Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

Full robot-assisted gastrectomy with intracorporeal robot-sewn anastomosis produces satisfying outcomes

AIM:To evaluate the feasibility and safety of full robotassisted gastrectomy with intracorporeal robot handsewn anastomosis in the treatment of gastric cancer.METHODS:From September 2011 to March 2013,110consecutive patients with gastric cancer at the authors’institution were enrolled for robotic gastrectomies.According to tumor location,total gastrectomy,distal or proximal subtotal gastrectomy with D2 lymphadenectomy was fully performed by the da Vinci Robotic Surgical System.All construction,including Roux-en-Y jejunal limb,esophagojejunal,gastroduodenal and gastrojejunal anastomoses were fully carried out by the intracorporeal robot-sewn method.At the end of surgery,the specimen was removed through a 3-4 cm incision at the umbilicus trocar point.The details of the surgical technique are well illustrated.The benefits in terms of surgical and oncologic outcomes are well documented,as well as the failure rate and postoperative complications.RESULTS:From a total of 110 enrolled patients,radical gastrectomy could not be performed in 2 patients due to late stage disease;1 patient was converted to laparotomy because of uncontrollable hemorrhage,and1 obese patient was converted due to difficult exposure;2 patients underwent extra-corporeal anastomosis by minilaparotomy to ensure adequate tumor margin.Robot-sewn anastomoses were successfully performed for 12 proximal,38 distal and 54 total gastrectomies.The average surgical time was 272.52±53.91 min and the average amount of bleeding was 80.78±32.37 mL.The average number of harvested lymph nodes was 23.1±5.3.All specimens showed adequate surgical margin.With regard to tumor staging,26,32 and 46 patients were staged asⅠ,ⅡandⅢ,respectively.The average hospitalization time after surgery was 6.2 d.One patient experienced a duodenal stump anastomotic leak,which was mild and treated conservatively.One patient was readmitted for intra-abdominal infection and was treated conservatively.Jejunal afferent loop obstruction occurred in 1 patient,who underwent re-operation and recovered quickly.CONCLUSION:This technique is feasible and can produce satisfying postoperative outcomes.It is also convenience and reliable for anastomoses in gastrectomy.Full robotic hand-sewn anastomosis may be a minimally invasive technique for gastrectomy surgery.

Barrier-focused intervention to increase colonoscopy attendance among nonadherent high-risk populations

AIM： To increase attendance tor colonoscopy among nonadherent high-risk individuals for colorectal cancer （CRC） screening in China. METHODS： During the first 12 mo without intervention, only 428 of the 2398 high-risk subjects attended a scheduled colonoscopy examination. The 1970 subjects who did not attend for CRC screening were enrolled in the present study. Prior barrier investigation was performed to ascertain the reasons for nonadherence. A barrier-focused intervention program was then established and implemented among eligible nonadherent subjects by telephone interviews and on-site consultations. The completion rates of colonoscopy during the first 12 mo without intervention and the second 12 mo with intervention were compared. Variations in the effect of the intervention on some high-risk factors and barrier characteristics were analyzed using logistic regression. RESULTS： 540 subjects who were not eligible were excluded from the study. The colonoscopy attendance rate was 23.04% （428/1858） during the first 12 mo without intervention, and 37.69% （539/1430） during the second 12 mo with intervention （P 〈 0.001）. Logistic regression analysis showed that the intervention was more effective among subjects with only objective barriers （OR： 34.590, 95% CI： 23.204-51.563） or subjects with some specific highrisk characteristics： first-degree relatives diagnosed with CRC （OR： 1.778, 95% CI： 1.010-3.131）, personal history of intestinal polyps （OR： 3.815, 95% CI： 1.994-7.300） and positive result for immunochemical fecal occult blood testing （OR： 2.718, 95% CI： 1.479-4.996）. CONCLUSION： The barrier-focused telephone or on- site consultation intervention appears to be a feasible means to improve colonoscopy attendance among nonadherent high-risk subjects for CRC screening in China.

Helicobacter pylori plays a key role in gastric adenocarcinoma induced by spasmolytic polypeptide-expressing metaplasia

