction cancer (EGC) have been published, and bibliometric analysis of these publications may be able to identify research hotspots and frontiers of EGC. Studies published on EGC between 2002 and 2021 were retrieved from the Web of Science Core Collection. The collaboration network of countries/regions, institutions, authors, co-citation network of journals, co-occurrence network, and overlay visualization of keywords were analyzed using the VOSviewer software. Cluster and timeline analyses of references were performed using the CiteSpace software. A total of 5109 English articles were published across 691 journals by authors affiliated with 4727 institutions from 81 countries/regions. The annual number of publications related to EGC research has exhibited an increasing trend. The United States, China, and Japan emerged as the top 3 prolific countries/regions. Institutions in the United States, Japan, and South Korea exhibited significant collaboration with one another. Diseases of the Esophagus was the most prolific journal, and Annals of Surgical Oncology, World Journal of Gastroenterology, and Gastric Cancer had also published more than 100 studies. Jaffer A Ajani was the most productive author while David Cunningham ranked the first in terms of total citations and average citations per article. Barrett’s esophagus, gastroesophageal reflux disease, Helicobacter pylori, and obesity were common topics in earlier research, and recent years had seen a shift towards the topics of immunotherapy, targeted therapy, and neoadjuvant chemotherapy. In conclusion, growing attention is paid to EGC research, especially in terms of immunotherapy, targeted therapy, and neoadjuvant chemotherapy.

Objective: Inflammation plays a pivotal role in the pathogenesis of stroke. However, the proteins that initiate inflammatory responses remain unclear. In this study, we utilize proteomics to identify the core protein in acute ischemic stroke (AIS) patients and verify the relationship of the protein with NOD-like receptor protein 3 (NLRP3). Methods: Peripheral blood from AIS patients and patients without AIS was collected and analyzed using a quantitative proteomic method (label-free) to screen for differential proteins. Subsequently, the differential protein was validated by ELISA. Additionally, a middle cerebral artery occlusion (MCAO) model was utilized to explore the relationship between mannose-binding lectin 2 (MBL2) and NLRP3. Co-immunoprecipitation (Co-IP) and western blot were also used to validate the interaction between the proteins and NLRP3. Results: A total often AIS patients and controls were enrolled in the proteomics study. Compared with the control group, a total of 49 proteins were identified as potential proteins. Among these proteins, MBL2 was notably increased in the AIS group and selected for further analysis. Subsequent ELISA analysis confirmed a significant elevation of MBL2 levels in stroke patients (P < 0.001). Further, in animal studies, Co-IP assays showed an interaction between MBL2 and NLRP3 proteins in cerebral tissue after ischemic infarction. Western blot results demonstrated that the expression levels of NLRP3 and MBL2 were significantly increased in MCAO rats. Conclusions: Our results suggest that MBL2 may be one of the promoters of inflammation by interacting with NLRP3 in AIS patients.

Background: Hyperuricemia is a serious health problem related to not only gout but also cardiovascular diseases (CVDs). Low-dose aspirin was reported to inhibit uric acid excretion, which leads to hyperuricemia. To decrease hyperuricemia-related CVD, this study aimed to identify the risk of hyperuricemia in people taking aspirin.Method: The original data of this cross-sectional study were obtained from the National Health and Nutrition Examination Survey between 2011 and 2018. Participants who filled in the “Preventive Aspirin Use” questionnaire with a positive answer were included in the analysis. Six machine learning algorithms were screened, and eXtreme Gradient Boosting (XGBoost) was employed to establish a model to predict the risk of hyperuricemia.Results: A total of 805 participants were enrolled in the final analysis, of which 190 participants had hyperuricemia. The participants were divided into a training set and testing set at a ratio of 8:2. The area under the curve for the training set was 0.864 and for the testing set was 0.811. The SHapley Additive exPlanations (SHAP) method was used to evaluate the performances of the modeling. Based on the SHAP results, the feature ranking interpretation showed that the estimated glomerular filtration rate, body mass index, and waist circumference were the three most important features for hyperuricemia in individuals taking aspirin. In addition, triglyceride, hypertension, total cholesterol, high-density lipoprotein, low-density lipoprotein, age, race, and smoking were also correlated with the development of hyperuricemia.Conclusion: A predictive model established by XGBoost algorithms can potentially help clinicians make an early detection of hyperuricemia risk in people taking low-dose aspirin.

