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Survival outcomes of population-wide colonoscopy screening: reanalysis of the NordICC data. 全民结肠镜筛查的生存结果:NordICC 数据的再分析。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-18 DOI: 10.1186/s12876-024-03506-2
Tomer Meirson, Gal Markel, Daniel A Goldstein

Background: Colonoscopy as a common screening practice to prevent colorectal cancer lacks strong evidence. NordICC, the first randomized trial of colonoscopy screening, reported no clear clinical benefit for colonoscopy in the intention-to-screen population with suggested benefit in the risk of colorectal incidence and cancer-specific mortality in the per-protocol analyses. However, although the study was designed to perform survival analysis, no survival outcomes were reported since the underlying assumption for hazard ratio was not valid. We aimed to assess whether colonoscopy screening is associated with improved survival outcomes compared with usual care.

Methods: We reconstructed patient-level data from the Kaplan-Meier estimator of the primary endpoints reported in NordICC for the intention-to-screen and adjusted per-protocol populations. The restricted-mean survival time difference (RMST-D) and restricted-mean time loss ratio (RMTL-R), which are robust alternatives to the hazard ratio without specific model assumptions, were calculated for colorectal cancer incidence and death.

Results: In this study, no significant difference in colorectal cancer incidence over 10 years was found in the intention-to-screen population (RMST-D: -0.68 days, 95% CI -3.9-2.6; RMTL-R: 1.04, 95% CI 0.88-1.22) or in the per-protocol analysis population (RMST-D: -2.9 days, 95% CI -6.5-0.67; RMTL-R: 1.15, 95% CI 0.97-1.35). In the intention-to-screen population, inviting individuals to colonoscopy did not improve colorectal-cancer death (RMST-D: -0.29 days, 95% CI -1.6-1.0; RMTL-R: 1.07, 95% CI 0.78-1.48). Over 10 years, in the per-protocol analysis, individuals who underwent colonoscopy survived an average of 1.1 more days free of colorectal cancer, but this difference was not statistically significant (RMST-D: 95% CI -0.13-2.3; RMTL-R: 0.72, 95% CI 0.49-1.07).

Conclusions: In this reanalysis of the NordICC data, no evidence of improvement in survival outcomes for participants invited to undergo colonoscopy compared to usual care was identified, even when assuming that all invited participants did undergo colonoscopy. Thus, our results do not support the use of colonoscopy as a population-wide screening test as a mean to decrease colorectal cancer incidence or death.

Registry: Not applicable.

背景:结肠镜检查作为预防结直肠癌的常用筛查方法缺乏有力证据。作为结肠镜筛查的首个随机试验,NordICC 报告称,在有意接受筛查的人群中,结肠镜检查没有明显的临床益处,但在按方案分析中,结肠直肠癌发病率和癌症特异性死亡率的风险显示出了益处。然而,尽管该研究旨在进行生存分析,但由于危险比的基本假设不成立,因此没有报告生存结果。我们的目的是评估与常规治疗相比,结肠镜筛查是否能改善生存结果:我们根据 NordICC 报告的主要终点的 Kaplan-Meier 估计器重建了意向筛查人群和调整后的按方案人群的患者水平数据。计算了结直肠癌发病率和死亡率的受限平均生存时间差(RMST-D)和受限平均时间损失比(RMTL-R),它们是危险比的稳健替代方法,无需特定的模型假设:在这项研究中,无论是意向筛查人群(RMST-D:-0.68 天,95% CI -3.9-2.6;RMTL-R:1.04,95% CI 0.88-1.22)还是按方案分析人群(RMST-D:-2.9 天,95% CI -6.5-0.67;RMTL-R:1.15,95% CI 0.97-1.35),10 年内结直肠癌发病率均无明显差异。在意向筛查人群中,邀请个人进行结肠镜检查并不会改善结直肠癌死亡(RMST-D:-0.29 天,95% CI -1.6-1.0; RMTL-R:1.07,95% CI 0.78-1.48)。在10年的按方案分析中,接受结肠镜检查的人平均多存活1.1天,未患结肠直肠癌,但这一差异无统计学意义(RMST-D:95% CI -0.13-2.3;RMTL-R:0.72,95% CI 0.49-1.07):在此次对NordICC数据的重新分析中,即使假定所有受邀者都接受了结肠镜检查,也没有发现与常规治疗相比,受邀者接受结肠镜检查后的生存结果有所改善的证据。因此,我们的结果并不支持将结肠镜检查作为一种全民筛查手段来降低结直肠癌的发病率或死亡率:不适用。
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引用次数: 0
The long-term impact of post-cholecystectomy major bile duct injury on liver stiffness. 胆囊切除术后主要胆管损伤对肝脏硬度的长期影响。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-18 DOI: 10.1186/s12876-024-03505-3
Avinash Jayasekara, Suchintha B Tillakaratne, Uditha Dasanayake, Shanthamoorthy Gishanthan, Rohan C Siriwardana

Introduction: Iatrogenic bile duct injuries (BDI) are a devastating complication. Long-term impact of corrective hepaticojejunostomy (HJ) for such injuries on post -surgery liver stiffness is lacking. Hence the aim of this study was to explore the extent of hepatic fibrosis in a cohort of patients with Strasberg E bile duct injuries who underwent HJ after a minimum follow-up of six months.

Methods: Out of 50 BDI presented over a period of 10-years, 19 patients with Strasberg type E, injuries that underwent HJ and completed a minimum 6-month follow-up [65.5 (7 -108)] period were selected. Data were prospectively collected on liver functions and liver stiffness was assessed using a Fibroscan. Their liver stiffness and degree of fibrosis was compared with (n = 38) age, gender and comorbidity matched controls.

