BACKGROUND AND AIMS:Circumferential endoscopic submucosal dissection (C-ESD) is increasingly used for circumferential superficial esophageal squamous cell carcinoma (C-ESCC), although outcome data remain sparse. This study aimed to evaluate the short- and long-term outcomes of C-ESD in patients with C-ESCC. METHODS:Clinical outcomes of patients with C-ESCC undergoing C-ESD at 2 Chinese centers were analyzed. Short-term outcomes included en bloc resection rate, curative resection rate, operation time, and adverse events. Long-term outcomes comprised overall survival (OS), disease-specific survival (DSS), cumulative recurrence rate (CRR), and the efficacy of stricture prevention and management. RESULTS:A final assessment was conducted in 100 patients (100 lesions). The median lesion length was 5.2 cm (IQR, 4.5-6.0). Technical success rates were as follows: en bloc resection, 92.0% (95% CI, 85.0-96.4); R0 resection, 84.0% (95% CI, 75.6-90.5); and curative resection, 81.0% (95% CI, 72.3-88.3). The median procedure duration was 97.5 minutes (IQR, 70.5-138.3). Adverse events included delayed bleeding (3.0%), perforation (1.0%), and strictures (88.0%). With a median follow-up of 47.4 months (IQR, 34.3-65.2), 3- and 5-year OS and DSS were identical at 95.6% (95% CI, 91.4-99.9). Cumulative recurrence increased from 16.2% (3 years) to 19.8% (5 years). Prophylactic measures reduced stricture incidence (80% vs 100%; P = .007) and median number of endoscopic dilation sessions, 3 (IQR, 1-6) vs 4 (IQR, 3-9.8); P = .028. Stricture resolution was achieved in 95.5% of cases. CONCLUSIONS:C-ESD is an effective treatment for C-ESCCs. Although it achieves reliable oncological control with a favorable prognosis, its value is tempered by high stricture rates and a nonnegligible recurrence risk (∼20%). To optimize patient outcomes, advancing stricture prevention and ensuring rigorous long-term management are crucial future directions.
Since the sensitivity and accuracy of traditional detection for early gastric cancer diagnosis are still insufficient, it is significant to continuously optimize the optical molecular imaging detection technology based on an endoscopic platform. The signal intensity and stability of traditional chemical fluorescent dyes are low, which hinders the clinical application of molecular imaging detection technology. This work developed a probe based on perovskite quantum dots (PQDs) and peptide ligands. By utilizing CsPbBr3perovskite PQDs modified by azithromycin (AZI), combined with the specific polypeptide ligand of CD44v6, a gastric cancer biomarker, the perovskite-based probe (AZI-PQDs probe) which can specifically identify gastric cancer tumor was prepared. Owing to the high photoluminescence quantum yield of CsPbBr3PQDs, the naked eye can observe the imaging under the excitation of the hand-held ultraviolet light source. AZI-PQDs probe can accurately identify gastric cancer cells, tissues, and xenograft models with experiments ofex vivoandin vivofluorescence imaging detection. It also exhibited low toxicity and immunogenicity, indicating the safety of the probe. This work provides a probe combined with cancer specificity and a reliable fluorescent signal that has the potential for application in gastric cancer optical molecular imaging.
Esophageal cancer (EC) is a common and deadly malignancy of the digestive system. Currently, effective treatments for EC are limited and patient prognosis remains poor. In this study, we utilized Mendelian Randomization (MR) to identify potential drug targets for EC by analyzing proteins linked to the disease risk. A total of 734 plasma proteins and 4,479 druggable genes were obtained from recent studies, and two-sample MR analyses were conducted to investigate causal relationships between these proteins and EC. The cis-pQTL data of the proteins was analyzed after filtering. The inverse variance weighted (IVW) method was the primary analytical approach in MR analysis. Steiger filtering, heterogeneity and pleiotropy tests, Summary-data-based Mendelian Randomization (SMR) analysis, and Bayesian co-localization analysis were implemented to consolidate the results further. Moreover, drugs corresponding to the identified proteins were found in the DrugBank database. Five proteins HPSE, ST3GAL1, CEL, KLK13, and GNRH2 were identified as highly associated with EC. HPSE and GNRH2 showed protective effects with odds ratios (OR) of 0.80 (95% confidence interval [CI], 0.70-0.92) and 0.73 (95% CI 0.54-0.98), respectively. In contrast, increased expression of ST3GAL1(OR, 1.37; 95% CI 1.04-1.82), CEL (OR, 1.27; 95% CI 1.08-1.49), and KLK13 (OR, 1.22; 95% CI 1.04-1.42) were all associated with a higher risk of EC. In addition, the HPSE protein showed moderate colocalization with EC [coloc.abf-posterior probability of hypothesis 4 (PPH4) = 0.637]. Furthermore, the sensitivity analyses indicated no heterogeneity or pleiotropy. Therefore, these findings present promising drug targets for EC and deserve further clinical investigation.
