Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by a significant unmet clinical need for more effective and tolerable therapies. This study explores the therapeutic potential and underlying mechanisms of electroacupuncture (EA) at the Baliao acupoints in a dextran sulfate sodium (DSS)-induced UC rat model. EA treatment significantly alleviated colitis symptoms, restored colon length, and enhanced gut barrier integrity by upregulating tight junction proteins (ZO-1/occludin). Mechanistically, EA activated cholinergic neurons in the dorsal root ganglion (DRG), increased the prevalence of α7nAChR (alpha 7 nicotinic acetylcholine receptor)-positive M2 macrophages in the colon, and elevated local acetylcholine levels. These effects were abolished by the α7nAChR antagonist methyllycaconitine (MLA), confirming the critical role of α7nAChR-mediated cholinergic signaling. Additionally, EA modulated gut microbiota composition, promoting beneficial bacteria (eg Lactobacillus) and suppressing pathogenic species. Heart rate variability analysis indicated enhanced vagal activity post-EA. Collectively, these findings demonstrate that EA at the Baliao acupoints alleviates experimental UC via α7nAChR-dependent facilitation of M2 macrophage polarization and restoration of a healthy gut microbiota, highlighting a promising neuromodulation-based approach for UC treatment.

BACKGROUND:Visceral hypersensitivity (VH) is a key pathophysiological feature of irritable bowel syndrome (IBS), contributing to chronic abdominal pain and discomfort. While electroacupuncture (EA) has demonstrated efficacy in alleviating IBS symptoms, the mechanisms underlying its effects at the Baliao acupoint remain unclear. METHODS:In this translational study, we enrolled 40 IBS patients (gender-balanced, aged 30-60 years) who received standardized EA treatment at Baliao acupoints, with pain intensity assessed using visual analogue scale (VAS) scoring. An IBS rat model was established using acetic acid enema combined with restraint stress. Rats received EA at Baliao or sham acupuncture for 2 weeks. Visceral sensitivity was assessed via abdominal withdrawal reflex (AWR), while mast cell (MC) numbers, histamine and substance P (SP) release, and tight junction proteins (ZO-1, occludin) were quantified. Gut-microbiota composition was analyzed by 16S rDNA sequencing, and the alterations of TRPV1+ neuron and MAPK signaling were evaluated via immunofluorescence and Western blot. RESULTS:EA at Baliao significantly attenuated VH in both IBS patients (reduced VAS scores, difference -3.000 ± 0.4264) and rats (lower AWR scores, difference 1.050 ± 0.2630), compared to the sham group. Treatment with EA restored gut microbial diversity, promoting beneficial taxa (Bifidobacterium, Akkermansia) while suppressing pathobionts (Helicobacter, Prevotella). Moreover, EA inhibited MC degranulation, reducing histamine (↓40%, p < 0.01) and SP (↓28%, p < 0.05), and enhanced intestinal barrier integrity via ZO-1/occludin upregulation. Crucially, EA suppressed TRPV1+ neuron activation in the colon and dorsal root ganglia, disrupting MC-neuron crosstalk through TRPV1/MAPK pathway modulation. CONCLUSION:EA (Baliao) alleviates VH by modulating gut microbiota, inhibiting MC activation, and blocking TRPV1 positive neuron mediated signal transmission. These findings highlight its potential as a non-pharmacological therapy for IBS, targeting multiple pathological axes.

Chemoresistance poses a significant challenge in colorectal cancer (CRC) treatment. However, the mechanisms underlying chemoresistance remain unclear. CBX3 promoted proliferation and metastasis in CRC. However, the role and mechanism of CBX3 in chemoresistance remain unknown. Therefore, we aimed to investigate the effects and mechanisms of CBX3 on multidrug resistance in CRC. Our studies showed that higher levels of CBX3 expression were associated with poor survival, especially in groups with progression following chemotherapy. CBX3 overexpression increased Irinotecan and Oxaliplatin resistance, whereas CBX3 knockdown suppressed multidrug resistance in CRC cells. Additionally, CBX3 inhibited ferroptosis associated with multidrug resistance, and the ferroptosis activators prevented CBX3 overexpression-mediated cell survival. RNA sequencing revealed that the NRF2-signaling pathway was involved in this process. CBX3-upregulated NRF2 protein expression by directly binding to the promoter of Cullin3 (CUL3) to suppress CUL3 transcription and CUL3-mediated NRF2 degradation. Moreover, Glutathione Peroxidase 2 (GPX2) was downstream of the CBX3-NRF2 pathway in CRC chemoresistance. ML385, an NRF2 inhibitor, suppressed GPX2 expression, and increased ferroptosis in PDX models. Our study identified CBX3/NRF2/GPX2 axis may be a novel signaling pathway that mediates multidrug resistance in CRC. This study proposes developing novel strategies for cancer treatment to overcome drug resistance in the future.

