IntroductionAs a vascular-related disease, hemorrhoids cause pathological changes, such as abnormal dilation in the anorectal vascular plexus (AVP), which may be closely related to injury to vascular endothelial barrier function (VEBF). Elevated deoxycholic acid caused by a high-fat diet can impair intestinal barrier function. However, the effect of VEBF impairment in AVP caused by DCA is unclear. The aim of our study was to investigate the effects of DCA and GYY4137 on the VEBF in AVP and to explore the pathogenesis of hemorrhoids and new treatment ideas.MethodsA HUVECs monolayer model and mouse model were generated with a high DCA concentration and used to investigate the effect of GYY4137 on SDC-induced VEBF disruption in AVP and the underlying mechanism.ResultsIn the HUVECs monolayer model, DCA significantly increased the permeability of the monolayer and altered the distribution of tight junction proteins (TJPs) by increasing the levels of myosin light chain kinase and myosin light chain phosphorylation. GYY4137 pretreatment significantly improved DCA-induced VEBF dysfunction. GYY4137 can also increase resistance to SDC-induced VEBF injury and improve the distribution of TJPs in the AVP in mouse model.ConclusionGYY4137 can improve the distribution of TJPs by inhibiting the activation of the MLCK-P-MLC2 signaling pathway induced by DCA, thereby protecting the VEBF in AVP, which may be applied to hemorrhoids therapy in the future.
Schwannomas are usually benign tumors typically found in the head, neck, and extremities, with approximately 3% originating in the retroperitoneum. In this case, a young male presented with incidental masses in the left kidney and retroperitoneum. Abdominal pelvic enhanced computerized tomography (CT) revealed a tumor apparently originating from the left kidney, along with a retroperitoneal mass suspected to be a metastatic lymph node. Subsequently, a radical nephrectomy of the left kidney and retroperitoneal mass resection was performed. Pathological examination confirmed the left kidney mass as renal clear cell carcinoma and the retroperitoneal mass as schwannoma. The patient recovered uneventfully and was discharged from the hospital. A 6-month postoperative follow-up showed no evidence of recurrence. Preoperative diagnosis of schwannomas concurrent with other concurrent malignancies in rare sites, such as the retroperitoneum, is challenging due to their rare and non-specific radiological features. Although retroperitoneal schwannomas are rare, they should be considered in the differential diagnosis during CT examinations for renal cancer. Additionally, the advantages of a multidisciplinary team approach should be utilized in tumor management.
IntroductionNumerous studies have revealed that a long-term high-fat diet can raise intestinal deoxycholate acid concentration, which can harm intestinal mucosal barrier function in several ways. This study aims to verify the protective effect of GYY4137, as a slow-releasing H2S donor, on microbiome disturbance and the chronic injury of the intestinal mucosal barrier function caused by sodium deoxycholate.MethodsCaco-2 monolayer and mouse models were treated with a relatively high concentration of sodium deoxycholate (1.0 mM and 0.2%, respectively) for longer periods (32 h and 12 weeks, respectively) to understand the effects of GYY4137 on sodium deoxycholate–induced chronic intestinal barrier dysfunction and its fundamental mechanisms.ResultsA relatively long period of sodium deoxycholate treatment can remarkably increase the intestinal barrier permeability, alter the distribution and expression of tight junction proteins and generate the production of pro-inflammatory cytokines (TNF-α and IL-1β) in the Caco-2 monolayers and mouse models. Moreover, it can activate the MLCK-P-MLC2 pathway in the Caco-2 monolayers, which was further confirmed using RNA sequencing. The body weight, intestinal barrier histological score, and TUNEL index of sodium deoxycholate-treated mice worsened. In addition, an induced microbiome imbalance was observed in these mice. The above variations can be reversed with the administration of GYY4137.ConclusionThis study demonstrates that GYY4137 ameliorates sodium deoxycholate–induced chronic intestinal barrier injury by restricting the MLCK-P-MLC2 pathway while elevating the expression level of tight junction proteins, anti-apoptosis and maintaining the microbiome’s homeostasis.