Results: The median age was 47 (30-70) years, with 63% females. Primary HJ was performed in 84%, with a median time from injury to HJ of 7 (1-39) days. The total bilirubin was 16.5 (11.2) µmol/L, Alkaline Phosphatase was 102 (27.2) U/L, and Platelet count was 256 (77) x 103. Liver stiffness (median 6.4 kPa) did not significantly differ from controls (5.3 kPa). Fibrosis assessment revealed comparable distribution of F0 to F3 fibrosis between the study and control groups (F0/F1: 68.4% vs. 84.4%, F2: 10.5% vs. 9.4%). However, all three patients with right hepatic artery injury (p = 0.003) and three of five patients with bile duct stricture had F3/F4 fibrosis.

Conclusions: Major BDI repair demonstrates comparable liver fibrosis in the absence of artery injury and anastomotic strictures. Measuring liver fibrosis could be valuable in the presence of arterial injuries or anastomotic strictures.

导言:先天性胆管损伤(BDI)是一种破坏性并发症。针对此类损伤的肝空肠吻合术(HJ)对术后肝硬变的长期影响尚不明确。因此,本研究旨在探讨一组接受肝空肠吻合术的斯特拉斯堡E型胆管损伤患者在至少六个月的随访后肝纤维化的程度:方法: 从 50 名 10 年内就诊的 BDI 患者中,选择了 19 名接受 HJ 并完成至少 6 个月随访 [65.5 (7 -108)] 的斯特拉斯堡 E 型胆管损伤患者。前瞻性地收集了肝功能数据,并使用纤维扫描仪评估了肝脏硬度。他们的肝脏硬度和纤维化程度与年龄、性别和合并症相匹配的对照组(n = 38)进行了比较:中位年龄为 47(30-70)岁,女性占 63%。84%的患者进行了原发性 HJ,从受伤到 HJ 的中位时间为 7(1-39)天。总胆红素为 16.5 (11.2) µmol/L,碱性磷酸酶为 102 (27.2) U/L,血小板计数为 256 (77) x 103。肝硬度(中位数 6.4 kPa)与对照组(5.3 kPa)无明显差异。纤维化评估显示,研究组和对照组的 F0 至 F3 纤维化分布相当(F0/F1:68.4% 对 84.4%,F2:10.5% 对 9.4%)。然而,所有三位肝右动脉损伤患者(P = 0.003)和五位胆管狭窄患者中的三位都出现了F3/F4纤维化:结论:在没有动脉损伤和吻合口狭窄的情况下,BDI大修显示出相当的肝纤维化。在有动脉损伤或吻合口狭窄的情况下,测量肝纤维化可能很有价值。
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引用次数: 0
Advantages comparison of peritoneal drainage versus no drainage after laparoscopic appendectomy for complicated appendicitis: a meta-analysis. 腹腔镜阑尾切除术治疗复杂性阑尾炎后腹腔引流与不引流的优势比较:一项荟萃分析。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-16 DOI: 10.1186/s12876-024-03500-8
Hongsheng Wu, Biling Liao, Tiansheng Cao, Tengfei Ji, Yumei Luo, Jianbin Huang, Keqiang Ma

Background: Peritoneal drainage (PD) following laparoscopic appendectomy(LA) has long been considered beneficial for appendicitis patients, especially those with complicated appendicitis. However, recent research has raised doubts about the advantages of PD, as it not only fails to reduce postoperative complications but also prolongs the operative duration and hospital stay and incurs higher medical expenses. Given this controversy, we conducted a meta-analysis to determine whether drainage is necessary after LA for complicated appendicitis. This meta-analysis had registered in PROSPERO(ID: CRD42023472382).

Objective: This study assessed current evidence regarding the efficacy, safety, and potential benefits of drainage versus no drainage following LA for complicated appendicitis.

Methods: We conducted a comprehensive search of PubMed, Springer, and the Cochrane Library using the search terms "appendicitis", "laparoscopic appendectomy", and "drain" or "drainage" for studies published between January 1, 2000, and December 31, 2022. We employed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria for study inclusion and exclusion. Primary outcomes included postoperative intra-abdominal abscess, postoperative intestinal obstruction, postoperative stump leakage, wound infection and postoperative visual analog scale(VAS) score, while secondary outcomes consisted of operative time, postoperative recovery time and total hospitalization duration. Studies with at least two outcomes were considered for meta-synthesis. Depending on I2 values, fixed- or random effects models were used for data synthesis. Pooled odds ratios (OR) and weighted mean differences (WMD) were calculated for outcome comparisons between PD and no peritoneal drainage (NPD). Sensitivity analysis and meta-regression were performed to assess and investigate inter-study heterogeneity.

Results: After conducting our literature search and screening, twelve studies were analyzed, comprising 3374 cases. During the comparison of primary outcomes between PD and NPD, the incidence of wound infection and postoperative VAS score were significantly higher in the PD group(P < 0.05). While during the comparison of secondary outcomes, the operative duration, postoperative recovery time and hospitalization duration were significantly longer in the PD group than in the NPD group(P < 0.05).

Conclusion: PD following LA for complicated appendicitis not only increases the incidence wound infection and aggravate patients' postoperative pain, but also prolongs the operative duration, postoperative recovery time and hospitalization duration. Therefore, routine PD after LA for acute complicated appendicitis is not recommended.