Identify risk factors for esophageal stricture persisting despite standard oral steroid prophylaxis after endoscopic submucosal dissection (ESD) for large-area superficial esophageal cancer.Methods: Retrospective analysis of 202 patients undergoing ESD (≥ 2/3 circumferential resection) with postoperative oral steroids. Patients were stratified by stricture occurrence. Univariate and multivariate logistic regression evaluated lesion/ESD-related risk factors. Refractory stricture (RS; requiring ≥ 5 endoscopic dilations) and non-refractory stricture (NRS) groups were compared for endoscopic balloon/bougie dilation (EBD) continuation rates.Results: The overall stricture rate was 35.2% (71/202). Multivariate analysis identified four independent risk factors: longitudinal diameter ≥ 5 cm (OR 3.06, 95%CI 1.38–6.80), circumferential involvement > 4/5 (OR 6.41, 95%CI 2.79–14.67), entire circumferential involvement (OR 54.91, 95%CI 11.02-273.68), and muscular injury (OR 21.89, 95%CI 4.04-118.58). EBD continuing rates at 1 year were 70% (RS) vs.22.9% (NRS); at 3 years, rates decreased to 20% (RS) and 2.1% (NRS). RS showed significantly higher EBD continuation (Chi-square 8.404, P = 0.004).Conclusion: In patients with large superficial esophageal cancers involving ≥ 2/3 circumference who receive oral steroid prophylaxis, circumferential involvement ≥ 4/5 or entire circumferential involvement, longitudinal lesions ≥ 5 cm, and muscular injury independently predict steroid-resistant strictures post-ESD. High-risk patients require cautious ESD planning and novel stricture prevention strategies. RS necessitates prolonged EBD management, reflecting poorer therapeutic response.
BACKGROUND:Ectopic pregnancy (EP) is a dangerous obstetric condition that can occur anywhere throughout the world. This study explored the burden, health inequality analysis, and future trends related to EP to assist in formulating the next steps of public health policies. METHODS:The epidemiological characteristics of EP classified by age, year, and socioeconomic level were assessed in global, regional, and national groups based on Global Burden of Disease 2019. This study analyzed incidence, mortality, disability-adjusted life years (DALYs), age-standardized rate (ASR); average annual percentage change (AAPC), andestimated annual percentage change (EAPC).The article further predicts its change over the next 30 years and quantifies cross-national health inequalities. RESULTS:In 2019, the global number of new cases was 6,692,404.75 (95 % UI = 5,225,400.95-8,598,569.75), a decrease from 7,453,267.43 (95 % UI = 5,738,984.72-9,557,077.85) in 1990; and the age-standardized deaths rate (ASDR) was 0.16 (95 % UI = 0.14-0.19), a slight decrease from 0.22 (95 % UI = 0.19-0.24) in 1990.The EAPC for ASDR showed an average annual decrease of -0.91 (95 % CI = -1.04 - -0.78). In addition, ASR DALYs of EP decreased from 12.46 (95 % UI = 11.09-13.91) in 1990 to 9.69 (95 % UI = 8.27-11.31) in 2019. Projections indicate that by 2049, the ASIR will rise to 149.91 (95 % UI = 11.77-288.05) and the ASDR will rise to 0.18 (95 % UI = 0.05-0.31). Concentration indices of EP death and DALYs increased between 1990 and 2019. Health inequalities show that the concentration index for the EP DALY ratio decreased from -0.46 (95 % CI = -0.55 to -0.38) in 1990 to -0.61 (95 % CI = -0.70 to -0.52) in 2019 and the concentration index for EP death decreased from -0.47 (95 %CI = -0.56 to -0.39) in 1990 to -0.62 (95 %CI = -0.71- -0.53) in 2019. CONCLUSIONS:This study emphasizes the significant burden of EP, especially for low socio-demographic index countries. Addressing health inequality is crucial for developing effective intervention policies to improve global maternal health outcomes.
