Mucocele: a rare complication following stapled haemorrhoidopexy.

BACKGROUND: Stapled haemorrhoidopexy (SH) has resulted in a unique collection of procedural complications with postoperative mucocele a particularly rare example. This study is designed to comprehensively describe the characteristics of rectal mucocele and discuss its pathogenesis following SH surgery. METHODS: A database of patients presenting with a rectal mucocele following an SH procedure was established and studied retrospectively. RESULTS: Seven patients (5 males; median age 32 years, range 20-75 years) were identified. All patients complained of variable anal discomfort with 5/7 presenting with inconstant anal pain, 2 with de novo evacuatory difficulty. These cases appeared at a median time of 6 months (range 2-84 months) after SH surgery. CONCLUSION: Rectal Mucocele develops when mucosal fragments become embedded and isolated under the mucosa. It is a preventable complication of SH surgery by ensuring correct purse string placement prior to stapled haemorrhoid excision.

Single-cell RNA sequencing reveals cellular dynamics and therapeutic effects of astragaloside IV in slow transit constipation.

The cellular characteristics of intestinal cells involved in the therapeutic effects of astragaloside IV (AS-IV) for treating slow transit constipation (STC) remain unclear. This study aimed to determine the dynamics of colon tissue cells in the STC model and investigate the effects of AS-IV treatment by single-cell RNA sequencing (scRNA-seq). STC mouse models were developed using loperamide, with subsequent treatment using AS-IV. Colon tissues and feces were collected for scRNA-seq and targeted short-chain fatty acid quantification. We integrated scRNA-seq data with network pharmacology to analyze the effect of AS-IV on constipation. AS-IV showed improvement in defecation for STC mice induced by loperamide. Notably, in STC mice, epithelial cells, T cells, B cells, and fibroblasts demonstrated alterations in cell proportions and dysfunctions, which AS-IV partially rectified. AS-IV has the potential to modulate the metabolic pathway of epithelial cells through its interaction with peroxisome proliferator-activated receptor gamma (PPARγ). AS-IV reinstated fecal butyrate levels and improved energy metabolism in epithelial cells. The proportion of naïve CD4+T cells is elevated in STC, and the differentiation of these cells into regulatory T cells (Treg) is regulated by B cells and fibroblasts through the interaction of ligand-receptor pairs. AS-IV treatment can partially alleviate this trend. The status of fibroblasts in STC undergoes alterations, and the FB_C4_Adamdec1 subset, associated with angiogenesis and the Wingless-related integration (Wnt) pathway, emerges. Our comprehensive analysis identifies perturbations of epithelial cells and tissue microenvironment cells in STC and elucidates mechanisms underlying the therapeutic efficacy of AS-IV.

Stapled transperineal rectovaginal fistula repair for low- and mid-level rectovaginal fistulas: A comparison study with rectal mucosal advancement flap repair.

BACKGROUND: As an innovative treatment, stapled transperineal rectovaginal fistula repair (STR) for rectovaginal fistula (RVF) has demonstrated effectiveness in preliminary reports. This study aims to compare STR with rectal mucosal advancement flap repair (RAF), a widely utilized surgical procedure, for the surgical outcome of the low- and mid-level RVF. METHODS: In this retrospective cohort study, patients with low- and mid-level RVF who underwent STR or RAF were included from both the Sixth Affiliated Hospital of Sun Yat-sen University and Xi'an Daxing Hospital. Among the 99 total patients, 77 underwent STR and 22 underwent RAF. Patient demographics, operative data, and outcomes were collected and analyzed. Recurrence rate and associated risk factors were evaluated. RESULTS: There were no statistically significant differences among patients in terms of clinical characteristics like age, BMI, aetiology, and fistula features. During the follow-up period of 20 months (interquartile range 3.0-41.8 months), a total of 28 patients relapsed, with a significantly lower recurrence rate in the STR group (20.8 %) than in the RAF group (54.6 %) (P = 0.005). In the multivariate Cox analysis, STR was an independent protective factor against recurrence (HR: 0.37, 95%CI: 0.17-0.79, P = 0.01). Logistic regression indicated that there was no statistically significant difference between these two procedures in terms of surgical complications (OR: 0.53, 95%CI: 0.19-1.48, P = 0.23). CONCLUSION: For low- and mid-level RVF, STR may be an alternative option for treatment modality that offers a lower recurrence rate, without observed disadvantage in terms of surgical complication rates.