IntroductionThe study aims to develop a prediction model to differentiate transient ischemia from irreversible transmural necrosis in closed-loop small bowel obstruction (CL-SBO).MethodsA total of 180 participants with CL-SBO between January 2010 and December 2019, of which 122 had complete radiologic data, were included to investigate the significant clinical and imaging characteristics for differentiating patients with necrosis from transient ischemia. A logistic regression model was developed and validated.ResultsIn a multivariate analysis, the American Society of Anesthesiologists physical status classification system >2 is the independent predictor for transmural necrosis. Another multivariate analysis, including clinical and imaging factors, revealed that the imaging sign of mesenteric vessel interruption was an independent risk factor for necrosis. The diagnostic model developed using these two factors has excellent performance among the validation sets, with an area under the curve of 0.89.ConclusionThe diagnostic model and innovative imaging signs have substantial potential in solving this complex clinical problem.
Background:The associations between preoperative transfer to hemodialysis (HD) and postoperative outcomes in patients on chronic peritoneal dialysis (PD) remain unknown. We conducted this retrospective cohort study to investigate whether preoperative HD could influence surgical outcomes in PD patients undergoing major surgeries.Methods:All chronic PD patients who underwent major surgeries from January 1, 2007, to December 31, 2020, at Peking University First Hospital were screened. Major surgery was defined as surgical procedures under general, lumbar or epidural anesthesia, with more than an overnight hospital stay. Patients under the age of 18, with a dialysis duration of less than 3 months, and those who underwent renal implantation surgeries and procedures exclusively aimed at placing or removing PD catheters were excluded. Patients involved were divided into either HD or PD group based on their preoperative dialysis status for further analysis.Results:Of 105 PD patients enrolled, 65 continued PD, and 40 switched to HD preoperatively. Patients with preoperative HD were significantly more likely to develop postoperative hyperkalemia. The total complication rates were numerically higher in patients undergoing preoperative HD. After adjustment, the incidence of postoperative hyperkalemia or any other postoperative complication rates were similar between groups. There were no differences in long-term survival between the two groups.Conclusions:It does not seem indispensable for PD patients to switch to temporary HD before major surgeries.
Objectives This research aims at evaluating the quality of anal cancer and its precancerous lesions-related videos on YouTube.Design Cross-sectional survey design.Setting USA.Participants The top 150 videos on YouTube were selected for analysis based on three search terms. The duplicate, irrelevant, commercial, operation-related and audio-free videos were excluded. Finally, 105 relevant videos were included.Methods We assessed the completeness of video content from six dimensions and marked the men having sex with men (MSM)-related videos. To measure the video quality, DISCERN, Journal of the American Medical Association (JAMA) Benchmark Criteria, Patient Education Materials Assessment Tool (PEMAT) and Global Quality Scale (GQS) were used. The correlation between DISCERN classification and duration, JAMA, PEMAT and GQS scores were recorded.Results The video content was mainly about the management of the disease (mean score 1.086). Overall, the quality of videos uploaded by the non-profit organisation was relatively high. A correlation existed between each other of the JAMA, DISCERN and GQS scores (p<0.001). Moreover, they were positively correlated with video duration and PEMAT scores (p<0.001).Conclusions Although the overall quality of information about anal cancer and its precancerous lesions videos on YouTube is acceptable, it might not fully meet the health information needs of patients. Therefore, they should exercise caution when using YouTube as a source of anal cancer-related information, especially the MSM population.
Background: Patients transferred from the respiratory intensive care unit (ICU) can experience post eintensive care syndrome (PICS), which comprises cognitive, psychological, and physical disorders that seriously affect the quality of life. Therefore, it was necessary to explore the incidence of and the risk factors for PICS among respiratory ICU patients. Objectives: This study evaluated PICS among respiratory ICU patients and explored the risk factors for PICS. Methods: This cross-sectional, prospective study was performed at one hospital in China. Using convenience sampling, 125 respiratory ICU patients from August 2018 to June 2019 were recruited for the study. The Mini-Mental State Examination, Confusion Assessment Method for the Intensive Care Unit, Hospital Anxiety and Depression Scale, Medical Research Council Scale, activities of daily living scale, Pittsburgh Sleep Quality Index, and the 14-item fatigue scale were used to comprehensively assess the patients' cognitive status, psychological status, and physiological status when entering the ICU and 2 weeks after leaving the ICU. Factors affecting PICS were measured using researcher-created questionnaires of patients' general information and disease-related information. Results: Fifteen patients were lost to follow-up. Fifty-nine patients had PICS (incidence rate, 53.6%). Logistic regression showed that risk factors for PICS were age, invasive mechanical ventilation, noninvasive ventilator-assisted ventilation, and coronary heart disease (P < 0.05). Conclusion: The PICS incidence was high. Older age, longer invasive mechanical ventilation times, longer noninvasive ventilator times, and coronary heart disease were risk factors for PICS. ICU medical workers in China should pay more attention on PICS, know the risk factors, and implement preventive measures. (c) 2022 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.