Gastroesophageal reflux disease (GERD) is associated with sleep disturbances. However, mechanisms underlying these interactions remain unclear. Male acute and chronic sleep deprivation (SD) mice were used for this study. Mice in the chronic SD group exhibited anxiety- and depression-like behaviors. We further performed high-throughput genome sequencing and bioinformatics analysis to screen for featured differentially expressed genes (DEGs) in the esophageal tissue. The acute SD group, comprised 25 DEGs including 14 downregulated and 11 upregulated genes. Compared with the acute SD group, more DEGs were present in the chronic SD group, with a total of 169 DEGs, including 88 downregulated and 81 upregulated genes. Some DEGs that were closely related to GERD and associated esophageal diseases were significantly different in the chronic SD group. Quantitative real-time polymerase chain reaction verified the downregulation of Krt4, Krt13, Krt15 and Calml3 and upregulation of Baxl1 and Per3. Notably, these DEGs are involved in biological processes, which might be the pathways of the neuroregulatory mechanisms of DEGs expression.
BackgroundPrevious epidemiological studies have found a link between colorectal cancer (CRC) and human dietary habits. However, the inherent limitations and inevitable confounding factors of the observational studies may lead to the inaccurate and doubtful results. The causality of dietary factors to CRC remains elusive.MethodsWe conducted two-sample Mendelian randomization (MR) analyses utilizing the data sets from the IEU Open GWAS project. The exposure datasets included alcoholic drinks per week, processed meat intake, beef intake, poultry intake, oily fish intake, non-oily fish intake, lamb/mutton intake, pork intake, cheese intake, bread intake, tea intake, coffee intake, cooked vegetable intake, cereal intake, fresh fruit intake, salad/raw vegetable intake, and dried fruit intake. In our MR analyses, the inverse variance weighted (IVW) method was employed as the primary analytical approach. The weighted median, MR-Egger, weighted mode, and simple mode were also applied to quality control. Heterogeneity and pleiotropic analyses were implemented to replenish the accuracy of the results.ResultsMR consequences revealed that alcoholic drinks per week [odds ratio (OR): 1.565, 95% confidence interval (CI): 1.068–2.293, p = 0.022], non-oily fish intake (OR: 0.286; 95% CI: 0.095–0.860; p = 0.026), fresh fruit intake (OR: 0.513; 95% CI: 0.273–0.964; p = 0.038), cereal intake (OR: 0.435; 95% CI: 0.253–0.476; p = 0.003) and dried fruit intake (OR: 0.522; 95% CI: 0.311–0.875; p = 0.014) was causally correlated with the risk of CRC. No other significant relationships were obtained. The sensitivity analyses proposed the absence of heterogeneity or pleiotropy, demonstrating the reliability of the MR results.ConclusionThis study indicated that alcoholic drinks were associated with an increased risk of CRC, while non-oily fish intake, fresh fruit intake, cereal intake, and dried fruit were associated with a decreased risk of CRC. This study also indicated that other dietary factors included in this research were not associated with CRC. The current study is the first to establish the link between comprehensive diet-related factors and CRC at the genetic level, offering novel clues for interpreting the genetic etiology of CRC and replenishing new perspectives for the clinical practice of gastrointestinal disease prevention.
BACKGROUND:This study aims to evaluate the diagnostic efficacy of colonic transit test (CTT) in cases of constipation associated with functional defecation disorders (FDD) within the Chinese population. METHODS:A retrospective analysis was conducted involving 202 patients diagnosed with functional constipation, who underwent CTT, high-resolution anorectal manometry, and balloon expulsion test. Participants were categorized based on the Rome IV criteria, comprising 103 patients with FDD and 99 without. The study examined the symptomatic characteristics of both groups and assessed the diagnostic utility of CTT in identifying constipation with FDD. RESULTS:The predominant symptom reported among individuals with chronic functional constipation was excessive straining, observed in 69.3% of cases. The incidence of hard stool passage and feelings of incomplete evacuation were significantly greater in the FDD group compared to the non-FDD group (47.6% vs. 31.3%, p = 0.018 and 50.5% vs. 25.3%, p = 0.001, respectively). The presence of three or more rectosigmoid (RS) residual markers and a transit index of 40% or greater demonstrated moderate diagnostic value for FDD, characterized by low sensitivity(44.7% and 47.6%) but high specificity(76.8% and 75.8%). The RS residual markers were effective in differentiating between FDD and normal transit constipation, but not effectively distinguish between FDD and slow transit constipation. CONCLUSIONS:The presence of RS residue serves primarily as an exclusionary criterion for diagnosing FDD. In cases of slow transit constipation, but not normal transit constipation, it is imperative to conduct multiple kinetic assessments to accurately differentiate between FDD and other types of constipation.