A frameshift variant in the SIRPB1 gene confers susceptibility to Crohn's disease in a Chinese population.

Background: Crohn's disease (CD), a chronic gastrointestinal inflammatory disease, is increasing in China. With a focus on Han Chinese families with CD, the aim of this study was to find genetic variations that increase CD susceptibility by genome sequencing, genetic association, expression, and functional research. Materials and methods: We performed family-based genome sequencing (WGS) analysis on 24 patients with CD from 12 families and then filtered shared potential causal variants by incorporating association results from meta-analyses of CD GWAS and immunology genes and in silico variant effect prediction algorithms. Replication analyses were performed in an independent cohort including 381 patients with CD and 381 control subjects. Results: There were 92 genetic variants significantly associated with CD in Chinese individuals. Among them, 61 candidate loci were validated in replication analyses. As a result, patients carrying a rare frameshift variant (c.1143_1144insG; p. Leu381_Leu382fs) in gene SIRPB1 had significantly higher risk to develop CD (p = 0.03, OR 4.59, 95% CI 0.98-21.36, 81.82% vs. 49.53%). The frameshift variation induced tyrosine phosphorylation of Syk, Akt, and Jak2, elevated the expression of SIRPB1 at the mRNA and protein levels, activated DAP12, and controlled the activation of NF-κB in macrophages. Additionally, it promoted the synthesis of the pro-inflammatory cytokines IL-1, TNF-, and IL-6. Conclusion: Our results suggest that the rare gain-of-function frameshift variant in SIRPB1 is associated in Han Chinese patients with CD. The functional mechanism of SIRPB1 and its downstream inflammatory pathways was preliminarily explored in CD.

Astragaloside IV improves slow transit constipation by regulating gut microbiota and enterochromaffin cells.

Purpose: Slow transit constipation (STC) is a common gastrointestinal disorder characterized by altered gut microbiota and reduced number of enterochromaffin cells (ECs). Astragaloside IV (AS-IV), a low drug permeability saponin, has showed beneficial effects on patients with STC. However, the specific mechanism by which AS-IV regulates STC remains unclear. In this study, we aimed to investigate the effect of AS-IV on STC and its associated mechanisms involving gut microbiota. Methods: The effect of AS-IV on STC was evaluated on STC mice induced with loperamide. We measured defecation frequency, intestinal mobility, ECs loss, and colonic lesions in STC mice treated with AS-IV. We also analyzed the changes in gut microbiota and metabolites after AS-IV treatment. Moreover, we investigated the relationship between specific gut microbes and altered fecal metabolites, such as 3-bromotyrosine (3-BrY). We also conducted in vitro experiments to investigate the effect of 3-BrY on caspase-dependent apoptosis of ECs and the activation of the p38 MAPK and ERK signaling pathways induced by loperamide. Results: AS-IV treatment promoted defecation, improved intestinal mobility, suppressed ECs loss, and alleviated colonic lesions in STC mice. AS-IV treatment also affected gut microbiota and metabolites, with a significant correlation between specific gut microbes and altered fecal metabolites such as 3-BrY. Furthermore, 3-BrY may potentially reduce caspase-dependent apoptosis of ECs and protect cell survival by inhibiting the activation of the p38 MAPK and ERK signaling pathways induced by loperamide. Conclusion: Our findings suggest that changes in gut microbiota and ECs mediated the therapeutic effect of STC by AS-IV. These results provide a basis for the use of AS-IV as a prebiotic agent for treating STC. The specific mechanism by which AS-IV regulates gut microbiota and ECs warrants further investigation.

Association between Dietary Inflammatory Index and Risk of Colorectal Adenomatous Polyps in Kashgar Prefecture of Xinjiang, China.

Malignant colorectal tumors and precancerous lesions are closely associated with chronic inflammation. Specific dietary patterns can increase chronic inflammation in the body, thereby promoting the occurrence of tumors and precancerous lesions. We have conducted a case-control study in Kashgar Prefecture, Xinjiang, China, to explore the association between the energy-adjusted dietary inflammatory index (E-DII) and the risk of colorectal adenomatous polyps (CAP). A total of 52 newly diagnosed patients with CAP and 192 controls at the First People's Hospital of Kashgar Prefecture were enrolled in this study. Dietary information was collected using a food frequency questionnaire. The E-DII was calculated based on dietary data, reflecting an individual's dietary inflammatory potential. Logistic regression models were used to evaluate the relationship between the E-DII and the risk of CAP, with adjustments for potential confounding factors. The results showed that the maximum anti- and pro-inflammatory values of E-DII were -4.33 and +3.48, respectively. Higher E-DII scores were associated with an increased risk of CAP, and this association remained statistically significant after adjusting for age, sex, body mass index, smoking status, and other relevant variables. Notably, a more pro-inflammatory dietary pattern may be related to an increased risk of developing CAP in Kashgar Prefecture.

