Meta-analysis on the efficacy of Traditional Chinese Medicine in enhancing surgical site wound healing post-colorectal surgery.

This meta-analysis aimed to evaluate the efficacy of Traditional Chinese Medicine (TCM) in enhancing surgical site wound healing following colorectal surgery. We systematically reviewed and analysed randomized controlled trials (RCTs) that investigated the outcomes of TCM interventions in postoperative wound management, adhering to the PRISMA guidelines. The primary outcome was the assessment of wound healing through the REEDA (redness, oedema, ecchymosis, discharge and approximation) scale at two different time points: the 10th day and 1-month post-surgery. Seven RCTs involving 1884 patients were included. The meta-analysis revealed a statistically significant improvement in wound healing in the TCM-treated groups compared to the control groups at both time intervals. On the 10th day post-surgery, the TCM groups exhibited a significant reduction in REEDA scale scores (I2 = 98%; random: SMD: -2.25, 95% CI: -3.52 to -0.98, p < 0.01). A similar trend was observed 1-month post-surgery, with the TCM groups showing a substantial decrease in REEDA scale scores (I2 = 98%; random: SMD: -3.39, 95% CI: -4.77 to -2.01, p < 0.01). Despite the promising results, the majority of the included studies were of suboptimal quality, indicating a need for further high-quality RCTs to substantiate the findings. The results suggest that TCM interventions can potentially enhance wound healing post-colorectal surgery, paving the way for further research in this area to validate the efficacy of TCM in postoperative management.

Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4/NLRP3-mediated pyroptosis.

OBJECTIVES: Ulcerative colitis (UC) is a common inflammatory bowel disorder. Gentiana scabra Bunge is a traditional medicinal plant that is used to treat a variety of diseases. Studies have shown that gentianine (GTN) from Gentiana scabra inhibits the development of inflammatory diseases. The purpose of this study was to investigate the effect and possible mechanism of action of GTN on UC in mice. METHODS: An animal model of UC was established using dextran sulfate sodium (DSS). Mice were administered intraperitoneally with GTN (12.5, 25, or 50 mg/kg/day) for seven days. Body weight and disease activity index (DAI) were monitored daily during GTN administration. Colon length, pathological changes, and myeloperoxidase (MPO) activity were measured following GTN administration. The signalling pathways regulated by GTN were analysed using machine learning. HT-29 cells were used to verify the effect and mechanism of action of GTN on UC in vitro. RESULTS: GTN suppressed weight loss, shortened colon length, alleviated colon injury, and reduced the DAI score and MPO activity of mice with UC in a dose-dependent manner. Further analysis showed that GTN inhibited the NOD-like receptor (NLR) signalling pathway. GTN markedly decreased the levels of NLR signalling pathway-related proteins. Moreover, GTN decreased the levels of pyroptosis-related proteins, IL-1ß and IL-18. The in vitro data were consistent with those of animal experiments. Furthermore, TLR4 and NLRP3 overexpression eliminated the protective effects of GTN in HT-29 cells. CONCLUSION: Gentianine alleviated DSS-induced UC by inhibiting TLR4/NLRP3-mediated pyroptosis.

Identification of Comprehensive Biomarkers in Patients With Mismatch Repair-Deficient Colon Adenocarcinoma Based on Parallel Multiomics.