BACKGROUND:Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS:Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS:Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION:MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.
目的 探讨结直肠肿瘤性病变患者内镜黏膜下剥离术(ESD)后息肉样瘢痕结节(PNS)的临床特点.方法 选择行ESD并整块切除、R0切除的结直肠肿瘤性病变患者348例,术后间隔3、6、12个月行结肠镜检查,观察创面愈合情况,出现PNS时需行病理活检检查,比较ESD后PNS患者与正常愈合患者的基本资料.结果 348例患者中有27例(7.76%)出现PNS,均表现为术区原位突出于肠道的息肉样隆起,组织呈红色,质地柔软,病理结果均提示为炎症增生组织,无恶性肿瘤复发或增生不良征象.ESD后PNS患者与正常愈合患者的性别、年龄、原发灶直径、病理类型比较差异均无统计学意义(P均>0.05),ESD后PNS患者原发部位为左半结肠及直肠的比例高于正常愈合患者(P均<0.05).27例ESD后PNS患者随访(33.26±15.10)个月,其中随访时间>36个月14例(51.85%),均未发现PNS发生恶性改变.结论 结直肠肿瘤性病变患者ESD后PNS发生率为7.76%,好发于左半结肠和直肠,病理倾向为良性病变.
目的 评估使用人血白蛋白在肝硬化合并肾病综合征患者中的疗效和安全性.方法 回顾性纳入 2018 年 1 月至 2021 年 11 月间因腹水就诊于我院的 101 例肝硬化合并肾病综合征患者.所有患者接受口服利尿剂及静脉注射白蛋白治疗.汇总患者基线资料,评价治疗前后血清白蛋白及肌酐水平变化.治疗前后白蛋白升高水平大于中位值(1.8 g/L)的定义为治疗有反应组,反之定义为无反应组,并分析相关影响因素.结果 治疗结束后,所有患者腹水相关腹胀症状得到临床缓解,治疗过程中无 1 例发生急性肾损伤.32 例患者在出院后 6 个月内因腹水反复住院.治疗后血清白蛋白水平显著升高[(26.5±5.9)g/L vs.(29.9±4.9)g/L,P<0.001],治疗前后血清肌酐水平差异无统计学意义[(111.9±118.4)μmol/L vs.(108.5±87.9)μmol/L,P=0.816].53 例患者归为有反应组,有反应组与无反应组患者在年龄、性别、肝硬化病因、24h 蛋白尿等方面差异无统计学意义.但是,有反应组血清肌酐水平[(84.1±51.2)μmol/L vs.(142.7±158.4)μmol/L,P=0.017]及尿素氮水平[(8.7±5.1)mmol/L vs.(11.8±9.1)mmol/L,P=0.039]明显低于无反应组.多因素分析结果显示,血清肌酐水平是治疗无反应的独立危险因素,危险比为 1.025(95%CI:1.010~1.049,P=0.037).进一步进行相关分析显示,基线白蛋白水平与住院时间(r=-0.340,P= 0.001)、每日白蛋白使用量(r=-0.546,P<0.001)和基线蛋白尿水平(r=-0.654,P<0.001)分别呈负相关.结论 肝硬化合并肾病综合征患者使用静脉人血白蛋白治疗腹水是安全有效的;肾功能影响血清白蛋白水平和对治疗的反应.