High-resolution anorectal manometry (HARM) is widely used for diagnosis and assessment of constipation and fecal incontinence. However, limited information is available on HARM-identifiable characteristics in patients with functional anorectal pain (FARP). This study explored the pathogenesis of FARP by investigating their anorectal physiological and psychological characteristics using HARM. 140 patients with FARP who had undergone standard HARM examinations at our institution between January 2021 to January 2023, were retrospectively included for analysis. 110 controls underwent the standard HARM examinations at our institution. Pain was assessed in the FARP group using the visual analog scale (VAS) and psychological status using the Hamilton Anxiety and Depression scales. The mean age was 53.8 ± 11.5 years (range 22–80) in the FARP group and 51.03 ± 12.11 years (range 28–75) in the control group. The mean VAS score in the FARP group was 5.57 ± 2.24. Sensation of desire to defecate, sensation of urgency to defecate, and maximum tolerable sensation were significantly lower in the FARP group, compared with the control group (P < 0.05), demonstrating rectal hypersensitivity. The residual anal canal pressure during defecation, anal resting pressure, and maximum squeeze pressure were significantly lower in the FARP group (P < 0.01 vs. controls). The anal resting pressure was positively correlated with these sensory thresholds. In addition, anxiety was detected in 63.8

Functional Anorectal Pain (FARP) is a chronic, functional, nonorganic disorder of the anorectal region, often misdiagnosed as various types of anorectal organic diseases in clinical practice. However, the pathogenesis and diagnostic markers of FARP remain poorly understood. In this study, we recruited 45 FARP patients and 35 healthy subjects to investigate the microbial and metabolomic profiles associated with FARP progression. Anorectal manometry was utilized to determine changes in anal pressure, revealing a significant decrease in FARP patients' anal resting pressure and maximum anal squeeze pressure. Through 16S rRNA gene sequencing and metabolomics analysis, we identified specific microbial genera, including Propionibacterium, Ruminococcus2, and Bilophila, and specific metabolite profiles, including Gentisic acid, 2-Naphthalenethiol, 2-Furancarboxaldehyde, Benzoic acid, Allose, and (S)-3-Amino-5-methylhexanoic acid, that were closely correlated with FARP. In-depth analysis revealed that the Phospholipase D (PLD) signaling pathway exhibited significant differences in FARP. Additionally, serum cortisol levels were found to be significantly elevated in FARP patients. These findings provide new insights into the anorectal manometry features, gut microbiota, and serum metabolome associated with FARP, potentially contributing to improved clinical diagnosis and therapeutic strategies for FARP.

功能性便秘(FC)是临床上常见的一种消化系统疾病,可引发一系列疾病,因此对该疾病的预防和治疗具有重要意义.干酪乳杆菌是经长期验证对人体无毒副作用,且被广泛用于保健食品生产的益生菌,其对缓解FC有较好的效果.本文从干酪乳杆菌的作用、干酪乳杆菌治疗FC的应用及机制等方面进行综述,以期为FC的治疗方向及干酪乳杆菌用于缓解便秘的机制研究提供思路.

慢性内脏痛(chronic visceral pain,CVP)是一种主要涉及胸部、腹部或骨盆区域的内脏器官引起的疼痛.与躯体痛不同,内脏痛发生部位深,定位不明确,缺乏典型的临床表现.由于其病因及病理机制尚不清楚,相关临床治疗方法有限,且疗效不一.目前一般认为其机制可能与脑肠互动异常、急慢性炎症、内脏痛觉过敏、中枢敏化、神经递质异常、缺血、压力等有关.因此本文基于脑肠轴研究参与慢性内脏疼痛的相关作用机制,从肠道微生物、脑肠肽、炎症因子、功能检查学等方面概述慢性内脏痛的可能病因及病理机制,旨在为慢性内脏痛治疗寻求新的治疗靶点和方案.

