Quercetin and its derivatives for wound healing in rats/mice: Evidence from animal studies and insight into molecular mechanisms.

Aimed to clarify the effect of quercetin and its derivatives on wound healing in animal experiments. PubMed, Embase, Science Direct, Web of Science, SinoMed, Vip Journal Integration Platform, China National Knowledge Infrastructure and WanFang databases were searched for animal experiments investigating the effect of quercetin and its derivatives on wound healing to April 2023. The Review Manager 5.4 software was used to conduct meta-analysis. Eighteen studies were enrolled in this article. According to the SYRCLE's RoB tool assessment, these studies exposed relatively low methodological quality. It was shown that animals with cutaneous wound receiving quercetin had faster wound healing in wound closure (%) than the control group. Moreover, the difference in efficacy gradually emerged after third day (WMD = 7.13 [5.52, 8.74]), with a peak reached on the tenth day after wounding (WMD = 19.78 [17.82, 21.74]). Subgroup analysis revealed that quercetin for wound closure (%) was independent of the types of rats and mice, wound area and with or without diabetes. Clear conclusion was also shown regarding the external application of quercetin for wound healing (WMD = 17.77 [11.11, 24.43]). A significant reduction in the distribution of inflammatory cells occurred in the quercetin group. Quercetin could increase blood vessel density (WMD = 1.85 [0.68, -3.02]), fibroblast distribution and collagen fraction. Biochemical indicators, including IL-1ß, IL-10, TNF-α, TGF-ß, vascular endothelial growth factor (VEGF), hydroxyproline and alpha-smooth muscle actin (α-SMA), had the consistent results. Quercetin and its derivatives could promote the recovery of cutaneous wound in animals, through inhibiting inflammatory response and accelerating angiogenesis, proliferation of fibroblast and collagen deposition.

Tumor necrosis factor suppresses interleukin 10 in peripheral B cells via upregulating Bcl2-like protein 12 in patients with inflammatory bowel disease.

The pathogenesis of the immune regulation dysfunction is unclear. Bcl2-like protein 12 (Bcl2L12) has immune suppression function. This study tests a hypothesis that tumor necrosis factor (TNF) increases Bcl2L12 to suppress the expression of interleukin (IL) 10 in peripheral B cells of patients with inflammatory bowel disease (IBD). In this study, peripheral blood samples were collected from IBD patients and healthy controls. B cells were isolated from the blood samples. The expression of IL-10 and Bcl2L12 in B cells was analyzed by quantitative reverse transcription polymerase chain reaction and Western blotting. We observed that the expression of Bcl2L12 in the peripheral B cells was higher in IBD patients than that in healthy controls. The IL-10 levels in B cells were negatively correlated with the expression of Bcl2L12. Exposure of B cells to TNF in the culture enhanced the expression of Bcl2L12. The Bcl2L12 mediated the effects of TNF on suppression of IL-10 in B cells. In conclusion, Bcl2L12 mediates the effects of TNF to suppress the expression of IL-10 in B cells. The data suggest that Bcl2L12 may be a therapeutic target for the treatment of IBD.

Brucine D restrains colorectal cancer tumorigenesis and autophagy by downregulating circ_0068464.

Bruceine D (BD) from Brucea javanica (L) exerts an antitumor effect in several human cancers. At present, it has not been reported whether BD inhibits the malignancy of colorectal cancer (CRC) cells. Therefore, investigating the role and regulatory mechanisms of BD in CRC is the main thrust of this study. Effect of BD on CRC cell viability, proliferation, apoptosis, invasion, and autophagy was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, 5-ethynyl-2'-deoxyuridine, flow cytometry, transwell invasion, and western blotting assays. Expression changes of has_circ_0068464 (circ_0068464) were detected using real time quantitative polymerase chain reaction. The molecular mechanisms related to circ_0068464 were predicted through online prediction websites Starbase 2.0, circinteractome, and CircBank and validated using dual-luciferase reporter and RNA pull-down assays. The tumorigenic ability of BD and circ_0068464 on CRC was confirmed by xenograft experiments. The results showed that BD lessened CRC cell proliferation, invasion, autophagy, and prompted cell apoptosis. Circ_0068464 was overexpressed in CRC samples and cells. BD led to a significant reduction in circ_0068464 levels in cells of this carcinoma, but circ_0068464 overexpression partially rescued these effects urged by BD. Also, the combination of BD and circ_0068464 silencing decreased xenograft tumor growth compared to BD alone. Importantly, circ_0068464 could regulate ATG5 expression by functioning as a miR-520h molecular sponge. In conclusion, BD might suppress CRC growth by inhibiting the circ_0068464/miR-520h/ATG5 axis, providing a new perspective for the molecular pathogenesis of CRC and preliminarily indicating that BD may be a promising drug for CRC treatment.