背景:腹腔镜阑尾切除术(LA)后腹腔引流(PD)一直被认为对阑尾炎患者,尤其是复杂性阑尾炎患者有益。然而,最近的研究对腹腔引流术的优势提出了质疑,因为它不仅不能减少术后并发症,还会延长手术时间和住院时间,并产生更高的医疗费用。考虑到这一争议,我们进行了一项荟萃分析,以确定复杂性阑尾炎的 LA 术后是否需要引流。该荟萃分析已在 PROSPERO(ID:CRD42023472382)上注册:本研究评估了目前有关复杂性阑尾炎 LA 术后引流与不引流的疗效、安全性和潜在益处的证据:我们使用 "阑尾炎"、"腹腔镜阑尾切除术"、"引流 "或 "引流管 "等检索词对 PubMed、Springer 和 Cochrane 图书馆进行了全面检索,检索对象为 2000 年 1 月 1 日至 2022 年 12 月 31 日期间发表的研究。我们采用系统综述和荟萃分析首选报告项目(PRISMA)标准进行研究的纳入和排除。主要结果包括术后腹腔内脓肿、术后肠梗阻、术后残端渗漏、伤口感染和术后视觉模拟量表(VAS)评分,次要结果包括手术时间、术后恢复时间和总住院时间。荟萃综合考虑了至少有两项结果的研究。根据 I2 值的不同,采用固定效应或随机效应模型进行数据综合。针对腹腔引流术和无腹腔引流术(NPD)之间的结果比较,计算汇总的几率比(OR)和加权平均差(WMD)。进行了敏感性分析和元回归,以评估和调查研究间的异质性:经过文献检索和筛选,我们分析了 12 项研究,包括 3374 个病例。在比较PD和NPD的主要结果时,PD组的伤口感染发生率和术后VAS评分均显著高于NPD组(P 结论:PD组的伤口感染发生率和术后VAS评分均显著高于NPD组):复杂性阑尾炎 LA 术后行 PD 不仅会增加伤口感染的发生率,加重患者的术后疼痛,还会延长手术时间、术后恢复时间和住院时间。因此,不建议在急性复杂性阑尾炎 LA 术后常规进行腹腔镜手术。
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引用次数: 0
Impact of perioperative immunonutrition on postoperative outcomes in pancreaticoduodenectomy: a systematic review and meta-analysis of randomized controlled trials. 围手术期免疫营养对胰十二指肠切除术术后效果的影响:随机对照试验的系统回顾和荟萃分析。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-16 DOI: 10.1186/s12876-024-03510-6
Gaofeng Zhang, Bing Zhao, Tengang Deng, Xiaofei He, Yongpin Chen, Changtao Zhong, Jie Chen

Background: This systematic review and meta-analysis aimed to evaluate the impact of perioperative immunonutrition on postoperative outcomes in patients undergoing pancreaticoduodenectomy (PD).

Methods: Conducted a comprehensive search in PubMed, Embase, Cochrane Library, Medline, and Web of Science databases to identify all randomized controlled trials (RCTs) on the topic of immunonutrition and PD. Subsequently screened literature, extracted data, and assessed the risk of bias in the included studies, and finally conducted a meta-analysis using RevMan 5.3 software.

Results: The analysis included a total of 10 RCTs with 574 patients, among whom 288 were in the immunonutrition group and 283 in the control group. The meta-analysis revealed a significantly lower incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27-0.74; P = 0.002) and severe postoperative complications (OR = 0.61; 95% CI: 0.38-0.98; P = 0.04) in the immunonutrition group compared to the control group. Additionally, patients in the immunonutrition group had a significantly shorter length of hospital stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01). However, the analysis revealed no statistically significant difference in the overall complication rate between the two groups (P = 0.67). Furthermore, the incidence of specific complications and perioperative mortality rates also did not demonstrate any statistically significant differences (all P > 0.05).

Conclusions: Perioperative immunonutrition in PD patients can reduce postoperative infection-related complications, but more high-quality RCTs are needed for further validation.