[目的]通过对比内镜下微创治疗及外科手术治疗不同直径的胃间质瘤的手术成功率、时间经济成本以及并发症等,分析内镜下切除不同直径的胃间质瘤的有效性及安全性.[方法]收集经病理证实为胃间质瘤且无远处转移的87例患者的临床资料,根据切除方式不同分为内镜组和手术组,每组根据肿瘤直径不同分为r<2 cm亚组及2 cm≤r≤5 cm亚组.对2组患者的临床特征进行分析,并比较2组在不同肿瘤直径下的手术成功率、手术后的住院时长、住院费用、手术持续时间、术中及术后并发症的严重性及发生率等.[结果]在肿瘤直径r<2 cm的患者中,内镜组及手术组的胃间质瘤均成功切除且无术中及术后并发症的发生;在肿瘤直径2 cm≤r≤5 cm的患者中,内镜组有1例因为术中出血较多转外科手术治疗,内镜组的手术成功率为94.12%;手术组的手术成功率为100%,但有1例外科手术后因为吻合口发生了瘘再次行手术进行修补;2组的手术成功率和术中及术后并发症的发生率比较差异无统计学意义(P>0.05).内镜组的手术时间、住院时间及住院费用均小于手术组,2组比较差异有统计学意义(P<0.05).[结论]对于肿瘤直径r≤5 cm且无远处转移的胃间质瘤,内镜下切除能取得较好的临床效果,具有微创、有效、经济等优势,但是对于病变较大或者浸润较深的胃间质瘤,内镜下切除操作难度大,术前需要严格把握适应证,完善术前超声内镜及腹部CT检查,准确评估胃间质瘤的肿瘤直径及浸润深度,必要时可于手术室完成内镜下治疗.
目的 探讨血清γ-氨基丁酸(GABA)、脑源性营养因子(BDNF)、5-羟色胺(5-HT)、去甲肾上腺素(NE)及多巴胺(DA)在胃食管反流病(GERD)中的表达及临床意义.方法 选取100例GERD患者作为GERD组、40例同期健康体检者为对照组,GERD组患者给予药物治疗8周,根据治疗效果分为效果良好组和效果不良组;对照组于体检时、GERD组于治疗前、治疗后(8周时)取外周静脉血,检测血清GABA、BDNF、5-HT、DA、NE、胃动素(MTL)、胃泌素(GAS)、胆囊收缩素(CCK)水平;采用匹兹堡睡眠质量指数(PSQI)、汉密尔顿抑郁量表(HAMD)、焦虑自评量表(SAS)、日常生活能力量表(ADL)评分评估GERD组治疗前后、对照组体检时的睡眠质量、抑郁程度、焦虑状态、日常生活能力;比较GE RD患者治疗前后、效果良好及效果不良组食管括约压力、立位返流时间比、卧位反流时间比、总反流时间;采用Pearson分析GERD患者治疗前GABA、BDNF、5-HT、NE及DA水平与患者食管括约肌压力、立位返流时间比、卧位返流时间比、总返流时间比、MTL、GAS、CCK的相关性.结果 GERD组治疗后血清GABA、BDNF、5-HT、NE、DA、MTL、GAS水平高于治疗前、但低于对照组,血清CCK水平及各量表评分均低于治疗前、但高于对照组(P<0.05);GERD组患者治疗后食管括约压力高于治疗前,立位返流时间比、卧位反流时间比、总反流时间均低于治疗前(P<0.05);30例疗效不良组GERD患者血清GABA、BDNF、5-HT、NE、DA、MTL、GAS水平及食管括约肌压力均低于70例疗效良好组,血清CCK水平、各量表评分、立位返流时间比、卧位反流时间比、总反流时间比均高于疗效良好组(P<0.05);GERD患者治疗前血清BDNF、5-HT、DA水平与MTL、GAS、食管括约肌压力呈正相关,与立位返流时间比、卧位反流时间比、总反流时间比、CCK呈负相关,GABA、NE与MTL、GAS、食管括约肌压力呈正相关,NE与立位返流时间比、CCK呈负相关性,GABA与立位返流时间比、总反流时间比、CCK呈负相关,差异有统计学意义(P<0.05).结论 GABA、BDNF、5-HT、NE及DA水平与胃内激素MTL、GAS、CCK的合成分泌及胃动力相关指标关系密切,这些神经递质可能参与GE RD的发生和发展过程.