Background: Extramammary Paget’s disease (EMPD) is a rare malignant cutaneous tumour that is commonly located in anogenital regions. The diagnosis of the disease is always delayed, and treatment is usually troublesome. This study aims to summarise the clinicopathological characteristics and the risk factors of prognosis for EMPD in anogenital regions, potentially providing evidence for the diagnosis and treatment of anogenital EMPD. Methods: 688 patients were sourced from the Surveillance, Epidemiology and End Results (SEER) program between 1992 and 2021. In total, 176 participants from our centre from between 2011 and 2021 were included to investigate the characteristics and prognosis for EMPD in anogenital regions. Results: From the SEER program data, patient age of 65 years or older, metastasis of lymph nodes, Spanish-Hispanic-Latino race, diameter exceeding 10cm and lesions located anally were revealed as independent risk factors for shorter cancer-specific survival (CSS). However, the data from our centre highlighted that metastasis of lymph nodes and tumours extending through the epidermis are independent risk factors of shortened progression-free survival (PFS) and CSS of anogenital EMPD. Conclusion: This synthesised study revealed that some characteristics are regarded as risk factors for poor clinical prognosis, which have potential value in formulating more normative and effective strategies for patients with EMPD in anogenital regions.
肛门鳞状细胞癌(anal squamous cell carcino?ma,ASCC)是肛门癌最常见的病理类型,作为一种相对少见的消化道恶性肿瘤,近年来ASCC发病率及死亡率呈上升趋势[1].肛门上皮内瘤变(anal intraep?ithelial neoplasia, AIN)被认为是ASCC的癌前病变[2-4],根据病灶区域鳞状上皮发生非典型增生的不同程度可将其分为AIN 1~3级[4],约有10%的AIN 3级患者在确诊后的5年内发展为ASCC[5],而AIN的发病率年增长率达10%~15%[3].
紧密连接蛋白(TJP)是肠黏膜机械屏障的重要组成部分,TJP表达量异常将会引起肠黏膜屏障功能损伤,导致克罗恩病、溃疡性结肠炎、肠易激综合征等疾病的发生.微小 RNA(miRNA)在转录后水平广泛参与入体蛋白表达的调控,其中包含TJP.笔者回顾近年的相关文献,将引起miRNA表达异常的因素分为细胞因子、肠道疾病和其他3种情况,针对miRNA对肠黏膜TJP表达调节的相关机制进行综述,提出未来需要进一步研究和努力的方向,以期为临床诊断和治疗肠黏膜TJP表达异常相关性疾病提供思路.
BackgroundGastric cancer and gastro-esophageal adenocarcinoma are geographically heterogeneous diseases. Previous studies suggested that Asian and Western patients with late-stage gastric or gastro-esophageal adenocarcinoma possess distinct survival outcomes. However, the interregional differences of multiple systemic therapies in unresectable diseases have not been comprehensively described.Materials and MethodsWe searched PubMed-MEDLINE, Embase, Web of Science and Cochrane Library from inception to 31 October 2021 and reviewed major conference abstracts for controlled trials of systemic therapies in unresectable gastric or gastro-esophageal adenocarcinoma that reported hazard ratios stratified by geographical region. The primary measurements were overall survival and progression-free survival. The pooled hazard ratios and 95% confidence intervals for overall survival and progression-free survival in Asian and Western populations were calculated using a random effect model. A linear regression model was adopted to compare the overall survival and progression-free survival between Asian and Western patients.ResultsA total of 9033 patients from 20 studies were included for analysis. Immunotherapy was associated with an improvement in the overall survival for both Asian (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) and Western (hazard ratio, 0.90; 95% confidence interval, 0.81–1.00) patients, with no significant difference between the two groups (P = 0.32). Trends of survival benefit with anti-HER2 therapy and anti-angiogenic therapy versus control were observed in both Asian and Western patients, although statistical significance was not denoted. Subgroup analyses yielded a statistically superior overall survival of Asian versus Western patients in trials that investigated first-line immunotherapy (P = 0.04). Due to the linear regression analyses with scatter plot graphs, Asian patients showed a higher overall survival, but not progression-free survival, than Western patients irrespective of treatment type.ConclusionAsian and Western patients with unresectable gastric or gastro-esophageal adenocarcinoma show similar responses to systemic therapies with limited interregional differences. Exceptionally, first-line immunotherapy could elicit superior survival among Asian populations. In addition, Asian patients with gastric or gastro-esophageal adenocarcinoma display a superior OS compared with Western counterparts.