ELMOD3 (encoding ELMO domain containing 3) is a causative gene associated with human autosomal dominant nonsyndromic and progressive hearing loss. However, the role of ELMOD3 in the occurrence and development of tumors remains unknown. Herein, we observed that inactivation of ELMOD3 in gastric cancer cells significantly inhibited their proliferation, migration, and invasion, and altered cell cycle progression. A xenograft tumor model showed that knockout of ELMOD3 suppressed the tumorigenicity of BGC823 gastric cancer cells in nude mice. Further investigation demonstrated that the ELMO domain of ELMOD3 interacts with beta-catenin, which increases the levels of beta-catenin, promoting downstream target gene expression. Deletion of ELMOD3 in gastric cells decreased the beta-catenin signaling, elevated E-cadherin levels, suppressed RAF/MEK/ERK signal pathway, and disrupted the formation of F-actin cytoskeleton. These results led us to propose that ELMOD3 may participate in multiple biological processes in promoting the tumorigenesis of gastric cancer. It exerts a positive role in the regulation of gastric cancer cell proliferation and progression. Thus, ELMOD3 was identified as a potential tumor target, which deserves further investigation.

目的 探讨三孔腹腔镜胃袖状切除术(three-port laparoscopic sleeve gastrectomy,TPLSG)和五孔腹腔镜胃袖状切除术(five-port laparoscopic sleeve gastrectomy,FPLSG)的安全性及有效性.方法 选取2019年7月至2020年7月首都医科大学附属北京世纪坛医院接受腹腔镜胃袖状切除术患者95例,根据手术trocar孔数不同分为TPLSG组(43例)和FPLSG组(52例).术后随访1 个月,比较两组患者的术后相关情况.结果 95例患者中,男42例,女53例,年龄19～64岁,平均(31.0±10.0)岁.按照1:1 匹配,每组各37例配对成功,匹配后两组的基线资料差异无统计学意义(P＞0.05).所有患者均顺利完成手术.两组患者手术时间、术中失血量、术后住院时间、住院费用、首次排气时间、开始流质饮食时间、额外体重丢失比例(excess weight loss％,EWL％)、术后并发症发生率及其缓解率的比较,差异均无统计学意义(P＞0.05);术后1个月随访,TPLSG组术后疼痛、美观及总体满意度高于FPLSG组,差异均有统计学意义(P＜0.05).结论 TPLSG和FPLSG同样安全、有效,其中TPLSG的切口更美观、患者疼痛更轻.

Background: Drug-induced cardiotoxicity (DICT) is one of the most serious adverse drug reactions, which is an important safety issue in drug development and clinical practice. This study aimed to summarize the knowledge structure and to detect emerging trends, and provide ideas for future research on DICT in children using bibliometric methods.Material/Methods: All publications on DICT in children were retrieved through the Web of Science Core Collection up to April 20, 2022. The document type was restricted to articles with the language set to English. CiteSpace and VOSviewer were used to conduct this bibliometric analysis.Results: A total of 298 articles were included, and the annual publications decreased since 2021. The United States was the leading country with the most publications (117), the highest centrality (0.39), and total citations (4055). The most influential institution was the University of British Columbia, while Carleton BC and Rassekh SR, both from Canada, were the most productive authors, but there was no leader in this field. The keywords with both high frequency and high centrality after excluding "cardiotoxicity" and "children" were acute lymphoblastic leukemia (Freq=43, Central=0.15), childhood cancer (Freq=42, Central=0.13), toxicity (Freq=33, Central=0.16), and breast cancer (Freq=29, Central=0.19). "Adriamycin cardiotoxicity" was the first burst keyword, while "childhood cancer", "oxidative stress", and "cardiac dysfunction" were emerging research hotspots.Conclusions: Attention to DICT in children was insufficient. This study serves as a breakthrough point, providing a comprehensive overview of the knowledge structure, development landscape, and future opportunities in this field.