Heliobacter pylori(H. pylori), a group 1 human gastric carcinogen, is significantly associated with chronic gastritis, gastric mucosal atrophy, and gastric cancer.Approximately 20% of patients infected with H. pylori develop precancerous lesions, among which metaplasia is the most critical. Except for intestinal metaplasia(IM), which is characterized by goblet cells appearing in the stomach glands, one type of mucous cell metaplasia, spasmolytic polypeptide-expressing metaplasia(SPEM), has attracted much attention. Epidemiological and clinicopathological studies suggest that SPEM may be more strongly linked to gastric adenocarcinoma than IM. SPEM, characterized by abnormal expression of trefoil factor 2, mucin 6, and Griffonia simplicifolia lectin II in the deep glands of the stomach, is caused by acute injury or inflammation. Although it is generally believed that the loss of parietal cells alone is a sufficient and direct cause of SPEM, further in-depth studies have revealed the critical role of immunosignals.There is controversy regarding whether SPEM cells originate from the transdifferentiation of mature chief cells or professional progenitors. SPEM plays a functional role in the repair of gastric epithelial injury. However, chronic inflammation and immune responses caused by H. pylori infection can induce further progression of SPEM to IM, dysplasia, and adenocarcinoma. SPEM cells upregulate the expression of whey acidic protein 4-disulfide core domain protein 2 and CD44 variant 9, which recruit M2 macrophages to the wound. Studies have revealed that interleukin-33, the most significantly upregulated cytokine in macrophages, promotes SPEM toward more advanced metaplasia. Overall, more effort is needed to reveal the specific mechanism of SPEM malignant progression driven by H.pylori infection.

＂Fast-track＂ and ＂Minimally Invasive＂ Surgery for Gastric Cancer

Background：Enhanced recovery after surgery （ERAS） protocols or fast-track （FT） programs enable a shorter hospital stay and lower complication rate.Minimally invasive surgery （MIS） is associated with a lesser trauma and a quicker recovery in many elective abdominal surgeries.However,little is known of the safety and effectiveness made by ERAS protocols combined with MIS for gastric cancer.The purpose of this study was to evaluate the safety and effectiveness made by FT programs and MIS in combination or alone.Methods：We summarized an 11-year experience on gastric cancer patients undergoing elective laparotomy or minimally invasive gastric resection in standard cares （SC） or FT programs during January 2004 to December 2014.A total of 984 patients were enrolled and assigned into four groups：open gastrectomies （OG） with SC （OG ＋ SC group,n =167）;OG with FT programs （OG ＋ FT group,n =277）;laparoscopic gastrectomies （LG） with FT programs （LG ＋ FT group,n =248）;and robot-assisted gastrectomies （RG） with FT programs （RG ＋ FT group,n =292）.Patients＆#39; data were collected to evaluate the clinical outcome.The primary end point was the length of postoperative hospital stay.Results：The OG ＋ SC group showed the longest postoperative hospital stay （mean：12.3 days,median：11 days,interquartile range [IQR]：6-16 days）,while OG ＋ FT,LG ＋ FT,and RG ＋ FT groups recovered faster （mean：7.4,6.4,and 6.6 days,median：6,6,and 6 days,IQR：3-9,4-8,and 3-9 days,respectively,all P 〈 0.001）.The postoperative rehabilitation parameters such as flatus time after surgery （4.7 ± 0.9,3.1 ± 0.8,3.0± 0.9,and 3.1 ± 0.9 days） followed the same manner.After 30 postoperative days＆#39; follow-up,the total incidence of complications was 9.6% in OG ＋ SC group,10.1% in OG ＋ FT group,8.1% in LG ＋ FT group,and 10.3% in RG ＋ FT group.The complications showed no significant differences between the four groups （all P 〉 0.05）.Conclusions：ERAS protocols alone could significantly bring fast recovery after surgery regardless of the surgical technique.MIS further reduces postoperative hospital stay.It is safe and effective to apply ERAS protocols combined with MIS for gastric cancer.

Avoidance of urinary drainage during perioperative period of open elective colonic resection within enhanced recovery after surgery programme

Background:Urinary catheterization(UC)is a conventional perioperative measure for major abdominal operation.Optimization of perioperative catheter management is an essential component of the enhanced recovery after surgery(ERAS)programme.We aimed to investigate the risk factors of urinary retention(UR)after open colonic resection within the ERAS protocol and to assess the feasibility of avoiding urinary drainage during the perioperative period.Methods:A total of 110 colonic-cancer patients undergoing open elective colonic resection between July 2014 and May 2018 were enrolled in this study.All patients were treated within our ERAS protocol during the perioperative period.Data on patients’demographics,clinicopathologic characteristics,and perioperative outcomes were collected and analysed retrospectively.Results:Sixty-eight patients(61.8%)underwent surgery without any perioperative UC.Thirty patients(27.3%)received indwelling UC during the surgical procedure.Twelve(10.9%)cases developed UR after surgery necessitating UC.Although patients with intraoperative UC had a lower incidence of post-operative UR[0%(0/30)vs 15%(12/80),P=0.034],intraoperative UC was not testified as an independent protective factor inmultivariate logistic analysis.The history of prostatic diseases and the body mass index were strongly associated with post-operative UR.Six patients were diagnosed with post-operative urinary-tract infection,among whom two had intraoperative UC and four were complicated with post-operative UR requiring UC.Conclusion:Avoidance of urinary drainage for open elective colonic resection is feasible with the implementation of the ERAS programme as the required precondition.Obesity and a history of prostatic diseases are significant predictors of postoperative UR.