Gegen Qinlian decoction ameliorates TNBS-induced ulcerative colitis by regulating Th2/Th1 and Tregs/Th17 cells balance, inhibiting NLRP3 inflammasome activation and reshaping gut microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine Gegen Qinlian Decoction (GQD) has been clinically shown to be an effective treatment of ulcerative colitis (UC) in China. However, the underlying mechanism of GQD's anti-ulcerative colitis properties and its effect on gut microbiota still deserve further exploration. AIM OF THE STUDY: This study observed the regulatory effects of GQD on Th2/Th1 and Tregs/Th17 cells balance, the NOD-like receptor family pyrin domain containing 3 (NLRP3) infammasome and gut microbiota in TNBS-induced UC in BALB/c mice. MATERIALS AND METHODS: 61 main chemical compounds in the GQD were determined by UPLC-Q-TOF/MS. The UC BALB/c model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS), and GQD was orally administered at low and high dosages of 2.96 and 11.83 g/kg/day, respectively. The anti-inflammatory effects of GQD for ulcerative colitis were evaluated by survival rate, body weight, disease activity index (DAI) score, colonic weight and index, spleen index, hematoxylin-eosin (HE) staining and histopathological scores. Flow cytometry was used to detect the percentage of CD4, Th1, Th2, Th17 and Tregs cells. The levels of Th1-/Th2-/Th17-/Tregs-related inflammatory cytokines and additional proinflammatory cytokines (IL-1ß, IL-18) were detected by CBA, ELISA, and RT-PCR. The expressions of GATA3, T-bet, NLRP3, Caspase-1, IL-Iß, Occludin and Zonula occludens-1 (ZO-1) on colon tissues were detected by Western blot and RT-PCR. Transcriptome sequencing was performed using colon tissue and 16S rRNA gene sequencing was performed on intestinal contents. Fecal microbiota transplantation (FMT) was employed to assess the contribution of intestinal microbiota and its correlation with CD4 T cells and the NLRP3 inflammasome. RESULTS: GQD increased the survival rate of TNBS-induced UC in BALB/c mice, and significantly improved their body weight, DAI score, colonic weight and index, spleen index, and histological characteristics. The intestinal barrier dysfunction was repaired after GQD administration through promoting the expression of tight junction proteins (Occludin and ZO-1). GQD restored the balance of Th2/Th1 and Tregs/Th17 cells immune response of colitis mice, primarily inhibiting the increase in Th2/Th1 ratio and their transcription factor production (GATA3 and T-bet). Morever, GQD changed the secretion of Th1-/Th2-/Th17-/Tregs-related cytokines (IL-2, IL-12, IL-5, IL-13, IL-6, IL-10, and IL-17A) and reduced the expressions of IL-1ß, IL-18. Transcriptome results suggested that GQD could also remodel the immune inflammatory response of colitis by inhibiting NOD-like receptor signaling pathway, and Western blot, immunohistochemistry and RT-PCR further revealed that GQD exerted anti-inflammatory effects by inhibiting the NLRP3 inflammasome, such as down-regulating the expression of NLRP3, Caspase-1 and IL-1ß. More interestingly, GQD regulated gut microbiota dysbiosis, suppressed the overgrowth of conditional pathogenic gut bacteria like Helicobacter, Proteobacteria, and Mucispirillum, while the probiotic gut microbiota, such as Lactobacillus, Muribaculaceae, Ruminiclostridium_6, Akkermansia, and Ruminococcaceae_unclassified were increased. We further confirmed that GQD-treated gut microbiota was sufficient to relieve TNBS-induced colitis by FMT, involving the modulation of Th2/Th1 and Tregs/Th17 balance, inhibition of NLRP3 inflammasome activation, and enhancement of colonic barrier function. CONCLUSIONS: GQD might alleviate TNBS-induced UC via regulating Th2/Th1 and Tregs/Th17 cells Balance, inhibiting NLRP3 inflammasome and reshaping gut microbiota, which may provide a novel strategy for patients with colitis.

B-Mode ultrasound imaging in diagnosing carpal tunnel syndrome: an auxiliary diagnostic tool for hand surgeons.