Corrigendum: Effects of Xiao Chengqi formula on slow transit constipation by assessing gut microbiota and metabolomics analysis in vitro and in vivo.

[This corrects the article DOI: 10.3389/fphar.2022.864598.].

Cancer-associated fibroblasts undergoing neoadjuvant chemotherapy suppress rectal cancer revealed by single-cell and spatial transcriptomics.

Neoadjuvant chemotherapy (NAC) for rectal cancer (RC) shows promising clinical response. The modulation of the tumor microenvironment (TME) by NAC and its association with therapeutic response remain unclear. Here, we use single-cell RNA sequencing and spatial transcriptome sequencing to examine the cell dynamics in 29 patients with RC, who are sampled pairwise before and after treatment. We construct a high-resolution cellular dynamic landscape remodeled by NAC and their associations with therapeutic response. NAC markedly reshapes the populations of cancer-associated fibroblasts (CAFs), which is strongly associated with therapeutic response. The remodeled CAF subsets regulate the TME through spatial recruitment and crosstalk to activate immunity and suppress tumor progression through multiple cytokines, including CXCL12, SLIT2, and DCN. In contrast, the epithelial-mesenchymal transition of malignant cells is upregulated by CAF_FAP through MIR4435-2HG induction, resulting in worse outcomes. Our study demonstrates that NAC inhibits tumor progression and modulates the TME by remodeling CAFs.

Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer.

BACKGROUND: Activation of MEK5 in many cancers is associated with carcinogenesis through aberrant cell proliferation. In this study, we determined the level of phosphorylated MEK5 (pMEK5) expression in human colorectal cancer (CRC) tissues and correlated it with clinicopathologic data. METHODS: pMEK5 expression was examined by immunohistochemistry in a tissue microarray (TMA) containing 335 clinicopathologic characterized CRC cases and 80 cases of nontumor colorectal tissues. pMEK5 expression of 19 cases of primary CRC lesions and paired with normal mucosa was examined by Western blotting. The relationship between pMEK5 expression in CRC and clinicopathologic parameters, and the association of pMEK5 expression with CRC survival were analyzed respectively. RESULTS: pMEK5 expression was significantly higher in CRC tissues (185 out of 335, 55.2%) than in normal tissues (6 out of 80, 7.5%; P < 0.001). Western blotting demonstrated that pMEK5 expression was upregulated in 12 of 19 CRC tissues (62.1%) compared to the corresponding adjacent nontumor colorectal tissues. Overexpression of pMEK5 in CRC tissues was significantly correlated to the depth of invasion (P = 0.001), lymph node metastasis (P < 0.001), distant metastasis (P < 0.001) and high preoperative CEA level (P < 0.001). Consistently, the pMEK5 level in CRC tissues was increased following stage progression of the disease (P < 0.001). Analysis of the survival curves showed a significantly worse 5-year disease-free (P = 0.002) and 5-year overall survival rate (P < 0.001) for patients whose tumors overexpressed pMEK5. However, in multivariate analysis, pMEK5 was not an independent prognostic factor for CRC (DFS: P = 0.139; OS: P = 0.071). CONCLUSIONS: pMEK5 expression is correlated with the staging of CRC and its expression might be helpful to the TNM staging system of CRC.

Effects of Xiao Chengqi Formula on Slow Transit Constipation by Assessing Gut Microbiota and Metabolomics Analysis in vitro and in vivo.