Ferroptosis-Mediated Immune Microenvironment and Therapeutic Response in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by dysregulated immune responses in the gastrointestinal tract. One intriguing aspect of IBD is the potential involvement of ferroptosis, but the mechanism remains incompletely understood. In this study, 27 ferroptosis-related genes (FRGs) were identified differentially expressed between IBD and non-IBD control samples. We used CIBERSORT to compare alterations in the mucosal immune microenvironment between the above two group samples, and found that M1 macrophages and neutrophil infiltration increased in IBD. Two clusters based on consensus clustering of 27 FRGs led to significant changes in the abundance of CD4 memory resting T cells, M2 macrophages, and resting mast cells. Subsequently, 23 hub genes were identified, which could distinguish IBD samples into two distinct clusters with noticeable differences in immune therapy response. Furthermore, scRNA sequencing data based on these 23 hub genes uncovered the highest ferroptosis scores in CD8+ T effector memory (Tem) cells, and their expression underwent significant changes along the differentiation trajectory of CD8+ Tem cells. The random forest model identified eight decisive genes, out of which ferroptosis-related hub genes (SEMA3E, SLC46A1, AC092652.1, DACT2, IL17C, and KRTAP5.2) were confirmed by RT-qPCR in the IBD mouse model. This study reveals ferroptosis-mediated immune microenvironment in IBD and provides multiple potential targets for IBD treatment.

Prognostic value of lymphocyte-to-monocyte ratio in gastric cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: Emerging evidence suggests a correlation between the lymphocyte-monocyte ratio (LMR) and the prognosis in patients with gastric cancer (GC) undergoing immune checkpoint inhibitor (ICI) therapy. Nevertheless, the existing findings remain contentious. Methods: A comprehensive search of literature was conducted in databases including PubMed, Embase, Web of Science, and the Cochrane Library, spanning from the inception of each database to August 30, 2023 to collect studies exploring the interplay between LMR and clinical outcomes. Eligible studies were selected following predefined inclusion and exclusion criteria. Primary outcomes encompassed progression-free survival (PFS) and overall survival (OS), which were estimated using hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results: Our analysis incorporated eight cohort studies, involving 815 patients. Aggregate data revealed associations between an elevated LMR at baseline and prolonged PFS (HR=0.58; 95% CI: 0.47-0.71, p<0.00001) and improved OS (HR=0.51, 95% CI: 0.33-0.79; p=0.003). Furthermore, LMR exhibited a favorable association with PFS after treatment (HR=0.48; 95% CI: 0.29-0.79; p= 0.004), while such a correlation was not evident in the OS analysis. Importantly, a high level of LMR was associated with prolonged PFS across varying sample sizes, follow-up duration, treatment combinations, line of therapy, and cut-off values. Conclusion: A high pre-treatment LMR is associated with improved OS and PFS in GC patients treated with ICIs. LMR emerges as a potent biomarker for prognostic assessment in these patients, offering valuable insights for informed treatment decisions within the domain of GC immunotherapy. Systematic review registration: PROSPERO, identifier CRD42021228512.

Traditional Chinese Medicine in the treatment of hemorrhoids-a review of preparations used and their mechanism of action.