Objective: The purpose of this article is to explore the effectiveness of B-Mode ultrasound as an auxiliary diagnostic tool for carpal tunnel syndrome (CTS). It aims to demonstrate the advantages of B-Mode ultrasound, including its non-invasive nature and its ability to provide real-time imaging, in localizing nerve compression and predicting postoperative outcomes. Methods: The study included 40 patients who were subjected to preoperative B-ultrasonography. The approach focused on evaluating the consistency of B-Mode ultrasound results with intraoperative findings. It also assessed the importance of employing standardized imaging techniques and emphasized the need for cooperation between hand surgeons and sonographers for accurate diagnosis. Results: B-Mode ultrasound findings in the study were consistent with intraoperative observations, indicating its reliability. Additionally, B-Mode ultrasound was able to identify other anatomical abnormalities within the carpal canal that may contribute to CTS symptoms, such as persistent median arteries, median nerve bifurcation, and space-occupying lesions like cysts and tumors. Conclusion: The article concludes that B-Mode ultrasound should be considered a valuable supplementary diagnostic tool for CTS, particularly in instances where clinical signs and electrophysiological studies do not offer clear results. However, it should not replace established diagnostic methods for CTS.

Panax notoginseng saponins normalises tumour blood vessels by inhibiting EphA2 gene expression to modulate the tumour microenvironment of breast cancer.

BACKGROUND: Panax notoginseng saponins (PNS), the main active component of Panax notoginseng, can promote vascular microcirculation. PNS exhibits antitumor effects in various cancers. However, the molecular basis of the relationship between PNS and tumor blood vessels remains unclear. PURPOSE: To study the relationship between PNS inhibiting the growth and metastasis of breast cancer and promoting the normalization of blood vessels. METHODS: We performed laser speckle imaging of tumor microvessels and observed the effects of PNS on tumor growth and metastasis of MMTV-PyMT (FVB) spontaneous breast cancer in a transgenic mouse model. Immunohistochemical staining of Ki67 and CD31 was performed for tumors, scanning electron microscopy was used to observe tumor vascular morphology, and flow cytometry was used to detect tumor tissue immune microenvironment (TME). RNA-seq analysis was performed using the main vessels of the tumor tissues of the mice. HUVECs were cultured in tumor supernatant in vitro to simulate tumor microenvironment and verify the sequencing differential key genes. RESULTS: After treatment with PNS, we observed that tumor growth was suppressed, the blood perfusion of the systemic tumor microvessels in the mice increased, and the number of lung metastases decreased. Moreover, the vascular density of the primary tumor increased, and the vascular epidermis was smoother and flatter. Moreover, the number of tumor-associated macrophages in the tumor microenvironment was reduced, and the expression levels of IL-6, IL-10, and TNF-α were reduced in the tumor tissues. PNS downregulated the expression of multiple genes associated with tumor angiogenesis, migration, and adhesion. In vitro tubule formation experiments revealed that PNS promoted the formation and connection of tumor blood vessels and normalized the vessel morphology primarily by inhibiting EphA2 expression. In addition, PNS inhibited the expression of tumor vascular marker proteins and vascular migration adhesion-related proteins in vivo. CONCLUSION: In this study, we found that PNS promoted the generation and connection of tumor vascular endothelial cells, revealing the key role of EphA2 in endothelial cell adhesion and tumor blood vessel morphology. PNS can inhibit the proliferation and metastasis of breast cancer by inhibiting EphA2, improving the immune microenvironment of breast cancer and promoting the normalization of tumor blood vessels.

The implication of gut microbiota in recovery from gastrointestinal surgery.

Recovery from gastrointestinal (GI) surgery is often interrupted by the unpredictable occurrence of postoperative complications, including infections, anastomotic leak, GI dysmotility, malabsorption, cancer development, and cancer recurrence, in which the implication of gut microbiota is beginning to emerge. Gut microbiota can be imbalanced before surgery due to the underlying disease and its treatment. The immediate preparations for GI surgery, including fasting, mechanical bowel cleaning, and antibiotic intervention, disrupt gut microbiota. Surgical removal of GI segments also perturbs gut microbiota due to GI tract reconstruction and epithelial barrier destruction. In return, the altered gut microbiota contributes to the occurrence of postoperative complications. Therefore, understanding how to balance the gut microbiota during the perioperative period is important for surgeons. We aim to overview the current knowledge to investigate the role of gut microbiota in recovery from GI surgery, focusing on the crosstalk between gut microbiota and host in the pathogenesis of postoperative complications. A comprehensive understanding of the postoperative response of the GI tract to the altered gut microbiota provides valuable cues for surgeons to preserve the beneficial functions and suppress the adverse effects of gut microbiota, which will help to enhance recovery from GI surgery.

Role of gut microbiota-derived signals in the regulation of gastrointestinal motility.