Background The role of hydrogen sulfide (H 2 S) in cancer biology is controversial, including colorectal cancer. The bell-shaped effect of H 2 S refers to pro-cancer action at lower doses and anti-cancer effect at higher concentrations. We hypothesized that overexpression of cystathionine-beta-synthase (CBS)/H 2 S exerts an inhibitory effect on colon cancer cell proliferation and metastasis. Methods Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8), clone-formation and sphere formation assay. Cell migration was evaluated by transwell migration assay. Intracellular H 2 S was detected by H 2 S probe. Chromatin immunoprecipitation (ChIP) analysis was carried out to examine DNA–protein interaction. Cell experiments also included western blotting, flow cytometry, immunohistochemistry (IHC) and immunofluorescence analysis. We further conducted in vivo experiments to confirm our conclusions. Results Overexpression of CBS and exogenous H 2 S inhibited colon cancer cell proliferation and migration in vitro. In addition, overexpression of CBS attenuated tumor growth and liver metastasis in vivo. Furthermore, CD44 and the transcription factor SP-1 was probably involved in the inhibitory effect of CBS/H 2 S axis on colon cancer cells. Conclusions Overexpression of CBS and exogenous provision of H 2 S inhibited colon cancer cell proliferation and migration both in vivo and in vitro. Molecular mechanisms might involve the participation of CD44 and the transcription factor SP-1.
IntroductionAnal fissure is a common colorectal disease impacting patients' life quality with high incidence. Social media platforms are becoming a kind of health information source nowadays. This study aims to evaluate and compare the quality of anal fissure-related videos on TikTok and YouTube. Materials and methodsOne hundred videos were sourced from TikTok and YouTube, respectively and videos were screened further. The completeness of six types of content within the videos is assessed, including the definition of disease, symptoms, risk factors, evaluation, management and outcomes. Finally, the DISCERN instrument, Patient Education Materials Assessment Tool and Global Quality scale are used to assess video display quality and content. A correlation analysis is undertaken considering the video features, DISCERN, PEMAT and GQS scores. ResultsPhysicians and non-profit organizations contributed almost all video content among selected videos. A statistically significant correlation between DISCERN classification and duration, PEMAT understandability, PEMAT actionability and GQS scores is recorded. DISCERN total scores were significantly positively correlated with video duration, PEMAT understandability, PEMAT actionability and GQS scores. GQS scores were significantly positively correlated with duration, PEMAT understandability and PEMAT actionability scores. For content, the videos mainly described management and symptoms while containing limited information on the disease evaluation, and outcomes. ConclusionsThe sources of uploaders on YouTube are more diverse than TikTok, and the quality of videos is also relatively higher on YouTube. Even so, the video quality of the two platforms still needs to be further improved. Health information without integrity, reliability and practicability impacts patients' disease perception and health-seeking behavior, leading to serious consequences. Much effort must be taken to improve the quality of videos regarding anal fissures on the two platforms, which will facilitate the development of public health education on this issue.
在美国,痔是第三常见的门诊胃肠道诊断,每年有近400万门诊和急诊就诊,常见症状表现为便血、肛门坠痛不适、肛周肿物等[1].痔的发生被认为是多种致病因素共同作用的结果,由于无法具体评估每种因素在痔发生过程中所起作用的比例大小,所以关于痔的发病机制存在多种观点[2-3].有观点认为,痔是一种外周血管性疾病.直肠肛管血管丛(anorectal vascular plexus, AVP)即直肠肛管移行区域的黏膜下血管丛,具有防止肠液溢出肛门的机械性自制作用,因痔患者的AVP通常位于病灶黏膜下,其又被称为"痔血管丛"或"直肠海绵体",在内镜下常表现为迂曲扩张的血管团[4-5].