Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion.

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.

Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis.

BACKGROUND: Postoperative peritoneal adhesion (PPA), characterized by abdominal pain, female infertility, and even bowel obstruction after surgery, has always been a major concern. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms underlying the basis of microarray data profile, followed by peritoneal adhesion formation, are largely unknown. AIM: To reveal the underlying pathogenesis of PPA at the molecular level. METHODS: The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis. We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods. We performed quantitative PCR and western blotting in vivo to validate the results preliminarily. RESULTS: In total, 446 expressed genes were altered in peritoneal adhesion. We found that several hub genes (e.g., tumor necrosis factor, interleukin 1 beta, interleukin 6, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2) were marked as significant biomarkers. Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway. According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies, TLR4, myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa B (NF-κB) played essential roles in Toll-like signaling transduction. Here, we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion. The results of the microarray analysis were verified by the animal experiments. These findings may extend our understanding of the molecular mechanisms of PPA. CONCLUSION: The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA. Future studies are required to validate our findings.

HuoXueTongFu Formula Alleviates Intraperitoneal Adhesion by Regulating Macrophage Polarization and the SOCS/JAK2/STAT/PPAR-γ Signalling Pathway.

Intraperitoneal adhesion is a common complication after abdominal surgery, which seriously affects the quality of life of patients. HuoXueTongFu Formula (HXTF) plays an important role in the prevention and treatment of intraperitoneal adhesions. However, the molecular-related mechanisms are still not fully known. In this study, the model of Intrapetitoneal adhesion was established by cecum abrasion and treated with HXTF for one week. RAW264.7 cells were given LPS, IFN-γ, IL-4, HXTF-medicated serum, and PPAR-γ agonist/antagonist, respectively. Histopathology, flow cytometry, ELISA, real-time PCR, and Western blotting were used to further detect the related protein, M1/M2 polarization tendency, and PPAR-γ nuclear translocation. The deposition of collagen fibres reduced in the local area of rats after the operation with HXTF treatment. Similar to IL-4, HXTF induced a tendency for macrophages to polarize toward M2 and promoted peroxisome proliferator-activated receptor-gamma (PPAR-γ) nuclear translocation. Furthermore, the use of HXTF and PPAR-γ agonists downregulated macrophage M1 polarization-related factors IL-1, IL-6, and TNF-alpha and upregulated M2 polarization-related factors IL-4, IL-10, and TGF-beta 1. Meanwhile, the use of HXTF and PPAR-γ agonists downregulated the SOCS3/JAK2/STAT1 pathway and activated the SOCS1/STAT6/PPAR-γ pathway. These results show that HXTF may reduce intraperitoneal adhesion by inducing macrophage M2 polarization and regulating the SOCS/JAK2/STAT/PPAR-γ pathway.

Comparison of endoscopic submucosal dissection with surgical gastrectomy for early gastric cancer: An updated meta-analysis.

BACKGROUND: There are several surgical options for treating early gastric cancers (EGCs), such as endoscopic resection, laparoscopic or open gastrectomy with D1 or D2 lymphadenectomy. Endoscopic resection for EGC with low risk of lymph node metastasis has been widely accepted as a therapeutic alternative. The role of endoscopic submucosal dissection (ESD) in treating EGC is not well established, especially when compared with resection surgery cases in a long-term follow-up scope. AIM: To compare the safety and efficacy of the short- and long-term outcomes between ESD and resection surgery. METHODS: We searched the databases of PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1990 to June 2018, enrolling studies reporting short- or long-term outcomes of ESD in comparison with resection surgery for EGC. The quality of the studies was assessed by the Newcastle-Ottawa Quality Assessment Scale. Stata software (version 12.0) was used for the analysis. Pooling analysis was conducted using either fixed- or random-effects models depending on heterogeneity across studies. RESULTS: Fourteen studies comprising 5112 patients were eligible for analysis (2402 for EGC and 2710 for radical surgery). Our meta-analysis demonstrated that the ESD approach showed advantages through decreased operation time [weighted mean difference (WMD): -140.02 min, 95%CI: -254.23 to -34.82 min, P = 0.009], shorter hospital stay (WMD: -5.41 d, 95% CI: -5.93 to -4.89 d, P < 0.001), and lower postoperative complication rate [Odds ratio (OR) = 0.39, 95%CI: 0.28-0.55, P < 0.001). Meanwhile, EGC patients who underwent ESD had higher recurrence rate (OR = 9.24, 95%CI: 5.94-14.36, P < 0.001) than resection surgery patients. However, the long-term survival including overall survival [Hazard ratio (HR) = 0.51, 95%CI: 0.26-1.00, P = 0.05] and event-free survival (HR = 1.59, 95%CI: 0.66-9.81, P = 0.300) showed no significant differences between these two groups. CONCLUSION: In the treatment of EGC, ESD was safe and feasible in comparison with resection surgery, with advantages in several surgical and post-operative recovery parameters. Although the recurrence rate was higher in ESD group, the long-term survival was still comparable in these two groups, suggesting ESD could be recommended as standard treatment for EGC with indications.

Assessment of postoperative adhesion formation in a rat cecum model using different techniques.

Adhesion-related complications after abdominal surgery bring out momentous morbidity and costs. Outcomes from animal experiments investigating prevention of adhesions are limited due to lack of consistency in existing animal models. Different intraperitoneal adhesion models were compared the inter observer variability was evaluated to seek for best model. Forty male SD rats weighting 250-300g were included and assigned randomly to four groups with diverse techniques, (A) postoperative adhesion cecum rat model abraded with sterile rasp; (B) postoperative adhesion cecum rat model abraded with sterile dry gauze; (C) postoperative adhesion cecum rat model abraded with sterile blade; (D) postoperative adhesion cecum rat model abraded with vascular clamp. Macroscopic adhesion scores were evaluated by Bigatti scoring system, and the incidence of adhesion were surveyed on the 7th day after the surgery. The results showed that four techniques currently used Bigatti adhesion scoring system are subjective, the sterile rasp is the most consistent and reproducible tool to establish an intraperitoneal adhesion model which is helpful for related studies and the development of new substances for adhesion prevention in the future.

Daucosterol protects neurons against oxygen-glucose deprivation/reperfusion-mediated injury by activating IGF1 signaling pathway.

We previously reported that daucosterol (a sterolin) up-regulates the expression of insulin-like growth factor I (IGF1)(1) protein in neural stem cells. In this study, we investigated the effects of daucosterol on the survival of cultured cortical neurons after neurons were subjected to oxygen and glucose deprivation and simulated reperfusion (OGD/R)(2), and determined the corresponding molecular mechanism. The results showed that post-treatment of daucosterol significantly reduced neuronal loss, as well as apoptotic rate and caspase-3 activity, displaying the neuroprotective activity. We also found that daucosterol increased the expression level of IGF1 protein, diminished the down-regulation of p-AKT(3) and p-GSK-3ß(4), thus activating the AKT(5) signal pathway. Additionally, it diminished the down-regulation of the anti-apoptotic proteins Mcl-1(6) and Bcl-2(7), and decreased the expression level of the pro-apoptotic protein Bax(8), thus raising the ratio of Bcl-2/Bax. The neuroprotective effect of daucosterol was inhibited in the presence of picropodophyllin (PPP)(9), the inhibitor of insulin-like growth factor I receptors (IGF1R)(10). Our study provided information about daucosterol as an efficient and inexpensive neuroprotectants, to which the IGF1-like activity of daucosterol contributes. Daucosterol could be potentially developed as a medicine for ischemic stroke treatment.