Hemorrhoids are a proctological disease primarily characterized by bleeding, prolapse, edema, and pain, severely affecting the quality of life. Surgery is an effective treatment for hemorrhoids, but the cost is relatively high, and complications such as difficulty in defecation, persistent pain, and heavy bleeding may occur postoperatively. Traditional Chinese Medicine (TCM) has a distinctive advantage in alleviating the clinical symptoms of hemorrhoid patients, reducing pain, and improving the quality of life. However, there are few summary literature about the mechanism of TCM in the prevention and treatment of hemorrhoids. Based on the etiology of hemorrhoids in both traditional Chinese and Western medicine, this paper reviews the recent research on the mechanism of TCM in the treatment of hemorrhoids, hoping to provide a basis for the better application of TCM in clinical and experimental research.

Acupuncture and Moxibustion in the Treatment of Adult Diarrhea Irritable Bowel Syndrome: A Network Meta-analysis.

Objective: This study was aimed at comparing the clinical efficacy of acupuncture and moxibustion on irritable bowel syndrome complicated with diarrhea (IBS-D) in adults and providing guidance for clinical treatment. Methods: PubMed, The Cochrane Library, Embase, CBM, CNKI, and VIP and Wanfang databases were searched to obtain clinical randomized controlled trials (RCTs) on acupuncture and moxibustion in the treatment of IBS-D published from establishment of the database to August 5, 2021. Relevant data were extracted to assess the risk of bias in the included studies, and statistical software Stata 16.0 was used for meta-analysis. Results: Twenty-one studies were eventually included in the network meta-analysis (NMA), including 1626 patients with IBS-D and 8 therapeutic measures. NMA showed that acupuncture [OR = 0.35, 95%CI (0.25, 0.49), P < 0.05], warming needle moxibustion [OR = 6.34, 95%CI (2.83, 14.21), P < 0.05], acupuncture+sandwiched moxibustion [OR = 12.83, 95%CI (4.49, 36.64), P < 0.05], acupuncture+heat-sensitive moxibustion [OR = 9.86, 95%CI (1.77, 55.00), P < 0.05] were more effective than pinaverium bromide in the treatment of IBS-D. Cumulative ranking probability (SUCRA) showed that the comprehensive efficacy of acupuncture and moxibustion (86.8%) and quality of life (QOL) (70.4%) was the best, while the comprehensive efficacy of pinaverium bromide (2.1%) and QOL (16.3%) was the worst. GV20, GV29, ST 25, ST37, ST36, SP6, LR3, and CV12 were used frequently. Conclusion: Acupuncture+sandwiched moxibustion has the best effect on improving the efficacy and QOL of IBS-D patients. Limited by the number and quality of studies, we still need a large sample, multicenter, and high-quality clinical trials to confirm our findings.

Three Acupuncture Methods for Postoperative Pain in Mixed Hemorrhoids: A Systematic Review and Network Meta-Analysis.

Background: Mixed hemorrhoids are a common anorectal disorder, surgery is the most effective means of eradicating hemorrhoids, and pain is the most common postoperative complication of mixed hemorrhoids. Objective: To compare the clinical efficacy of auricular plaster, acupoint application, and acupoint catgut embedding for treating postoperative pain in mixed hemorrhoids. Method: PubMed, Embase, The Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and CBM databases were searched for randomized controlled trials (RCTs) of three acupuncture-related therapies for postoperative pain in mixed hemorrhoids from the time of database creation to October 2021. After screening the literature, extracting information, and evaluating the risk of bias of included studies, statistical analysis was performed using RevMan 5.3 and Stata 15.0. Result: Forty-seven RCTs with a total of 5121 patients were included. Network meta-analysis (NMA) showed that auricular plaster (OR = 5.90, 95% CI = (2.02, 17.21)) and acupoint catgut embedding therapy (OR = 5.55, 95% CI = (1.01, 30.40)) were more effective than analgesics in the treatment of postoperative pain in mixed hemorrhoids. The cumulative ranking probability (SUCRA) showed that acupoint application (73.6%) had the best overall efficacy and the rest were auricular plaster (68.7%), acupoint catgut embedding therapy (64.6%), auricular plaster combined with acupoint application (63.4%), and pain medication (8.9%) in that order. Secondly, auricular plaster (OR = -0.93, 95% CI = (-1.66, -0.20)), acupoint catgut embedding (OR = -0.8, 95% CI = (-1.50, -0.10)), and acupoint application (OR = -1.4, 95% CI = (-2.50, -0.31)) all led to a significant decrease in pain scores and were all more effective than analgesics. As ranked by SUCRA, the results showed that the efficacy of acupoint application (73.5%) was optimal and the rest were auricular plaster (56.1%), acupoint catgut embedding (50.2%), and pain medication (15.3%) in that order. In terms of pain degree, acupoint application (OR = 3.83, 95% CI = (1.25, 11.74)) was significantly better than pain medication. Conclusion: Acupoint application can improve the overall efficiency, reduce pain scores, and relieve the degree of postoperative pain in mixed hemorrhoids.