Systemic immune activation and excessive inflammatory response, induced by intestinal barrier damage, are the major characteristics of inflammatory bowel disease (IBD). Excessive apoptotic cell accumulation leads to the production of a large number of inflammatory factors, further aggravating IBD development. Gene set enrichment analysis data showed that the homodimeric erythropoietin receptor (EPOR) was highly expressed in the whole blood of patients with IBD. EPOR is specifically expressed in intestinal macrophages. However, the role of EPOR in IBD development is unclear. In this study, we found that EPOR activation significantly alleviated colitis in mice. Furthermore, in vitro, EPOR activation in bone marrow-derived macrophage (BMDMs) promoted microtubule-associated protein 1 light chain 3B (LC3B) activation and mediated the clearance of apoptotic cells. Moreover, our data showed that EPOR activation facilitated the expression of phagocytosis- and tissue-repair-related factors. Our findings suggest that EPOR activation in macrophages promotes apoptotic cell clearance, probably via LC3B-associated phagocytosis (LAP), providing a new mechanism for understanding pathological progression and a novel potential therapeutic target for colitis.

目的 系统评价骶神经刺激(SNS)治疗功能性肛门痛的临床疗效.方法 计算机检索中国知网、万方、中国生物医学文献数据库、PubMed、Web of Science数据库,查找有关SNS治疗功能性肛门痛的临床研究.系统评价SNS对患者疼痛评分(VAS)及测压变化的影响,采用Revman5.3进行Meta分析.结果 共纳入5篇研究,共428例患者,其中SNS组339例,对照组89例.Meta分析结果显示:SNS可以降低VAS(SMD=-2.59,95％CI-4.81～-0.38,P=0.02),降低初始感觉阈值(SMD=-1.14,95％CI-1.41～-0.86,P=0.000),降低持续感觉阈值(SMD=-0.43,95％CI-0.69～-0.18,P=0.001),降低最大耐受量(SMD=-1.44,95％CI-1.72～-1.16,P=0.000),在静息压与收缩压的变化上,差异无统计学意义.敏感性分析显示静息压与收缩压的显著性均发生了较大改变,结果不稳定.结论 SNS可以减轻功能性肛门痛患者的疼痛与改善直肠感觉.但仍需更多高质量、大样本的随机对照试验进一步论证.

慢性疼痛是一类病因和发病机制复杂的难治性疾病.慢性疼痛的治疗方法主要包括药物、微创介入、手术、射频消融等,但疗效有限,同时伴有较大风险.近年来,重复经颅磁刺激(rTMS)技术逐渐成为临床极具潜力的治疗手段.rTMS通过利用脉冲磁场作用于大脑中枢神经系统,改变大脑皮层神经细胞的膜电位,使大脑中枢神经系统产生感应电流,影响脑内代谢和神经电活动,引起颅内一系列生理、生化反应,是一种安全无创的绿色治疗方法.rTMS已被医学界明确为慢性疼痛的有效治疗手段.因此,本文主要对rTMS治疗慢性疼痛的研究进展做了如下综述.