Objective:To evaluate the feasibility and effectiveness of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD).Methods:A total of 36 patients with gastrointestinal tumors at different sites who underwent MAG-ESD in the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to October 2022 were enrolled. The anchor success rate, en bloc resection rate, the anchor time, the procedure time, and the complication incidence were observed and analyzed.Results:Among the 36 patients, there were 9 lesions in stomach, 2 in duodenum, 6 in cecum and 19 in colorectum. Thirty-five (97.2%) patients successfully underwent magnetic anchor, and en bloc resection of lesions were completed. No adverse events such as bleeding or perforation occurred. The anchor time and procedure time was 4.0 (2.0-9.5) min and 36 (16-82) min, respectively.Conclusion:MAG-ESD is feasible and effective for gastrointestinal tumors at different sites, with a high anchor success rate and en bloc resection rate, and shorter operation time, especially for difficult submucosal dissection.
Abstract Disulfidptosis, a new cell death process, is tightly linked to the tumor appearance and development. This research established a five-gene disulfidptosis-related signature (DRS) model and a nomogram to comprehensively assess patient prognosis in HCC patients. We identified two clusters, low DRS score group and high DRS score group, significantly different in overall survival and tumor microenvironment (immunoassay and mutational profile). Moreover, HCC patients in high DRS score group responded less favorably than those in low DRS score group to the current first-line therapies (TACE and sorafenib) but were more sensitive to most standard chemotherapy drugs suggesting that patients who are resistant to first-line medications may benefit from trial use of traditional chemotherapy medicines. As well, in vitro experiments showed that a path for the treatment of HCC patient with a worse prognosis may be provided by the ability of phloretin to cause the death of high SLC7A11 expression HCC cells.
Background: This study is part of a larger research effort to explore the molecular mechanism of hepatocellular carcinoma, reduce drug resistance and seek new targets. Objective: The objective of this study is to investigate the effect and mechanism of fibroblast growth factor receptor inhibitor AZD4547 on Sorafenib-resistant hepatoma cells. Methods: First, we constructed a Sorafenib-resistant hepatoma cell line Huh7R. Different groups of Huh7R cells were treated with Sorafenib, AZD4547, Sorafenib combined with AZD4547, and normal saline. The cell viability was detected by Cell Counting Kit-8. Then Fibroblast growth factor receptor and Toll-like receptor 4 were detected by Western blot, as well as the LC3 II/I, Beclin1, and P62. In addition, we used the autophagy inhibitor 3-methyladenine to identify the mechanism of AZD4547 combined with Sorafenib for inducing Sorafenib-resistant hepatoma cell death. Results: We find that AZD4547 combined with Sorafenib significantly inhibited the viability of Sorafenib-resistant hepatoma cell Huh7R. As for its mechanism, AZD4547 was able to inhibit fibroblast growth factor receptor activity, promote autophagy and regulate immunity. AZD4547 increased LC3 II/I, Beclin1, and Toll-like receptor 4 proteins, and decreased P62 protein level in Huh7R cells significantly when given in combination with sorafenib. Furthermore, 3-methyladenine inhibited autophagy and reversed the killing effect of the combination of AZD4547 and Sorafenib on Huh7R cells. Conclusion: The inhibition of fibroblast growth factor receptor activity by AZD4547 can significantly enhance autophagy and immune response, as well as promote the death of Sorafenib-resistant hepatoma cells.
BACKGROUNDCutaneous squamous cell carcinoma (CSCC) is one of the causes of cancer-related death worldwide. Circular RNAs (circRNAs) play a vital role in the pathological process of many malignant tumors. This study aimed to explore the specific role and potential mechanism of circRNA EBF transcription factor 1 (circEBF1) in CSCC.METHODSThe levels of circEBF1, microRNA-1247-5p (miR-1247-5p) and colony stimulating factor 3 (CSF3) were determined by quantitative real-time PCR and Western blot. Cell proliferation was assessed by colony formation assay. Cell migration, invasion and apoptosis were evaluated by Transwell, wound healing, flow cytometry and Western blot assays. Cellular glycolysis, including glucose consumption, lactate production, and ATP level, was detected by commercial kits. The binding relationship between miR-1247-5p and circEBF1 or CSF3 was verified by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA pull-down assay. Xenograft experiment was conducted to analyze tumor growth in vivo.RESULTScircEBF1 and CSF3 were up-regulated, while miR-1247-5p was down-regulated in CSCC tissues and cells. Interference of circEBF1 hindered the proliferation, migration, invasion, and glycolysis of CSCC cells and promoted apoptosis. In addition, circEBF1 sponged miR-1247-5p to regulate CSCC cell development. Also, miR-1247-5p suppressed CSCC cell progression by inhibiting CSF3. Moreover, depletion of circEBF1 blocked CSCC tumor growth in vivo.CONCLUSIONDown-regulation of circEBF1 impeded CSCC progression by regulating the miR-1247-5p/CSF3 pathway, suggesting that circEBF1 might be a promising therapeutic target for CSCC.