In-situ synthesis of polypyrrole/silver for fabricating alginate fabrics with high conductivity, UV resistance and hydrophobicity.

In this research, the polypyrrole/silver (PPy/Ag) composite was first in-situ prepared on alginate fabrics by chemical oxidative polymerization of pyrrole (Py) monomer using silver nitrate as oxidant and sodium dodecyl sulfate (SDS) as the dopant. The effects of mole ratio of Py to silver nitrate, reaction time and dopant concentration on the preparation of PPy/Ag composite were optimized. It was found the optimal molar ratio of Py to silver nitrate was 1:1.5 with 0.02 M SDS under the reaction time of 10 h. Then, the microstructure and properties of resultant PPy/Ag composite were analyzed by scanning electron microscope (SEM), Fourier infrared spectrometer (FT-IR), X-ray diffraction spectroscopy (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy and the thermogravimetry analysis (TGA), respectively. Finally, the influences of PPy/Ag coating on the performance of alginate fabrics including electrical conductivity, hydrophilicity, antistatic property and anti-ultraviolet capability were determined. It was found that the electrical conductivity of alginate fabric could be intensively increased after PPy/Ag coating. Meantime, the anti-ultraviolet capability and hydrophobicity could be largely improved by PPy/Ag coating especially under high Py dosage. This paper introduced a simple method for preparing PPy/Ag composite direct on alginate fabric to make it a good functional substrate which could be applied in many fields.

Feedback activation of STAT3 limits the response to PI3K/AKT/mTOR inhibitors in PTEN-deficient cancer cells.

The PI3K/AKT/mTOR signaling pathway is constitutively active in PTEN-deficient cancer cells, and its targeted inhibition has significant anti-tumor effects. However, the efficacy of targeted therapies is often limited due to drug resistance. The relevant signaling pathways in PTEN-deficient cancer cells treated with the PI3K/mTOR inhibitor BEZ235 were screened using a phosphokinase array, and further validated following treatment with multiple PI3K/AKT/mTOR inhibitors or AKT knockdown. The correlation between PTEN expression levels and STAT3 kinase phosphorylation in the tissue microarrays of gastric cancer patients was analyzed by immunohistochemistry. Cell proliferation and clonogenic assays were performed on the suitably treated PTEN-deficient cancer cells. Cytokine arrays, small molecule inhibition and knockdown assays were performed to identify related factors. PTEN-deficient tumor xenografts were established in nude mice that were treated with PI3K/AKT/mTOR and/or STAT3 inhibitors. PTEN deficiency was positively correlated with low STAT3 activity. PI3K/mTOR inhibitors increased the expression and secretion of macrophage migration inhibitory factor (MIF) and activated the JAK1/STAT3 signaling pathway. Both cancer cells and in vivo tumor xenografts showed that the combined inhibition of PI3K/AKT/mTOR and STAT3 activity enhanced the inhibitory effect of BEZ235 on the proliferation of PTEN-deficient cancer cells. Our findings provide a scientific basis for a novel treatment strategy in cancer patients with PTEN deficiency.

Effects of local injection and intravenous injection of allogeneic bone marrow mesenchymal stem cells on the structure and function of damaged anal sphincter in rats.