There are increasing data on the potential risk of pancreatic carcinoma associated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). The study aimed to determine whether GLP-1RAs are associated with increased detection of pancreatic carcinoma based on the FDA Adverse Events Reporting System and clarify its potential mechanisms through keyword co-occurrence analysis from literature database. Disproportionality and Bayesian analyses were used for signal detection using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Mortality, life-threatening events, and hospitalizations were also investigated. VOSviewer was adopted to generate visual analysis of keyword hotspots. A total of 3073 pancreatic carcinoma cases were related to GLP-1RAs. Five GLP-1RAs were detected with signals for pancreatic carcinoma. Liraglutide had the strongest signal detection (ROR 54.45, 95

目的 调查住院患者人血白蛋白使用情况,并结合指南及循证证据对其临床使用情况进行分析,为后续开展白蛋白使用合理性评价提供参考,以促进临床合理用药.方法 随机抽取中国9个地区120家医院2016年1月—2020年12月住院患者使用人血白蛋白的数据,对人血白蛋白处方量、取药数量、消费金额、科室分布、适应证进行分析.结果 共抽取处方756 055张,人血白蛋白产品主要依赖进口.2016-2020年,人血白蛋白使用量呈稳态缓慢增加趋势.对9个地区平均每年每家医院处方量、取药数量及处方金额进行比较,排名前三位地区均为杭州、广州和成都,哈尔滨最低.人血白蛋白消耗巨大,平均每年每家医院消费金额207 695～2 213 604元.9个地区处方量和处方金额排名前3位的科室主要集中在重症监护室(ICU)和外科系统;肿瘤处方占比最多,其次为心脏和肝脏疾病.结论 人血白蛋白使用量巨大,部分适应证仍存在争议,需要进一步开展循证评价.有必要对人血白蛋白使用较多的科室和疾病领域开展专项点评,以降低不合理使用率,降低医疗成本,促进临床合理使用.

目的 探索住专一体化模式下普通外科手术分解分类带教的方法.方法 按照住院医师和专培医师培养要求,将普通外科常见手术及重大手术进行分类及分解,使不同层次的培训对象都能在手术中获得独立操作机会.结合Milestone,为住院医师和专培医师制定分阶段递进式的手术技术培养计划.对进入研究的住院医师和专培医师进行基线测试,并在出科时进行考核,与既往常规培养模式进行比较,探索该方案的有效性.结果 将普通外科常见手术及重大手术进行分解,分别由住院医师和专培医师进行独立操作,并由指导医师或上级医师完成手术的核心部分.以此为基础,为住院医师和专培医师制定分阶段递进式的手术技术培养计划,并制定手册.住专一体化模式下住院医师基线成绩为(33.08±3.85)分,既往常规培训模式基线成绩为(32.96±3.55)分,二者差异无统计学意义(P>0.05);住专一体化模式下住院医师出科成绩为(41.67±5.19)分,既往常规培训模式出科成绩为(39.14±5.67)分,二者差异具有统计学意义(P<0.05).住专一体化模式下专培医师基线成绩为(35.13±5.32)分,既往常规培训模式基线成绩为(34.93±6.04)分,二者差异无统计学意义(P>0.05);住专一体化模式下专培医师出科成绩为(45.27±5.20)分,既往常规培训模式出科成绩为(42.14±4.42)分,二者差异具有统计学意义(P<0.05).结论 与既往常规培养模式相比,住专一体化手术培养模式下的普通外科手术分解分类带教能够显著提高培训对象的手术操作能力.

BACKGROUND Long-term aspirin treatment was recommended for secondary prevention of cardiovascular and cerebrovascular disease. However, some studies reveal low-dose aspirin (LDA) can raise serum uric acid (SUA) levels. Thus, the purpose of this study was to analyze whether LDA intake is associated with hyperuricemia. MATERIAL AND METHODS Data was collected from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2018. All participants over 40 years old and who selected "preventive aspirin use" were included in the study. Logistic regression analyses were used to evaluate the relationship between LDA intake and hyperuricemia. The stratified analysis was based on race and estimated glomerular filtration rate (eGFR). RESULTS A total of 3540 participants were included in the study. Of them, 805 (22.7%) took LDA, and 190 (31.6%) had hyperuricemia. There was no significant association between hyperuricemia and LDA intake (OR=1.22, 95% CI: 0.97-1.54) after adjusting for confounding factors. However, further subgroup analysis by age showed a significant association between LDA intake and hyperuricemia (OR=3.44, 95% CI: 1.88-6.27) among those 40 to 50 years of age. After adjusting for confounding factors, the relationship was still significant (OR=2.28, 95% CI: 1.10-4.73); we also found that race (Hispanic American, OR=1.84, 95% CI: 1.11-3.06) and eGFR under 60 mL/min/1.73 m² (OR=1.94, 95% CI: 1.04-3.62) may play important roles in the development of hyperuricemia. CONCLUSIONS LDA does not increase the hyperuricemia risk in people over 40 years. However, those aged between 40 and 50 years, Hispanic American, and with impaired renal function should have careful evaluation during LDA treatment.