The gastrointestinal (GI) tract harbors trillions of commensal microbes, called the gut microbiota, which plays a significant role in the regulation of GI physiology, particularly GI motility. The GI tract expresses an array of receptors, such as toll-like receptors (TLRs), G-protein coupled receptors, aryl hydrocarbon receptor (AhR), and ligand-gated ion channels, that sense different gut microbiota-derived bioactive substances. Specifically, microbial cell wall components and metabolites, including lipopeptides, peptidoglycan, lipopolysaccharides (LPS), bile acids (BAs), short-chain fatty acids (SCFAs), and tryptophan metabolites, mediate the effect of gut microbiota on GI motility through their close interactions with the enteroendocrine system, enteric nervous system, intestinal smooth muscle, and immune system. In turn, GI motility affects the colonization within the gut microbiota. However, the mechanisms by which gut microbiota interacts with GI motility remain to be elucidated. Deciphering the underlying mechanisms is greatly important for the prevention or treatment of GI dysmotility, which is a complication associated with many GI diseases, such as irritable bowel syndrome (IBS) and constipation. In this perspective, we overview the current knowledge on the role of gut microbiota and its metabolites in the regulation of GI motility, highlighting the potential mechanisms, in an attempt to provide valuable clues for the development of gut microbiota-dependent therapy to improve GI motility.

Does application of indocyanine green fluorescence imaging enhance clinical outcomes in liver resection? A meta-analysis.

BACKGROUND: Indocyanine green fluorescence imaging technology has been widely used in liver resection. However, there has been a lack of strong evidence on whether application of indocyanine green fluorescence imaging enhances clinical outcomes in liver resection. This meta-analysis was performed to compare the latest clinical results of indocyanine green fluorescence imaging-guided hepatectomy (FIGH) and conventional hepatectomy (CH) in liver diseases. METHODS: Relevant clinical studies were retrieved from PubMed, Embase, Cochrane Library, Medline and the Web of Science databases until June 21, 2021. Stata14.0 software was adopted in meta-analysis, in which the pooled effect size was calculated by the random-effects model or the fixed-effects model. Meta-regression and subgroup analysis were used to explore sources of heterogeneity. The publication bias was ascertained by egger's test and begg's test. The trim and fill method was used to adjust the occurrence of publication bias. RESULTS: Overall twelve studies comprising 931 patients were included. Compared to the CH group, the FIGH group has lower complications (weighted mean difference [WMD] = 0.5238; 95% CI = 0.351-0.780; P = 0.001), shorter hospital stays (WMD = -1.857; 95% CI = -2.806--0.908; P = 0.000). Six of the studies indicated that no perioperative mortality occurred in either group. In overall analysis, there was no statistical difference in the estimated blood loss between the two groups (WMD = -42.509; 95% CI = -87.842 -2.825; P = 0.066), while in subgroup analysis of only literature from Japan or published between 2018 and 2019 years showed the consistent results above (WMD = 5.613; 95% CI = -45.101-56.328; P = 0.828. WMD = 5.582; 95% CI = -34.597-45.762; P = 0.785). No significant differences were found in operative time, blood transfusion rate, R0 resection, 1-year recurrence rate, 2-year-recurrence rate and the 1-year overall survival rate (P > 0.05). CONCLUSION: This meta-analysis showed that during the liver resection operation, application of indocyanine green fluorescence imaging is a feasible and safe method in the treatment of liver diseases, which enhances some clinical outcomes, such as lower complications and shorter hospital stays.

Robotic versus laparoscopic hepatectomy for malignancy: A systematic review and meta-analysis.

The aim of this study was to compare the clinical safety and efficacy of robotic hepatectomy (RH) versus conventional laparoscopic hepatectomy (LH) for malignancy using meta-analysis. A systematic literature search was performed using PubMed, EMBASE, Medline and the Cochrane Library databases up to September 2020 for studies, which limited to comparative articles of RH or LH for malignant tumors. Stata14.0 was performed in the meta-analysis. Six studies with a total of 1093 patients (345 RH and 748 LH) were eligible for inclusion. Operative time, tumor size, open procedure rate and the proportion of right hepatectomy were found to be significantly different between RH and LH in the pooled analysis (P < 0.05). Compared to LH, RH was associated with longer operative time, larger tumor size, lower open procedure rate and more common use for right hepatectomy. On the other hand, there was no difference in the operative time, estimated blood loss (EBL), blood transfusion rate, hospital stay, R0 resection rate, complications, resection margin, left lateral sectionectomy and left hepatectomy (P > 0.05). For malignant tumors that require hepatectomy, robotic approaches have demonstrated similar safety and feasibility to laparoscopy, with lower open procedure rate, were suitable for larger tumor size, and have a high right hepatectomy utilization rate. These results still need to be confirmed by multicenter, high-quality randomized controlled studies.