Anal sphincter injury leads to damage to the anal structure and functions and has been identified as a major risk factor for fecal incontinence. Bone marrow mesenchymal stem cells (BMSCs) with capacities of multidifferentiation, paracrine, and low immunogenicity have been widely used in tissue repair and regeneration. The primary objective of this research was to compare the effects of different injection therapies of BMSCs on the injured anal sphincters. Ninety-six Sprague-Dawley female rats were randomly divided into four groups (n = 24 each): intravenous injection, local injection, sham operation, and normal control. For the first three groups, 25% removal of the anal sphincter complex was performed and 0.3-ml phosphate-buffered saline (PBS) (containing 107 green fluorescent protein-labeled allogeneic BMSCs) was given accordingly to the treatment group 24 h after operation for 7 consecutive days. The sham operation group was injected with 0.3-ml PBS only. All cases had undergone evaluation in the 1st, 7th, 14th, and 28th postoperative days. The rats were sacrificed on the 28th postoperative day, and the anal sphincters were dissected to be analyzed by morphological examination. At 14 days postoperatively, local injection of BMSC significantly improved the peak contraction pressure, electromyography amplitude, and frequency of the injured anal sphincter compared with tail vein, but there was no significant difference in resting pressure until 28 days after sphincterectomy. Masson staining results confirmed that the local injection group had significantly more new muscles on the wound. BMSC could remarkably improve peak contraction pressure, electromyography amplitude, and muscle fibers on the wound, and local injection is superior to intravenous injection.

Effects of the pestle needle therapy, a type of acupoint stimulation, on post-hemorrhoidectomy pain: A randomized controlled trial.

BACKGROUND: Hemorrhoids are one of the most common conditions that lead to surgery, and until now surgical hemorrhoidectomy has been the major effective treatment. Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation. OBJECTIVE: This study evaluates the clinical efficacy of the pestle needle therapy, an acupoint stimulation method, for relief of post-hemorrhoidectomy pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This was a single-center, patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery. Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1. The treatment group received the pestle needle therapy, with manual stimulation at Yaoshu (DU2), Mingmen (DU4), Changqiang (DU1), Chengshan (BL57), Erbai (EX-UE2) and the perianal points (1, 3, 5, 7, 9, and 11o'clock around the lesion); while the control group received a sham treatment with very light pressure. Three sessions of treatment were performed at 30 min, 4 h and 12 h after the surgery, and each lasted for 15 min. MAIN OUTCOME MEASURES: The primary outcome was post-operative pain measured with the visual analogue scale (VAS) at 12 h after surgery. The secondary outcomes included the VAS scores measured at 0.5, 2, 4, 6, 8, 24 and 48 h after surgery, the analgesic dose, the time and the VAS score of the patients' first defecation after surgery, as well as the Hamilton Rating Scale for Anxiety (HAMA) evaluated before discharge. RESULTS: The mean pain score of the treatment group was significantly lower than that of the control group (3.10 ± 1.27 vs 4.82 ± 1.29; P < 0.001) at 12 h after surgery. Compared with the control group, patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery (P = 0.002); and their HAMA scores before discharge were lower (4.07 ± 2.40 vs 5.10 ± 2.45, P = 0.009). Compared to the treatment group, patients in the control group had a greater time to the first defecation after surgery ([52.34 ± 15.72] h vs [27.08 ± 13.68] h; P < 0.001), but there was no difference in their VAS scores at the first defecation (P = 0.092). CONCLUSION: The pestle needle therapy was effective for relieving pain, reducing anxiety and improving bowel function after hemorrhoidectomy, and it is worthy of clinical application.

[Effects of mild moxibustion on angiogenesis and microcirculation in wound repair after operation of anal fistula in rats].