Abstract Background Inflammatory bowel diseases, consisting of Crohn’s disease and ulcerative colitis constitute chronic inflammatory conditions that may compromise the whole gastrointestinal tract as well as the colonic mucosa. Currently, there are no curative interventions for IBD, and all available treatments have side effects that limit their use. Adipose-derived stem cell (ADSC) treatment is a prospective treatment option for IBD. Previous findings indicated that ginsenoside (Rg1) dampened inflammatory diseases like colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg ratio. The purpose of this work was to investigate whether Rg1 can increase the influence of ADSC in a mouse model of colitis triggered by dextran sulfate sodium (DSS). Methods ADSC was intravenously inoculated into mice with DSS-triggered colitis, while Rg1 was delivered via oral gavage. Colon inflammation was assessed via body weight, colon length along with H&E staining. Serum cytokine levels were measured using ELISA. Besides, flow cytometry was adopted to determine the percentage, as well as FMI of immune cells in the spleen. The effects of simultaneous Rg1 and ADSC treatment on TLR4-MyD88 signaling were assessed via immunofluorescence. Results Rg1 and ADSC effectively alleviated the impacts of colon inflammation, weight loss, and colon length reduction along with histological score. Treatment with Rg1 and ADSC reduced serum levels of the proinflammatory cytokines, IL-1β, TNF-α, IL-6, IL-4, and IL-17A and upregulated the level of immunosuppressive cytokine, IL-10. Compared with ADSC or Rg1 alone, combined treatment with Rg1 and ADSC significantly improved the structure of microbial community. Additionally, treatment with Rg1 plus ADSC selectively elevated the level of splenic regulatory T (Treg) cells and downregulated the proportion of T helper type 17 (Th17) cells, indicating restoration of intestinal homeostasis. Besides, we established that the combination of ADSC + Rg1 restored immunological balance more effectively than either ADSC or Rg1 alone, illustrating that Rg1's modulatory function on the gut microbiota may boost the impact of ADSCs in restoration of the immune balance. ADSC combined with Rg1 might downregulate the expression of TLR4 and MyD88, thereby suppressing TLR4-MyD8 signaling. The immunofluorescence results also suggested that co-therapy with Rg-1 and ADSC may optimize treatment strategies of IBD. Conclusions Here, we find that the combination of Rg1 and ADSC alleviates DSS-induced colitis in a mouse model more efficiently than ADSC alone, indicating that Rg1 enhances the effect of ADSC against colitis.

功能性便秘是肛肠科常见疾病之一,严重影响患者的生活质量.直肠动力、感觉功能异常是其主要发病机制之一,而肛管直肠高分辨率测压作为一种非侵入性、客观的检测手段,能有效检测肛门直肠运动和感觉功能,是研究肛管直肠生理功能和指导肛肠疾病诊治的重要手段,特别是在功能性便秘的机制、诊断及治疗方面有着独特的优势.近10年来,肛管直肠高分辨率测压的研究不断涌现新的成果.本文就肛管直肠高分辨率测压在功能性便秘上的最新研究进展做一综述.

Neuromodulation refers to the method that plays an exciting, inhibitory or regulatory role on neurons or nerve signal transduction through various forms of stimulation, so as to strengthen neural connections and enhance neuroplasticity. Neuromodulation is widely used in colorectal anal diseases, including sacral nerve stimulation, tibial nerve stimulation, vagus nerve stimulation, pudendal nerve stimulation and other treatments. There are few studies on the pudendal nerve stimulation, and the understanding is still unclear. Therefore, this paper reviews application and research progress of pudendal nerve modulation.

Abstract Background Inflammatory bowel diseases (IBDs) including Crohn's disease and ulcerative colitis are chronic inflammatory disorders that can affect the entire gastrointestinal tract and the colonic mucosa, no medical or surgical cure for IBD, and all have side effects that limit their use, exhibit a high necessity for new therapeutic strategies. Adipose-derived stem cells (ADSC) therapy represents a promising option for the treatment of IBD. Rg1 Previous study indicated that ginsenoside (Rg1) can ameliorate inflammatory disease such as colitis by inhibiting the binding of LPS to TLR4 on macrophages and restoring the Th17/Treg imbalance [1]. In this study, we investigated whether Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model. Methods Mice with dextran sulfate sodium-induced colitis were injected intravenously with ADSC and administered with Rg1 by gavage. Body weight change, colon length, H&E staining were used to evaluate colon inflammation severity in a DSS-induced colitis Serum were collected for Cytokine detection by ELISA. The proportion and FMI of immune cells in spleen were analyzed by flow cytometry. Stool DNA was extracted for 16S rRNA gene sequencing. Results Rg1 and ADSC showed significantly ameliorated colon inflammation, such as body weight loss, shortening of colon length, histology score. Rg1 and ADSC treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, IL-4 and IL-17A and upregulated the immunosuppressive cytokine IL-10 in serum. We observed that the structure of the microbial community in Rg1 + ADSC group were significantly changed compared to that of ADSC and Rg1 groups, respectively. Additionally, Rg1 and ADSC treated selectively upregulated the percentage of spleen regulatory T (Treg) cells as well as downregulated the frequency of T helper type 17 (Th17) cells, ameliorating the Treg/Th17 balance to maintain intestinal homeostasis. Furthermore, we found the combination of ADSC + Rg1 groups showed more efficiently than that of ADSC and Rg1 alone, respectively, which indicates that the regulation effect of Rg1 on gut microbiome may enhance the effects of ADSCs in restoring immune balance. Conclusions Our study indicated that the combination of Rg1 and ADSC can alleviate dextran sulfate sodium-induced colitis more efficiently than that of ADSC alone, Rg1 can enhance the effect of ADSC on DSS-induced colitis in a mouse model.