背景:本系统综述和荟萃分析旨在评估围手术期免疫营养对胰十二指肠切除术(PD)患者术后效果的影响:本系统综述和荟萃分析旨在评估围手术期免疫营养对胰十二指肠切除术(PD)患者术后效果的影响:在PubMed、Embase、Cochrane Library、Medline和Web of Science数据库中进行全面检索,以确定所有以免疫营养和胰十二指肠切除术为主题的随机对照试验(RCT)。随后筛选文献、提取数据并评估纳入研究的偏倚风险,最后使用RevMan 5.3软件进行荟萃分析:分析共纳入了10项研究,574名患者,其中免疫营养组288人,对照组283人。荟萃分析显示,与对照组相比,免疫营养组术后感染相关并发症(OR = 0.45;95% CI:0.27-0.74;P = 0.002)和严重术后并发症(OR = 0.61;95% CI:0.38-0.98;P = 0.04)的发生率明显较低。此外,免疫营养组患者的住院时间明显缩短(MD=-1.87;95%CI -3.29-0.44;P = 0.01)。不过,分析结果显示,两组患者的总体并发症发生率没有明显的统计学差异(P = 0.67)。此外,特定并发症的发生率和围手术期死亡率也未显示出任何有统计学意义的差异(P均>0.05):结论:腹膜透析患者围手术期免疫营养可减少术后感染相关并发症,但还需要更多高质量的 RCT 进行进一步验证。
{"title":"Impact of perioperative immunonutrition on postoperative outcomes in pancreaticoduodenectomy: a systematic review and meta-analysis of randomized controlled trials.","authors":"Gaofeng Zhang, Bing Zhao, Tengang Deng, Xiaofei He, Yongpin Chen, Changtao Zhong, Jie Chen","doi":"10.1186/s12876-024-03510-6","DOIUrl":"10.1186/s12876-024-03510-6","url":null,"abstract":"<p><strong>Background: </strong>This systematic review and meta-analysis aimed to evaluate the impact of perioperative immunonutrition on postoperative outcomes in patients undergoing pancreaticoduodenectomy (PD).</p><p><strong>Methods: </strong>Conducted a comprehensive search in PubMed, Embase, Cochrane Library, Medline, and Web of Science databases to identify all randomized controlled trials (RCTs) on the topic of immunonutrition and PD. Subsequently screened literature, extracted data, and assessed the risk of bias in the included studies, and finally conducted a meta-analysis using RevMan 5.3 software.</p><p><strong>Results: </strong>The analysis included a total of 10 RCTs with 574 patients, among whom 288 were in the immunonutrition group and 283 in the control group. The meta-analysis revealed a significantly lower incidence of postoperative infection-related complications (OR = 0.45; 95% CI: 0.27-0.74; P = 0.002) and severe postoperative complications (OR = 0.61; 95% CI: 0.38-0.98; P = 0.04) in the immunonutrition group compared to the control group. Additionally, patients in the immunonutrition group had a significantly shorter length of hospital stay (MD= -1.87; 95%CI -3.29 - -0.44; P = 0.01). However, the analysis revealed no statistically significant difference in the overall complication rate between the two groups (P = 0.67). Furthermore, the incidence of specific complications and perioperative mortality rates also did not demonstrate any statistically significant differences (all P > 0.05).</p><p><strong>Conclusions: </strong>Perioperative immunonutrition in PD patients can reduce postoperative infection-related complications, but more high-quality RCTs are needed for further validation.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"412"},"PeriodicalIF":2.5,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11569618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma. 研究肝细胞癌中与脂肪酸代谢相关基因的诊断和预后意义。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-15 DOI: 10.1186/s12876-024-03495-2
Sha-Sha Zhao, Rong-Rong Bai, Bao-Hua Zhang, Xiao-Rui Sun, Nan Huang, Yan Chen, Zi-Jiu Sun, Li-Mei Sun, Yue Zhang, Zhong-Qi Cui
<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2-3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC.</p><p><strong>Methods: </strong>In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo.</p><p><strong>Results: </strong>Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967-0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033-6.605, P < 0.001; multivariate Cox regression analysis: HR = 2.801%, 95% CI = 1.553-5.049, P < 0.001). Additionally, in vitro and in vivo experiments demonstrated that SLC22A1 inhibits HCC tumor development, suggesting it may be a potential therapeutic target for HCC.</p><p><strong>Conclusions: </strong>These findings indicate a considerable value of specific FA metabolism-related genes in the diagnostic and prognostic evaluation of HCC, which provide novel insights into the disease's management, as well as has potential implications for personalized treatment strategies. However, further investigation of the effects of these model genes on HCC is re
背景:肝细胞癌(HCC)是全球发病率和致死率最高的癌症之一,死亡率每年约增加 2-3%。HCC 死亡率高、预后差的主要原因是早期诊断不准确,以及在无法进行肝移植时缺乏监测。脂肪酸(FA)代谢是一个关键的代谢途径,它为癌症(尤其是 HCC)提供能量和信号因子,并促进恶性肿瘤的发生。因此,探索与脂肪酸代谢相关的特异性诊断和预后特征是至关重要的,这样才能有效地早期诊断和监测 HCC:在这项研究中,我们利用与FA代谢通路相关的基因和加权基因共表达网络分析(WGCNA)建立了基因共表达网络,并确定了与HCC相关的枢纽基因(疾病WGCNA)和FA集群(集群WGCNA)。利用从基因表达总库数据库(GSE25097)下载的数据构建了诊断模型,并利用癌症基因组图谱队列建立了预后模型,其中应用了单变量 Cox 回归分析、多变量 Cox 风险模型和 LASSO Cox 回归分析。使用 CIBERSORT 评估了 HCC 细胞的免疫浸润。关键的 SLC22A1 基因的功能在体外和体内得到了实验验证:结果:12个重叠基因(CPEB3、ASPDH、DEPDC7、ETFDH、UGT2B7、GYS2、F11、ANXA10、CYP2C8、GLYATL1、C6和SLC22A1)从疾病和集群WGCNA中被鉴定为关键基因,并用于构建诊断和预后模型。RF模型的ROC曲线下面积(AUC)最高,为0.994,被认为是区分具有不同特征的HCC患者的最有效方法。从 RF 模型中选出前五个重要基因(C6、UGT2B7、SLC22A1、F11 和 CYP2C8)作为诊断基因进行进一步分析(ROC 曲线:AUC值=0.986,95%置信区间[95% CI] =0.967-0.999)。此外,还建立了由四个基因(GYS2、F11、ANXA10 和 SLC22A1)组成的风险评分公式,并进一步证明了其独立的预后能力(单变量 Cox 回归分析:危险比 [HR] = 3.664%,95% CI = 2.033-6.605,P 结论:这四个基因的风险评分公式均可用于进一步分析(ROC 曲线:AUC 值 = 0.986,95% 置信区间 [95 CI] = 0.967-0.999):这些研究结果表明,特定的 FA 代谢相关基因在 HCC 的诊断和预后评估中具有相当大的价值,为疾病的管理提供了新的见解,并对个性化治疗策略具有潜在的影响。然而,还需要进一步研究这些模型基因对 HCC 的影响。
{"title":"Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma.","authors":"Sha-Sha Zhao, Rong-Rong Bai, Bao-Hua Zhang, Xiao-Rui Sun, Nan Huang, Yan Chen, Zi-Jiu Sun, Li-Mei Sun, Yue Zhang, Zhong-Qi Cui","doi":"10.1186/s12876-024-03495-2","DOIUrl":"10.1186/s12876-024-03495-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2-3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967-0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033-6.605, P &lt; 0.001; multivariate Cox regression analysis: HR = 2.801%, 95% CI = 1.553-5.049, P &lt; 0.001). Additionally, in vitro and in vivo experiments demonstrated that SLC22A1 inhibits HCC tumor development, suggesting it may be a potential therapeutic target for HCC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings indicate a considerable value of specific FA metabolism-related genes in the diagnostic and prognostic evaluation of HCC, which provide novel insights into the disease's management, as well as has potential implications for personalized treatment strategies. However, further investigation of the effects of these model genes on HCC is re","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"409"},"PeriodicalIF":2.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy and safety of tanshinone IIA in combination with mesalazine in the treatment of ulcerative colitis: a Systematic review and meta-analysis. 丹参酮 IIA 联合美沙拉嗪治疗溃疡性结肠炎的疗效和安全性:系统回顾和荟萃分析。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-15 DOI: 10.1186/s12876-024-03496-1
Xiao Chen, Qiujun Zhou, Bolin Wang, Dandan Feng, Ronglin Jiang, Xi Wang