目的:探讨影响胃间质瘤危险度分级的相关因素,为临床诊断提供参考.方法:回顾性收集2016年01月至2019年12月于我院接受治疗的87例经手术后病理证实为胃间质瘤患者的相关临床资料,分析其临床特征、病理及免疫组化结果、治疗措施等,为临床实践提供重要依据.结果:胃间质瘤患者多为中年人,其平均年龄为(59.10±12.92)岁.首发症状最常见的为腹部不适.通过单因素分析提示患者年龄、肿瘤大小与首发症状有一定程度的相关性.肿瘤生长部位最常见的为胃底,直径以2~5 cm最常见.免疫组化分析可知CD117、DOG-1、CD34阳性率较高,分别为97.70%、97.70%、97.70%,Vim、SMA、Desmin阳性率较低,分别为50.57%、17.24%、5.75%.通过单因素分析提示年龄、SMA表达、Demsin表达、Ki-67标记指数(labeling index,LI)与危险度分级有一定相关性.87例患者中行开腹手术27例,腹腔镜手术25例,双镜联合8例,内镜下治疗27例,11例术后服用甲磺酸伊马替尼进行靶向治疗,外科手术及内镜手术均未出现围手术期治疗相关死亡.结论:胃间质瘤患者首发症状缺乏特异性,但可能与患者年龄、肿瘤大小有一定关系.临床上确诊还需依赖病理及免疫组化结果,必要时可结合患者年龄、SMA表达、Demsin表达、Ki-67 LI进一步判断危险度.
目的 研究利那洛肽对于便秘型肠易激综合征(IBS-C)和功能性便秘(FC)的短期疗效差异.方法 纳入23例IBS-C患者和25例FC患者,给予利那洛肽每日290 μg 口服,治疗2周.观察每周自主排便次数,治疗第3、7、10、14日评价粪便性状评分、腹部不适和腹胀评分,以及不良反应发生情况.结果 治疗后,2组患者的自主排便次数及粪便性状评分升高(P<0.05),腹部不适评分及腹胀评分下降(P<0.05).治疗开始后7d内,IBS-C组粪便性状评分的增加值高于FC组(P<0.05);治疗7 d后,2组粪便性状评分、腹部不适和腹胀评分比较无显著差异(P>0.05).整个治疗过程中,2组患者排便次数的增加值、腹部不适评分、腹胀评分的降低值无显著差异(P>0.05).IBS-C组发生腹泻3例,FC组1例,发生率组间比较无显著差异(P>0.05).结论 利那洛肽治疗2周对IBS-C和FC患者症状均有改善作用,且治疗初期对IBS-C患者的粪便性状改善更明显.
Objective: To explore and evaluate infection control measures of preventing cross-contamination of novel coronavirus during gastrointestinal endoscopy treatment Methods: According to the hospital's infection control requirements and related documents, infection control measures were formulated and implemented by combining with our actual clinical situation, including the management of the endoscope room, management and protection of patients and endoscopists Then, we evaluated the effect of these measures Results: From January 25 to March 10, 2020, a total of 71 patients (53 males and 18 females) completed gastrointestinal endoscopy treatment, with an average age of 54 years (28-81 years) There were 36 (50 7%) cases of emergency treatment All patients had been kept in quarantine for about 14 days (24±13), and no cross-contamination of novel coronavirus occurred Conclusion: During the novel coronavirus infection epidemic period, reasonable and effective measures should be taken to minimize the risk of infection in doctors and patients The endoscope center should strengthen preoperative screening and management of patients, master indications of endoscopic procedures, complete endoscopists' management and protection work, strictly follow the specifications of sterilizing gastrointestinal endoscopes, and construct the layout of three zones and two passages