Immunocheckpoint inhibitors have shown impressive efficacy in patients with colon cancer and other types of solid tumor that are mismatch repair-deficient (dMMR). Currently, PCR-capillary electrophoresis is one of the mainstream detection methods for dMMR, but its accuracy is still limited by germline mismatch repair (MMR) mutations, the functional redundancy of the MMR system, and abnormal methylation of MutL Homolog 1 promoter. Therefore, this study aimed to develop new biomarkers for dMMR based on artificial intelligence (AI) and pathologic images, which may help to improve the detection accuracy. To screen for the differential expression genes (DEGs) in dMMR patients and validate their diagnostic and prognostic efficiency, we used the expression profile data from the Cancer Genome Atlas (TCGA). The results showed that the expression of Immunoglobulin Lambda Joining 3 in dMMR patients was significantly downregulated and negatively correlated with the prognosis. Meanwhile, our diagnostic models based on pathologic image features showed good performance with area under the curves (AUCs) of 0.73, 0.86, and 0.81 in the training, test, and external validation sets (Jiangsu Traditional Chinese Medicine Hospital cohort). Based on gene expression and pathologic characteristics, we developed an effective prognosis model for dMMR patients through multiple Cox regression analysis (with AUC values of 0.88, 0.89, and 0.88 at 1-, 3-, and 5-year intervals, respectively). In conclusion, our results showed that Immunoglobulin Lambda Joining 3 and nucleus shape-related parameters (such as nuclear texture, nuclear eccentricity, nuclear size, and nuclear pixel intensity) were independent diagnostic and prognostic factors, suggesting that they could be used as new biomarkers for dMMR patients.

Ferulic acid relieved ulcerative colitis by inhibiting the TXNIP/NLRP3 pathway in rats.

Ulcerative colitis (UC) is a disorder of the bowel that is characterized by a chronic inflammatory response. The traditional Chinese herbal medicine ferulic acid (FA) is known for its antioxidant, antiapoptotic, and antiinflammatory properties. However, its role in UC is still unclear. Thus, the current study was conducted to investigate the role of FA in UC. Rats were treated with 2,4,6-triabrobenzene sulfonic acid to induce UC and subjected to FA. Human intestinal microvascular endothelial cells (HIMECs) were treated with tumor necrosis factor-α (TNF-α) and pretreated with FA. Pathological changes in colonic tissues were visualized via hematoxylin-eosin staining. Enzyme linked immunosorbent assay was conducted to detect interleukin (IL)-6, IL-12, and IL-1ß levels. Cell morphology was visualized by using a microscope, and viability was detected by using MTT. The percentage of apoptosis was detected via flow cytometry. Western blot analysis was performed to detect the expression of the apoptosis-related proteins thioredoxin-interacting protein (TXNIP) and NOD-like receptor pyrin domain-containing 3 (NLRP3). In vivo FA administration alleviated intestinal injury in UC rats and inhibited inflammatory factor levels (IL-6, IL-12, and IL-1ß), apoptosis-related protein expression (caspase-1 and caspase-3) and the TXNIP/NLRP3 signaling pathway. In vitro, TNF-α treatment reduced HIMEC viability, increased cell apoptosis and inflammatory factor levels and activated the TXNIP/NLRP3 signaling pathway. However, FA treatment restored the viability of HIMECs, reduced TNF-α-induced cell apoptosis and inflammation and inhibited the TXNIP/NLRP3 signaling pathway. Furthermore, with increasing FA concentration, the effects were stronger. In summary, FA inhibits the inflammatory injury of endothelial cells in ulcerative colitis or alleviates TNF-α-induced HIMEC injury by inhibiting the TXNIP/NLRP3 signaling pathway.

[Effect of warm-needle moxibustion intervention on immune function and intestinal flora in patients after colorectal cancer radical operation].