OBJECTIVE: To observe the effects of mild moxibustion on angiogenesis and microcirculation in wound repair after operation of anal fistula, and to explore the mechanism of action. METHODS: Seventy-two SD male rats were made to bear an "acute, open, bleeding, infected" wound surface and were divided randomly into mild moxibustion group, microwave group and control group (24 rats per group). The wound surfaces of the treatment groups were treated for 15 min with mild moxibustion or microwave medical instrument from the first day after operation, and the control group was not given any treatment. At the first, third, seventh and fourteenth days after operation (1, 3, 7 and 14 days of treatment), six rats in each group were sacrificed after examining the blood flow of the wound surface, and the samples of granulation tissues were collected. The numbers of CD34 and positive expression of vascular endothelial growth factor (VEGF) in granulation tissues were detected. RESULTS: In the early and middle stages of wound healing, mild moxibustion could obviously increase the expression of VEGF, the number of CD34, and the blood flow of the wound surface. And the expression of VEGF, the number of CD34, and the blood flow of the wound surface began to increase at the third day, and reached the peak level at the seventh day, and then began to decrease. In the late stage of wound healing (day 14), mild moxibustion could decrease the expression of VEGF, the number of CD34, and decrease the blood flow of the wound surface. There were significant differences between the mild moxibustion group and the control group in the blood flow of the wound surface, the expression of VEGF and the numbers of CD34 in granulation tissues (P<0.05) after treatment, and except the number of CD34 at 14-day treatment, there were also differences between the mild moxibustion group and the microwave group. CONCLUSION: Mild moxibustion has better regulative actions on blood flow of the wound surface and the number of CD34 and positive expression of VEGF in granulation tissues, and can regulate microcirculation in wound surface and promote the wound healing.

[Reflection on development of integrated traditional Chinese and Western medicine].

After half a century of self-innovation, the integrated traditional Chinese and Western medicine has witnessed the great progress in both clinical and basic research. However, the theoretical system of the integrative medicine does not break through the limitations of traditional Chinese medicine and Western medicine, which hinders its implication in experimental study and clinical work. In view of the current situation, to develop the integration of traditional Chinese and Western medicine further, efforts should be made in such aspects as educational system construction, talent personnel training, improving the level of clinical practice and corresponding basic research as well as the establishing the basic theoretical system.

A review: therapeutic potential of adipose-derived stem cells in cutaneous wound healing and regeneration.

As the most important barrier for the human body, the skin often suffers from acute and chronic injuries, especially refractory wounds, which seriously affect the quality of life of patients. For these refractory wounds that cannot be cured by various surgical methods, stem cell transplantation becomes an effective research direction. As one of the adult stem cells, adipose-derived stem cells play an indispensable role in the repair of skin wounds more than other stem cells because of their advantages such as immune compatibility and freedom from ethical constraints. Here, we actively explore the role of adipose-derived stem cells in the repair of cutaneous wound and conclude that it can significantly promote cutaneous wound healing and regeneration. Based on a large number of animal and clinical trials, we believe that adipose-derived stem cells will have a greater breakthrough in the field of skin wound repair in the future, especially in chronic refractory wounds.

Effects of electroacupuncture combined with stem cell transplantation on anal sphincter injury-induced faecal incontinence in a rat model.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) and acupuncture are known to mitigate tissue damage. This study aimed to investigate the therapeutic effects of combined electroacupuncture (EA) stimulation and BMSC injection in a rat model of anal sphincter injury-induced faecal incontinence (FI). METHODS: 60 Sprague-Dawley rats were randomly divided into five groups: sham-operated control, FI, FI+EA, FI+BMSC, and FI+BMSC+EA. The anorectal tissues were collected on days 1, 3, 7 and 14. Repair of the injured anal sphincter was compared using haematoxylin and eosin (HE) and immunocytochemiscal analyses with sarcomeric α actinin. The expression of stromal cell derived factor-1 (SDF-1) and monocyte chemoattractant protein-3 (MCP-3) was detected by quantitative reverse transcription PCR to evaluate the effects of EA on the homing of BMSCs. RESULTS: The therapeutic effect of combined EA+BMSCs on damaged tissue was the strongest among all the groups as indicated by HE and immunohistochemical staining. The expression of SDF-1 and MCP-3 was significantly increased by combined EA and BMSC treatment when compared with the other groups (P=0.01 to P<0.05), suggesting promotive effects of EA on the homing of BMSCs. CONCLUSION: The combination of EA and BMSC transplantation effectively repaired the impaired anal sphincters. The underlying mechanism might be associated with apparent promotive effects of EA on the homing of BMSCs. Our study provides a theoretical basis for the development of a non-surgical treatment method for FI secondary to muscle impairment.