The Xiao Chengqi (XCQ) formula is a newly constituted traditional Chinese medicine prescription in the treatment of intestinal motility deficiency and is effective in patients with slow transit constipation (STC). XCQ formula was reconstructed based on a "Chengqi" decoction. Astragali Radix, Angelicae Sinensis Radix, and cooked ground Salviae Miltiorrhizae Radix et Rhizoma were added to the prescription to enhance. An STC rat model was constructed and treated with the formula to understand the detailed mechanism by which XCQ promotes intestinal peristalsis. The effects of the XCQ formula on intestinal microflora and metabolic levels and the possible molecular mechanism of its regulation were explored using 16S rDNA sequencing, metabolomics sequencing, and tissue RNA sequencing. The results showed a significant decrease in the abundance of Roseburia spp. in the feces of STC rats, a significant decrease in the content of butyl aminobenzene (BAB) in feces, and an increase in the number of interstitial cells of Cajal (ICC) in the colon of STC rats. Furthermore, in vitro and in vivo experiments revealed that BAB could activate IL-21R on the ICC surface, upregulate the phosphorylation of the downstream molecules STAT3 and ERK, and inhibit loperamide-induced ICC apoptosis. Therefore, the XCQ formula can improve the defecation status of patients with STC by protecting ICC activity, promoting the colonization of Roseburia spp. to promote peristalsis, and increasing the BAB content after metabolism.

Single-Cell RNA Sequencing Reveals Heterogeneity in the Tumor Microenvironment between Young-Onset and Old-Onset Colorectal Cancer.

BACKGROUND: The incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. Compared with old-onset colorectal cancer (oCRC), yCRC has different clinical and molecular characteristics. However, the difference in the tumor microenvironment (TME) between yCRC and oCRC remains unclear. METHODS: Fourteen untreated CRC tumor samples were subjected to single-cell RNA sequencing analysis. RESULTS: B cells and naïve T cells are enriched in yCRC, while effector T cells and plasma cells are enriched in oCRC. Effector T cells of yCRC show decreased interferon-gamma response and proliferative activity; meanwhile, Treg cells in yCRC show stronger oxidative phosphorylation and TGF-ß signaling than that in oCRC. The down-regulated immune response of T cells in yCRC may be regulated by immune and malignant cells, as we observed a downregulation of antigen presentation and immune activations in B cells, dendritic cells, and macrophages. Finally, we identified malignant cells in yCRC and oCRC with high heterogeneity and revealed their interactions with immune cells in the TME. CONCLUSIONS: Our data reveal significant differences of TME between yCRC and oCRC, of which the TME of yCRC is more immunosuppressive than oCRC. Malignant cells play an essential role in the formation of the suppressive tumor immune microenvironment.

Comparison of seven screening methods in the diagnosis of bladder cancer.

BACKGROUND: We compared the validity (evaluated by sensitivity and specificity), reliability (evaluated by reproducibility) and yield (evaluated by predictive value, examining complexity and cost) of individual and combined tests for bladder tumour antigen stat (BTAstat), nuclear matrix protein 22 (NMP22), hyaluronic acid (HA), survivin, CD44v6, vascular endothelial growth factor (VEGF), and voided urine cytology (VUC) in detecting bladder cancer. And at the same time we evaluated the clinical value of these seven detecting methods in the diagnosis of bladder cancer. METHODS: The six markers and VUC were detected in the urine of cancer group (151 patients with bladder cancer) and two control groups (50 patients with benign urological diseases and 50 healthy controls). The sensitivity, specificity, predictive value, reproducibility, examining complexity and checking cost of each marker and combined markers were calculated. RESULTS: There was a significant difference between bladder cancer group and the two control groups. The sensitivity, specificity and positive predictive value were as follows: VUC (36.4%, 100.0%, 100%), BTAstat (76.8%, 87.0%, 89.9%), NMP22 (77.5%, 81.0%, 86.0%), HA (82.8%, 83.0%, 88.0%), survivin (70.2%, 85.0%, 87.6%), CD44v6 (50.3%, 79.0%, 78.4%), and VEGF (68.2%, 93.0%, 93.6%). The highest sensitivities were 91.4% for NMP22 + BTAstat and HA + NMP22, whereas the combined marker with the lowest sensitivity (62.3%) was VUC + CD44v6. The highest specificity was 93.0% for the combined use of VUC + VEGF and HA + CD44v6 had the lowest specificity (73.0%). The most convenient examining method was the detection for BTAstat, the lowest cost was the detection for HA, and the best reproducibility were the detection for BTAstat and VUC. CONCLUSIONS: All the markers have obvious clinical value in diagnosis of bladder cancer. The use of BTAstat + HA or NMP22 + BTAstat are better examining methods in terms of validity, reliability, and yield.