OBJECTIVE: To explore the effect of warm-needle moxibustion (WNM) on the levels of T cell subgroups and serum inflammatory factors, intestinal microecological balance and postoperative adverse reactions in patients with colorectal cancer. METHODS: Eighty-four patients who underwent elective radical resection of colorectal cancer were randomly and equally divided into control (medication) group (23 men and 19 women) and WNM group (24 men and 18 women). Patients of the control group received conventional medication treatment (such as postoperative anti-infection and fluid supplementation), and those of the WNM group received conventional medication plus WNM stimulation (the acupuncture needle handle warmed by ignited moxa stick) of bilateral Zusanli(ST36), Sanyinjiao(SP6), Yinlingquan(SP9), Shangjuxu(ST37), and Zhaohai(KI6). The acupuncture needles were retained for 45 minutes every time, starting on the first day after surgery, once a day for 15 days. The number of T cell subsets (CD3+, CD4+, CD8+) positive cells was counted under fluorescence microscope, and the contents of serum tumor necrosis factor α(TNF-α) and interleukin-6 (IL-6) were detected by using ELISA, and the level of C-reactive protein (CRP) was detected by using immunoturbidimetry. The levels (logarithm of colony-forming units per gram of wet fecal weight) of Bifidobacterium, Lactobacillus, Escherichia coli and Enterococcus were determined. The adverse reactions (leukocyte decline, nausea and vomiting, peripheral phlebitis, cold stimulation sensitivity) were recorded after surgery. RESULTS: Before treatment, there were no significant differences between the two groups in the number of T cell subgroups, TNF-α and IL-6 contents, and intestinal flora numbers (P>0.05). After the treatment, self-comparison showed that the numbers of CD3+ and CD4+ positive cells, the ratio of CD4+/CD8+ and the intestinal Bifidobacterium and Lactobacillus levels in the WNM group were significantly increased (P<0.05), whereas the number of CD8+positive cells, intestinal Escherichia coli and Enterococcus levels in the WNM group, and the levels of TNF-α, IL-6 and CRP in both groups were obviously decreased in comparison with their own pretreatment (P<0.05), but no significant changes were found in the levels of CD3+ and CD4+ positive cells, CD4+/CD8+ and intestinal Bifidobacterium, Lactobacillus, Escherichia coli and Enterococcus in the control group (P>0.05). Comparison between two groups displayed that after the treatment, the numbers of CD3+ and CD4+ positive cells, the ratio of CD4+/CD8+, as well as the levels of Bifidobacterium and Lactobacillus were significantly higher in the WNM group than in the control group (P<0.05), whereas the number of CD8+ positive cells， TNF-a, IL-6 and CRP, and the levels of Escherichia coli and Enterococcus were obviously lower in the WNM group than in the control group (P<0.05). The incidence of adverse reactions including leukopenia, nausea and vomiting, peripheral phlebitis, and sensitivity to cold stimulation in the WNM group were markedly lower than those of the control group (P<0.05). CONCLUSION: WNM intervention can significantly improve the immune function, reduce the level of inflammatory factors, regulate the level of beneficial intestinal flora, and also reduce the incidence of postoperative adverse reactions in patients experiencing radical resection of colorectal cancer.

Inhibition of autophagy of Cajal mesenchymal cells by gavage of tong bian decoction based on the rat model of chronic transit constipation.

The objective of this research was to study the effect of tong bian decoction on colon transport function of interstitial cells of Cajal (ICC) in chronic transit constipation (CTC) and the inhibition of autophagy of ICC, so as to achieve the free movement of the bowels. In this research, the experimental rats were divided into normal group (NG) and model group (MG) by random method, and the rat model of CTC was constructed by subdivision circulatory increasing operation gavage method of rhubarb. After the successful establishment of the model, the rats were divided into normal group, MG, tong bian decoction gavage group, mosapride group and normal recovery group. Then, rats in the NG and the MG were killed at the same time, and rats in the tong bian decoction gavage group, mosapride group and normal recovery group were killed at the same time. In this study, the transport function of colon of rats in each group was detected by activated carbon method, and the number of fecal residues in the colon was observed. The mRNA expression of c-kit gene in intestinal tissue of rat was detected by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the changes of ICC in rats treated with different drugs were detected by immunohistochemical method. The results revealed that in the tong bian decoction gavage group, the water content in the feces of rats was remarkably increased (P < 0.05), the amount of residual feces in the colon was remarkably reduced (P < 0.01), the percentage of carbon powder propulsion in small intestine was remarkably increased (P < 0.01), the staining area of ICC positive cells in colon tissue was remarkably increased (P < 0.05), and the expression of c-kit mRNA was remarkably increased (P < 0.01). It can be concluded that the tong bian decoction could effectively enhance the colon transport function in the rat model of CTC. This laxative mechanism promotes the regeneration and repair ability of ICC by inhibiting the autophagy of ICC, and provides power for the large intestine, so as to achieve the free movement of the bowels. Therefore, the results of this study have certain guiding meaning for the treatment of CTC with traditional Chinese medicine.

Garlic intake and the risk of colorectal cancer: A meta-analysis.