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC.

Methods: We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data.

Results: The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700).

Conclusion: This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

背景:溃疡性结肠炎(UC)是一种以结肠复发性炎症为特征的慢性炎症性肠病。丹参酮 IIA 是一种从传统中药中提取的化合物,具有抗炎特性,与美沙拉嗪联用可提高治疗效果。本研究旨在确定丹参酮 IIA 联合美沙拉嗪治疗 UC 的总体反应率:我们在 PubMed、Embase、Cochrane Library、CNKI、万方、CQVIP 和 CBM 数据库中查阅了从数据库建立到 2023 年 4 月的文章。其中包括一项随机对照试验,干预组服用丹参酮 IIA 加美沙拉秦(T + M),而对比组仅服用美沙拉秦(M)。我们删除了重复或相似的论文;没有全文或数据不完整的论文;动物研究;综述和系统综述文章。我们使用 STATA 15.1 对数据进行了分析:结果发现,T + M 的总有效率高于 M,且差异显著(P = 0.000)。此外,汇总结果显示,T+M 组的 TNF-α (P = 0.000) 和 CRP (P = 0.000) 水平均显著低于 M 组。此外,与 M 组相比,T+M 组的 MHC-II 表达较少(P = 0.001)。然而,T + M 组和 M 组的不良反应发生率没有明显差异(P = 0.700):这项荟萃分析表明,与单独使用美沙拉嗪相比,丹参酮 IIA 与美沙拉嗪联合使用可显著提高溃疡性结肠炎的总体疗效。丹参酮 IIA 还具有抗炎作用,可降低 TNF-α、CRP 水平和 MHC-II 表达,且不会明显增加不良反应。尽管存在一些局限性,但这些研究结果表明,丹参酮 IIA 可以作为一种很有前景的溃疡性结肠炎辅助疗法。还需要进一步开展大规模、多中心研究,以证实这些结果,并确定这种联合疗法的长期安全性和有效性。
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引用次数: 0
Risk factors and prognostic impact of new decompensated events in hospitalized patients with decompensated cirrhosis. 肝硬化失代偿期住院患者发生新的失代偿事件的风险因素和预后影响。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-14 DOI: 10.1186/s12876-024-03494-3
Yan Lan, Yue Yu, Xiuding Zhang, Xianbin Xu, Xia Yu, Huilan Tu, Shaoheng Ye, Haoda Weng, Yu Shi, Jifang Sheng

Background: Decompensated cirrhosis (DC) is prone to recurrent episodes of decompensation following the initial event. This study aimed to identify the risk factors for subsequent decompensation and assess their impact on the outcomes of patients hospitalized for DC.

Methods: Patients with DC were divided into two groups based on the occurrence of new decompensated events during hospitalization. Logistic regression analysis was employed to identify risk factors for new decompensation. The Cox proportional hazards model was used to evaluate the relationship between new decompensation and short-term mortality risk in these patients.

Results: The study cohort consisted of 339 patients with DC, with a median age of 57 years. During hospitalization, 83 patients (24.5%) experienced new decompensated events, with bacterial infections (BIs) being the most common (n = 46, 13.6%). Multivariate analysis revealed that the Model for End-Stage Liver Disease (MELD) score at admission (OR = 1.06, 95% CI: 1.02-1.11, P = 0.005) was the sole risk factor for new decompensation during hospitalization. Patients who experienced new decompensation had significantly higher 28-day (28.9% vs. 7.0%, P < 0.001) and 90-day (33.7% vs. 15.2%, P < 0.001) transplant-free mortality compared to those who did not. After adjusting for white cell count, C-reactive protein, and MELD score, new decompensation during hospitalization was identified as an independent risk factor for 28-day and 90-day mortality (HR = 2.63, 95% CI: 1.42-4.87, P = 0.002 and HR = 1.73, 95% CI: 1.04-2.88, P = 0.033, respectively).

Conclusions: Patients with high MELD scores are susceptible to new decompensation during hospitalization, and the occurrence of new decompensation adversely affects short-term mortality in patients with DC.