间充质干细胞是一种多能干细胞,具有来源广泛、支持造血、调节免疫、自我更新、高度增殖、定向分化等优点,是生命科学领域的一大研究热点.近年来,一些学者就中药及其提取物对间充质干细胞的影响进行了一系列的研究,人参皂苷Rg1就是其中之一.相关研究表明,人参皂苷Rg1作用于间充质干细胞能够促进增殖、抑制凋亡、促进旁分泌、诱导分化.对间充质干细胞与人参皂苷Rg1的基本特性、人参皂苷Rg1对间充质干细胞的作用及其应用等方面的最新进展做一综述,希望为今后的研究奠定基础.

针灸疗法是临床上常用的一种中医外治疗法.大量的研究证实,用针灸疗法治疗溃疡性结肠炎可取得显著的疗效,且安全性较高.但其相关作用机制目前尚未完全明确.本文主要是介绍近年来有关用针灸疗法治疗溃疡性结肠炎作用机制的研究进展.

肛瘘的外科治疗理念经历了从毁损性切除到修复再到重建、再生的过程.目前,肛瘘的治疗原则是在保证疗效的基础上追求肛门功能保护,因此,能够最大限度保护括约肌功能的微创治疗的发展前景十分广阔.本文通过检索PubMed、Cochrane Library CENTRAL、Embase、CK-NI、万方、维普等数据库中关于肛瘘微创治疗的文章,并进行综述.

[目的]评价益气养血汤内服治疗功能性肛门直肠痛(FAP)的临床疗效.[方法]选取40例FAP患者,采用随机数字表法分为观察组和对照组各20例.观察组采用益气养血汤加温水坐浴治疗;对照组采用温水坐浴.2周为1个疗程,共2个疗程.分析比较两组患者治疗前后疼痛视觉模拟评分(VAS)、焦虑及抑郁自评分(SDS)、SF-36生活质量评分、治疗效果评估.采用SPSS 24.0软件进行统计分析.[结果]观察组治疗总有效率85.00％显著高于对照组的55.00％(P<0.05);观察组治疗后VAS评分显著低于对照组及治疗前(P<0.05);观察组及对照组治疗后焦虑及抑郁自评分(SAS、SDS)均显著低于治疗前,但观察组评分更低(P<0.05);观察组及对照组治疗后SF-36生活质量评分均显著高于治疗前,但观察组评分更高(P<0.05).[结论]益气养血汤口服治疗功能性肛门直肠痛能够取得良好的临床疗效,改善患者预后.

炎症性肠病( inflammatory bowel disease,IBD)是多因素导致的复杂的慢性复发性疾病. 受饮食以及环境等复杂因素的影响,近年来全球的发病呈现上升趋势. IBD传统高发区为北美,北欧和西欧. 在过去二十年中,东欧和亚洲各地的发病率也在不断上升[1]. 如今虽然出现了治疗IBD的新型药物,但仅能实现和维持黏膜炎症及症状的缓解,仍未彻底改变和阻断结肠炎症病程. 间充质干细胞( mesen-chymal stem cell,MSCs)是一种多功能干细胞,它可以从大多数机体组织中分离出来. 除了参与造血和具有多谱系分化、迁移至受损组织的能力外,还发挥强大的免疫调节作用. 已有临床试验证实MSC可以有效治疗IBD[2-5] ,但治疗机制尚有争议. 本文就其作用机制进行初步探讨.