MicroRNA-145 regulates the proliferation, migration and invasion of human primary colon adenocarcinoma cells by targeting MAPK1.

Primary colon adenocarcinoma is responsible for high rates of mortality worldwide. The late diagnosis and lack of reliable biomarkers and therapeutic targets forms a bottleneck in the treatment of colon cancer. In the present study, the therapeutic potential of an important microRNA (miR), namely miR­145, was investigated in primary colon adenocarcinoma cells. The results revealed that the expression of miR­145 was significantly (P<0.05) downregulated in colon adenocarcinoma cells and the ectopic expression of miR­145 in colon cancer inhibited proliferation by promoting the apoptosis of SW480 primary colon adenocarcinoma cells. Furthermore, bioinformatics analysis revealed that miR­145 exerts its effected by targeting mitogen­activated protein kinase (MAPK) in SW480 cells. This was confirmed by expression analysis wherein the expression of MAPK1 was significantly (P<0.05) upregulated in the primary colon adenocarcinoma cells and the ectopic expression of miR­145 inhibited the expression of MAPK1. By contrast, the silencing of MAPK1 had similar effects on the proliferation, migration and invasion of SW480 cells as that of the overexpression of miR­145. Furthermore, it was observed that the inhibition of miR­145 did not reverse the effects of MAPK1 silencing on SW480 cells. However, the overexpression of MAPK1 led to considerable reversal of the effects of the overexpression of miR­145 on the proliferation, migration and invasion of SW480 cells. The effects of the overexpression of miR­145 were also evaluated in vivo in xenografted mice and it was observed that the overexpression of miR­145 also inhibited tumor growth and volume in vivo. Taken together, it was concluded that miR­145 may prove to be an important therapeutic target for colon cancer.

[Clinical research of thread-dragging through fistula method in treating patients with simple anorectal fistula].

OBJECTIVE: To evaluate the efficacy and safety of thread-dragging through fistula method in treating patients with simple anorectal fistula. METHODS: In this multi-centered, prospective, and randomized controlled clinical trial, 244 patients with simple low or high anorectal fistula were randomly divided into study group (with the method of thread-dragging through fistula) and control group (with the method of incision or thread-drawing). The healing time and curative rate of anorectal fistula, and the integral calculus of clinical symptom and life quality evaluations before and after treatment were all examined. The maximal anal canal squeeze pressure was measured to compare the therapeutic safety between these two groups. The health economical benefits were also assessed to determine which therapeutic method was more economical. RESULTS: The curative rate of simple low and high anorectal fistula were of no significant differences between the study group and the control group. The healing time of simple low anorectal fistula in the study group and the control group were (22.26+/-8.67) d and (31.41+/-11.39) d respectively, while the healing time of simple high anorectal fistula in the study group and the control group were (24.73+/-8.15) d and (32.20+/-12.60) d respectively, and there revealed significant differences between these two groups. Each integral calculus of clinical symptom evaluation in the study group was not obviously different from those in the control group besides the integral calculus of anal sphincter function. The integral calculus of life quality between the study group and the control group of simple low anorectal fistula had no significant differences. The integral calculus of anal sphincter function and confidence in treatment in the study group of high anorectal fistula were better than those in the control group. The hospitalization expense of the study group was remarkably lower than that of the control group. The maximal anal canal squeeze pressure in the study group after treatment was not reduced obviously as compared with that in the same group before treatment, while it was decreased significantly in the control group after treatment as compared with those in the same group before treatment and in the study group after treatment. CONCLUSION: The method of thread-dragging through fistula in treating simple low and high anorectal fistula can shorten the course of the disease, save the hospitalization expenses, improve the life quality of the patients, and protect the anal sphincter function.

[Application and development of suture-dragging therapy for anal fistula].

Traditional Chinese surgical treatment "suture-dragging" therapy is based on medical thread therapy and tight seton drainage in combination of minimal invasive surgical principle. It can preserve the integrity of anal sphincter musculature involved in fistulous tract or abscess and maintain anal function. This article not only describes in detail about the operation points and mechanisms of "suture-dragging" therapy of anorectal fistula, but also reviews the application and modification of anorectal disease.