This was a meta-analysis of epidemiological articles that aimed to estimate the association of garlic intake with the risk of colorectal cancer (CRC).Electronic databases, including the Cochrane Database of Systematic Reviews, PubMed, and EMBASE, were systemically searched from inception to May 2019 to identify related articles. In addition, a random model was used to pool the included evidence based on heterogeneity. Additionally, subgroup analyses were carried out to examine the differences between different groups. The stability of our findings was tested through sensitivity analyses. Publication bias was also assessed by Egger and Begg tests. Moreover, all enrolled studies were ordered according to the publication year for a cumulative meta-analysis.A total of 11 studies (involving 12,558 cases) were included in the current meta-analysis. Our integrated relative risk (RR) of CRC was 0.80 (95% confidence interval [CI], 0.69-0.91) for the highest versus the lowest garlic consumption categories (RR: 0.71 [95% CI, 0.60-0.84] for controls and RR: 0.99 [95% CI, 0.80-1.23] for cohorts). There was significant heterogeneity across all enrolled studies (I = 68.3%, P < .01). The sensitivity analysis revealed no notable alterations of the integrated results. According to the funnel plot regarding garlic intake and the risk of CRC, together with the Egger test (P = .1) and Begg test (P = .064) results, there was no notable evidence of publication bias. The cumulative meta-analysis suggested that the 95% CIs became narrower with the increase in sample size.Based on the existing evidence, garlic intake could reduce the risk of CRC.

[Effect on Postoperative Complications of Mixed Hemorrhoids Treated with Electroacupuncture at Chengshan(BL 57), Dachangshu(BL 25)and Erbai(EX-UE 2)].

OBJECTIVE: To evaluate the effect on postoperative complications of mixed hemorrhoids treated with electroacupuncture(EA) at Chengshan(BL 57)，Dachangshu(BL 25)and Erbai(EX-UE 2). METHODS: A total of 60 patients with mixed hemorrhoids were randomly divided into control and EA groups，30 cases in each group. In addition to basic treatment, EA was applied at BL 57, BL 25 and EX-UE 2 for 30 min (2 Hz/15 Hz，0.5－2 mA) each day for 3 days after surgery in the EA group, while the control group received basic treatment after surgery. Postoperative complications after treatment were evaluated each day. RESULTS: Following surgery, anal pain, anal pendant expansion and hematochezia were observed in both the EA group and control group. On the first day after surgery, symptom improvement was not statistically significantly different between the two groups (P>0.05)．On the 2nd and 3rd days after surgery, anal pain, anal pendant expansion and hematochezia were markedly improved in the EA group compared with those in the control group (P<0.05). CONCLUSIONS: Electroacupuncture can reduce anal pain, anal pendant expansion and hematochezia after surgery in patients with mixed hemorrhoids.

Aqueous Extracts of Herba Cistanche Promoted Intestinal Motility in Loperamide-Induced Constipation Rats by Ameliorating the Interstitial Cells of Cajal.

Traditional Chinese medicine was reported to have good effects in treating functional constipation. This work attempted to prove the effects of aqueous extracts of Herba Cistanche (AEHC) on STC treatment and to determine the possible mechanisms by a loperamide-induced slow transit constipation (STC) model. HPLC was performed for identification and confirmation of the bioactive components in the AEHC. It was found that AEHC attenuated STC responses based on increased fecal quantity, moisture content, and intestinal transit rate, as well as serum levels of GAS, MTL, SS, and CGRP. The protein and mRNA levels of c-kit, a labeling of interstitial cells of Cajal (ICC), also increased. Meanwhile, only the protein level of SCF, a ligand of c-kit, increased. The analysis of our data suggested that AEHC could obviously improve the function of ICC via a signaling pathway involving PI3K, SCF, and c-kit and enhance colonic motility indices such as GAS, MTL, SS, and CGRP. It is interesting to note that AEHC appeared to be effective on constipation, so further experiments are necessary to clarify the exact mechanisms involved.

Icaritin induces cell death in activated hepatic stellate cells through mitochondrial activated apoptosis and ameliorates the development of liver fibrosis in rats.