背景:失代偿性肝硬化(DC)在初次失代偿后容易反复发作。本研究旨在确定后续失代偿的风险因素,并评估其对肝硬化住院患者预后的影响:方法:根据住院期间新发生的失代偿事件将直流电患者分为两组。采用逻辑回归分析确定新的失代偿风险因素。采用 Cox 比例危险模型评估这些患者新的失代偿与短期死亡风险之间的关系:研究队列由 339 名 DC 患者组成,中位年龄为 57 岁。住院期间,83 名患者(24.5%)发生了新的失代偿事件,其中细菌感染(BIs)最为常见(n = 46,13.6%)。多变量分析显示,入院时的终末期肝病模型(MELD)评分(OR = 1.06,95% CI:1.02-1.11,P = 0.005)是住院期间出现新的失代偿的唯一风险因素。出现新的失代偿的患者在 28 天内的失代偿率明显更高(28.9% vs. 7.0%,P 结论:MELD 评分高的患者在 28 天内的失代偿率明显更高:MELD 评分高的患者在住院期间容易出现新的失代偿,而新的失代偿的发生会对 DC 患者的短期死亡率产生不利影响。
{"title":"Risk factors and prognostic impact of new decompensated events in hospitalized patients with decompensated cirrhosis.","authors":"Yan Lan, Yue Yu, Xiuding Zhang, Xianbin Xu, Xia Yu, Huilan Tu, Shaoheng Ye, Haoda Weng, Yu Shi, Jifang Sheng","doi":"10.1186/s12876-024-03494-3","DOIUrl":"10.1186/s12876-024-03494-3","url":null,"abstract":"<p><strong>Background: </strong>Decompensated cirrhosis (DC) is prone to recurrent episodes of decompensation following the initial event. This study aimed to identify the risk factors for subsequent decompensation and assess their impact on the outcomes of patients hospitalized for DC.</p><p><strong>Methods: </strong>Patients with DC were divided into two groups based on the occurrence of new decompensated events during hospitalization. Logistic regression analysis was employed to identify risk factors for new decompensation. The Cox proportional hazards model was used to evaluate the relationship between new decompensation and short-term mortality risk in these patients.</p><p><strong>Results: </strong>The study cohort consisted of 339 patients with DC, with a median age of 57 years. During hospitalization, 83 patients (24.5%) experienced new decompensated events, with bacterial infections (BIs) being the most common (n = 46, 13.6%). Multivariate analysis revealed that the Model for End-Stage Liver Disease (MELD) score at admission (OR = 1.06, 95% CI: 1.02-1.11, P = 0.005) was the sole risk factor for new decompensation during hospitalization. Patients who experienced new decompensation had significantly higher 28-day (28.9% vs. 7.0%, P < 0.001) and 90-day (33.7% vs. 15.2%, P < 0.001) transplant-free mortality compared to those who did not. After adjusting for white cell count, C-reactive protein, and MELD score, new decompensation during hospitalization was identified as an independent risk factor for 28-day and 90-day mortality (HR = 2.63, 95% CI: 1.42-4.87, P = 0.002 and HR = 1.73, 95% CI: 1.04-2.88, P = 0.033, respectively).</p><p><strong>Conclusions: </strong>Patients with high MELD scores are susceptible to new decompensation during hospitalization, and the occurrence of new decompensation adversely affects short-term mortality in patients with DC.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"408"},"PeriodicalIF":2.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients. 经皮胃起搏治疗对早期急性胰腺炎患者胃肠道蠕动恢复和炎症改善的机制研究
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-13 DOI: 10.1186/s12876-024-03498-z
Zhenyu Jia, Lingchao Kong, Xiaochun Lu, Jianying Lu, Yuying Shen, Zhenguo Qiao, Tingting Xia

Purpose: Acute pancreatitis (AP) is often accompanied by gastrointestinal motility disorders. The purpose of this study was to investigate the efficacy and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients.

Materials and methods: Sixty-five AP patients were randomly divided into conventional treatment group and TGP group. The serum ghrelin and vasoactive intestinal peptide (VIP) were used to assess the possible gastrointestinal hormonal mechanism involved. The parameters of electrogastrogram (EGG) were used to evaluate the gastric motility in AP patients. The first defecation time was used to assess the recovery of intestinal motility. The heart rate variability (HRV) test was performed to assess autonomic nervous function.

Results: Compared with the conventional treatment group, the TGP treatment significantly improved symptoms in early AP patients, and shortened the first defecation time (p < 0.05) and the hospital days (p < 0.05). The level of VIP (P < 0.05) was also decreased in TGP group. The percentage of normal gastric slow waves (GSWS) (p < 0.05) was increased. The interleukin (IL)-6 level was decreased (P < 0.05). Concurrently, the vagal activity (HF) was increased (p < 0.01), the sympathetic activity (LF) was decreased (p < 0.01), and the ratio of sympathetic vagal (LF/HF) was decreased (p < 0.01).

Conclusions: The TGP treatment significantly improves the clinical symptoms in early AP patients. It also increases the percentage of normal GSWS. The therapeutic effect of TGP may be caused by autonomic nervous function mechanisms.

目的:急性胰腺炎(AP)通常伴有胃肠道运动障碍。本研究旨在探讨经皮胃起搏(TGP)对早期急性胰腺炎患者的疗效和可能的机制:65 例 AP 患者被随机分为常规治疗组和 TGP 组。采用血清胃泌素和血管活性肠肽(VIP)评估可能的胃肠激素机制。胃电图(EGG)参数用于评估 AP 患者的胃运动情况。首次排便时间用于评估肠蠕动的恢复情况。心率变异性(HRV)测试用于评估自律神经功能:结果:与常规治疗组相比,TGP 治疗明显改善了早期 AP 患者的症状,并缩短了首次排便时间(PTGP治疗能明显改善早期AP患者的临床症状。它还能提高正常 GSWS 的比例。TGP 的治疗效果可能是由自主神经功能机制引起的。
{"title":"The mechanism of transcutaneous gastric pacing treatment on gastrointestinal motility recovery and inflammation improvement in early-stage acute pancreatitis patients.","authors":"Zhenyu Jia, Lingchao Kong, Xiaochun Lu, Jianying Lu, Yuying Shen, Zhenguo Qiao, Tingting Xia","doi":"10.1186/s12876-024-03498-z","DOIUrl":"10.1186/s12876-024-03498-z","url":null,"abstract":"<p><strong>Purpose: </strong>Acute pancreatitis (AP) is often accompanied by gastrointestinal motility disorders. The purpose of this study was to investigate the efficacy and possible mechanism of transcutaneous gastric pacing (TGP) in early-stage AP patients.</p><p><strong>Materials and methods: </strong>Sixty-five AP patients were randomly divided into conventional treatment group and TGP group. The serum ghrelin and vasoactive intestinal peptide (VIP) were used to assess the possible gastrointestinal hormonal mechanism involved. The parameters of electrogastrogram (EGG) were used to evaluate the gastric motility in AP patients. The first defecation time was used to assess the recovery of intestinal motility. The heart rate variability (HRV) test was performed to assess autonomic nervous function.</p><p><strong>Results: </strong>Compared with the conventional treatment group, the TGP treatment significantly improved symptoms in early AP patients, and shortened the first defecation time (p < 0.05) and the hospital days (p < 0.05). The level of VIP (P < 0.05) was also decreased in TGP group. The percentage of normal gastric slow waves (GSWS) (p < 0.05) was increased. The interleukin (IL)-6 level was decreased (P < 0.05). Concurrently, the vagal activity (HF) was increased (p < 0.01), the sympathetic activity (LF) was decreased (p < 0.01), and the ratio of sympathetic vagal (LF/HF) was decreased (p < 0.01).</p><p><strong>Conclusions: </strong>The TGP treatment significantly improves the clinical symptoms in early AP patients. It also increases the percentage of normal GSWS. The therapeutic effect of TGP may be caused by autonomic nervous function mechanisms.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"407"},"PeriodicalIF":2.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The efficacy of CT-P13, a biosimilar of infliximab, in inflammatory bowel diseases: a systematic review and meta-analysis. 英夫利昔单抗的生物仿制药 CT-P13 对炎症性肠病的疗效:系统综述和荟萃分析。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-12 DOI: 10.1186/s12876-024-03480-9
Xinyue Hu, Xiaowei Tang, Limin Li, Lian Luo, Xinsen He, Qin Yan, Xiaolin Zhong

Background: Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation.

Methods: Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included.

Results: The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08-14 weeks were 0.66 (95% CI, 0.58-0.75) and 0.48 (95% CI, 0.43-0.54), respectively, and at 100-104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24-32 weeks were 0.84 (95% CI, 0.77-0.92) and 0.78 (95% CI, 0.63-0.93), respectively, and at 48-54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08-14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48-54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis.

Conclusions: CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.

背景:自 2015 年以来,英夫利昔单抗生物类似物 CT-P13 已在许多国家获准商业使用,减轻了社会和患者的经济负担。许多研究 CT-P13 治疗 IBD 的临床试验已经开展,并报道 CT-P13 可替代英夫利西单抗。然而,CT-P13与英夫利昔单抗原研药在疗效上的差异需要进一步阐明:方法:使用 Stata MP 17 对 IBD 的临床反应率、临床缓解率和粘膜愈合率数据进行汇总,并进行随机效应模型荟萃分析。共纳入 30 项研究:克罗恩病和溃疡性结肠炎患者初次使用生物制剂的临床缓解率在08-14周的集合风险分别为0.66(95% CI,0.58-0.75)和0.48(95% CI,0.43-0.54),在100-104周的集合风险分别为0.66(95% CI,0.49-0.84)和0.71(95% CI,0.62-0.79)。克罗恩病和溃疡性结肠炎患者在24-32周时从原用药过渡的临床缓解率汇总风险分别为0.84(95% CI,0.77-0.92)和0.78(95% CI,0.63-0.93),在48-54周时分别为0.72(95% CI,0.62-0.82)和0.78(95% CI,0.71-0.86)。溃疡性结肠炎患者的粘膜愈合率汇总结果为:08-14 周为 0.56(95% CI:0.46-0.67),48-54 周为 0.64(95% CI:0.42-0.85)。RCT研究显示,无论是克罗恩病还是溃疡性结肠炎,换药后疗效均无明显变化:结论:CT-P13在短期和长期内均有效。结论:CT-P13在短期和长期内均有效,应用CT-P13治疗IBD前景广阔。
{"title":"The efficacy of CT-P13, a biosimilar of infliximab, in inflammatory bowel diseases: a systematic review and meta-analysis.","authors":"Xinyue Hu, Xiaowei Tang, Limin Li, Lian Luo, Xinsen He, Qin Yan, Xiaolin Zhong","doi":"10.1186/s12876-024-03480-9","DOIUrl":"10.1186/s12876-024-03480-9","url":null,"abstract":"<p><strong>Background: </strong>Since 2015, an infliximab biosimilar, CT-P13, has been approved for commercial use in many countries, easing the economic burden borne by society and patients. Many clinical trials investigating CT-P13 for the treatment of IBD have been conducted and reported that it may be a substitute for infliximab. However, the differences between the efficacy of CT-P13 and infliximab-originator require further elucidation.</p><p><strong>Methods: </strong>Data on the rates of clinical response, clinical remission, and mucosal healing of IBD were pooled for random-effects model meta-analysis using Stata MP 17. A total of 30 studies were included.</p><p><strong>Results: </strong>The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were naïve to biologics at 08-14 weeks were 0.66 (95% CI, 0.58-0.75) and 0.48 (95% CI, 0.43-0.54), respectively, and at 100-104 weeks were 0.66 (95% CI, 0.49 to 0.84) and 0.71 (95% CI, 0.62 to 0.79) respectively. The pooled risk of clinical remission rate of patients with Crohn's disease and ulcerative colitis who were transitioned from the original agent at 24-32 weeks were 0.84 (95% CI, 0.77-0.92) and 0.78 (95% CI, 0.63-0.93), respectively, and at 48-54 weeks were 0.72 (95% CI, 0.62 to 0.82) and 0.78 (95% CI, 0.71 to 0.86) respectively. The pooled rates for mucosal healing in ulcerative colitis were 0.56 (95% CI: 0.46 to 0.67) at 08-14 weeks, and 0.64 (95% CI: 0.42 to 0.85) at 48-54 weeks. RCT studies showed no significant change in efficacy after switching, whether Crohn's disease or ulcerative colitis.</p><p><strong>Conclusions: </strong>CT-P13 is effective in short and long-term periods. The application of CT-P13 for the management of IBD was promising.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"406"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis. 7-羟基香豆素通过抑制 MAPK 通路和缓解肠道微生物群失调,改善小鼠溃疡性结肠炎。
IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Pub Date : 2024-11-12 DOI: 10.1186/s12876-024-03499-y
Mengqi Liu, Huayi Sun, Hao Fu, Lingping Fu, Xiao Zheng, Yu Chen