AIM OF THE STUDY: Icaritin is an active ingredient extracted from the plant Herba Epimedium Sagittatum (Sieb. et Zucc.) Maxim. The purpose of this study is to investigate the effects and mechanisms of icaritin-induced cell death in activated hepatic stellate cells (HSCs) and ameliorating the development of liver fibrosis in rats. MATERIALS AND METHODS: : In vitro, icaritin-induced cell death rates in HSC-T6 (rat) and LX-2 (human) HSC lines as well as normal hepatocyte cell lines HL-7702 (L02) and WRL-68 were assayed by MTT method, and the apoptotic ratios were detected by both flow cytometry and the Annexin-V-FITC Apoptosis Detection Kit. A Whole Rat Genome Microarray Kit was used to identify expression of interest genes through fold-change screening. In vivo study, experimental liver fibrosis models were built by carbon tetrachloride (CCl(4)) or common bile duct ligation (CBDL) in Wistar rats. Icaritin (1mg/kg/day, three days a week) was administered by gastric gavage for four weeks (n=6 per group). At the end of the study, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) as well as the contents of hydroxyproline and collagen I in liver tissues were measured. Histopathological changes and the distribution of activated HSCs were observed in the liver tissues using hematoxyline-eosin (HE) staining and immunohistochemical staining for α-smooth muscle actin (α-SMA). RESULTS: Icaritin induced apoptosis in HSC-T6 and LX-2 in a concentration- and time-dependent manner with little toxicity to normal hepatocyte cell lines. The IC(50) of icaritin in HSC-T6 was 12.83 µM at 48 h. Apoptotic ratio of HSC-T6 treated with 24 µM icaritin was 20.19%, and the G2 phase of the cell cycle did not occur (P<0.05). Gene analysis showed that icaritin up-regulated Bak-1, Bmf and Bax expression while significantly down-regulated Bcl-2 expression (vs. control group, P<0.01). These results suggested that mitochondrial pathway played an important role in icaritin-induced apoptosis in activated HSCs. In vivo results showed that icaritin reduced the number of activated HSCs, and brought the elevated levels of AST, ALT, hydroxyproline and collagen I to normal or near normal values (vs. model group, P<0.05). CONCLUSIONS: Icaritin can induce cell death in activated HSCs through mitochondria-mediated apoptosis, ameliorate the progression of hepatic fibrosis in rats, and could be a promising drug for treating liver fibrosis.

[Clinical observation on the effect of acupuncture-assisted anesthesia for 40 cases of mixed hemorrhoids surgery].

OBJECTIVE: To observe the efficacy of comined administration of acupuncture and anesthetics for mixed hemorrhoids surgery and its postoperative complications. METHODS: A total of 40 cases of mixed hemorrhoid patients were randomized into acupuncture-assisted anesthesia (AAA) group and narcotic drug group (control), with 20 cases in each. For patients of AAA group, electroacupuncture (EA, 2 Hz/100 Hz, 9 mA) was applied to Changqiang (GV 1) and Yaoshu (GV 2) for 20 min, and 1% lidocaine (5 mL) was injected into GV 1. For patients of control group, 20 mL and 10 mL of 1% lidocaine were injected into GV 2 and GV 1, separately. The patients' pain response, anus muscular relaxion state, and postoperative complications were observed to evaluate their clinical efficacy. RESULTS: Of the 20 cases in AAA and control groups, 16 and 18 cases had a striking analgesic effect, 4 and 2 were effective, respectively. No significant difference was found between two groups in the analgesic efficacy for surgery (P>0.05). Postoperative urinary retention, pain severity I and II and the cases with intoxic response in AAA and control groups were 1 and 8, 16 and 6, 4 and 14, and 1 and 9, separately. The effects of AAA group were significantly superior to those of control group in lessening urinary retention and toxication, and in inducing analgesia (P<0.05). CONCLUSION: Acupuncture combined with narcotic drugs is superior to simple anesthetics for mixed hemorrhoids surgery in reducing postoperative complications.