Objective: This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation.

Methods: To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments.

Results: Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome.

Conclusion: 7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.

研究目的本研究旨在通过网络药理学和实验验证,阐明7-羟基香豆素(7-HC)对溃疡性结肠炎(UC)的药理机制:为了研究7-羟基香豆素对溃疡性结肠炎的治疗作用,我们在小鼠的饮用水中添加了3.0%的右旋糖酐硫酸钠(DSS),建立了溃疡性结肠炎小鼠模型。随后,我们利用网络药理学方法预测了7-HC治疗UC的核心靶点和信号通路。最后,通过分子对接、分子动力学模拟和体内实验进一步验证了网络药理学的见解:结果:给 UC 小鼠口服 7-HC 可明显改善结肠炎指标。此外,7-HC 还能明显降低结肠中炎症细胞因子(TNF-α、IL-1β)的水平,并调节氧化应激指标(MPO、SOD)。随后的研究发现,7-HC 可抑制 UC 小鼠结肠中的两个核心靶点(AKT1 和表皮生长因子受体)。网络药理学和实验验证表明,7-HC 可以减少 MAPK 通路标志物 P38、JNK、ERK 的表达及其磷酸化;7-HC 还可以通过调节肠道微生物组来改善 UC。这是首次发现 7-HC 可通过抑制 MAPK 通路和调节肠道微生物群来治疗 UC,为 7-HC 治疗 UC 的药理机制提供了一个全新的视角。
{"title":"7-hydroxycoumarin ameliorates ulcerative colitis in mice by inhibiting the MAPK pathway and alleviating gut microbiota dysbiosis.","authors":"Mengqi Liu, Huayi Sun, Hao Fu, Lingping Fu, Xiao Zheng, Yu Chen","doi":"10.1186/s12876-024-03499-y","DOIUrl":"10.1186/s12876-024-03499-y","url":null,"abstract":"<p><strong>Objective: </strong>This research aimed to delineate the pharmacological mechanisms of 7-Hydroxycoumarin (7-HC) on ulcerative colitis (UC) employing network pharmacology and experimental validation.</p><p><strong>Methods: </strong>To investigate the therapeutic effects of 7-HC on UC, a UC mouse model was established through the unrestricted intake of 3.0% dextran sulfate sodium (DSS) in their drinking water. Subsequently, we predicted the core targets and signaling pathways of 7-HC for the treatment of UC using the network pharmacology approach. Finally, the insights gained from network pharmacology were further validated by molecular docking, molecular dynamics simulation as well as in vivo experiments.</p><p><strong>Results: </strong>Administering 7-HC orally to mice with UC led to a marked improvement in colitis indicators. Furthermore, 7-HC significantly lowered the levels of inflammatory cytokines (TNF-α, IL-1β) in the colon and modulated oxidative stress markers (MPO, SOD). Subsequent studies identified 2 core targets (AKT1 and EGFR) in the colon of UC mice that were inhibited by 7-HC. Network pharmacology and experimental validation showed that 7-HC can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation; 7-HC can also ameliorate UC by regulating the gut microbiome.</p><p><strong>Conclusion: </strong>7-HC demonstrates considerable efficacy in alleviating UC in mice, primarily through substantial diminution of tissue inflammation and oxidative stress. This is the first time that 7-HC has been found to treat UC by inhibiting the MAPK pathway and modulating the gut microbiota, providing a fresh perspective on the pharmacological mechanisms through which 7-HC operates in the management of UC.</p>","PeriodicalId":9129,"journal":{"name":"BMC Gastroenterology","volume":"24 1","pages":"405"},"PeriodicalIF":2.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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