The flavonoid glycoside vaccarin inhibits adipogenesis and stimulates lipolysis via Hedgehog signaling in 3T3-L1 adipocytes

Vaccarin,a flavonoid glycoside isolated from Vaccaria segetalis,is non-toxic to 3T3-L1 cells up to concentrations of 200μM.Accordingly,we investigated the effects of this natural product on adipogenesis and lipolysis in 3T3-L1 adipocytes.Our results revealed that vaccarin significantly inhibited lipid accumulation by suppressing the adipogenesis-related transcription factors peroxisome proliferator-activated receptorγ(PPARγ)and the CCAAT/enhancer-binding proteinα(C/EBPα).Specifically,lipid accumulation decreased by up to 27.7±2.7%when 3T3-L1 adipocytes were treated with a 10μM concentration of vaccarin.Mechanistic studies showed that the compound inhibited adipogenesis through activation of the Hedgehog(Hh)signaling pathway and so restoring Smo and Gli1 expression at an early stage of differentiation.In mature 3T3-L1 cells,vaccarin significantly increased the secretion of glycerol into the surrounding medium and thus indicating that it accelerated the degradation of triglycerides.In addition,vaccarin,was shown to enhance lipolysis through stimulation of the transcription levels of lipoprotein lipase,monoglycerides lipase,adipose triacylglyceride lipase,hormone-sensitive lipase and adipose differentiated-related protein.All told,vaccarin suppressed lipid accumulation and enhanced lipolysis during adipocyte differentiation by restoring Hh signaling.As such,it is a phytochemical capable of halting adipocyte hyperplasia and,thereby,ameliorating the effects of obesity.

Risk factors for sporadic colorectal cancer in southern Chinese

AIM:To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index(BMI) in sporadic colorectal cancer in southern Chinese.METHODS:A hospital-based case-control study was conducted from July 2002 to December 2008.There were 706 cases and 723 controls with their sex and age(within 5 years) matched.An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.RESULTS:No positive association was observed between smoking status and sporadic colorectal cancer risk.Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer(CRC)(adjusted OR = 8.61 and 95% CI = 6.15-12.05;adjusted OR = 2.30, 95% CI = 1.27-4.17).Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer(adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.39, 95% CI = 1.10-1.75).Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers(adjusted OR = 7.60 and 95% CI = 5.13-11.25;adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI ≥ 24.0 kg/m2(adjusted OR = 1.38 and 95% CI = 1.04-1.83;adjusted OR = 1.35 and 95% CI = 1.02-1.79).The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer(adjusted OR = 2.51 and 95% CI = 1.24-5.07;adjusted OR = 1.82 and 95% CI = 1.17-2.82).CONCLUSION:Alcohol drinking, high BMI(≥ 24.0 kg/m2) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

Increased risk of colorectal neoplasia in inflammatory bowel disease patients with post-inflammatory polyps:A systematic review and meta-analysis

BACKGROUND Inflammatory bowel disease(IBD)patients with post-inflammatory polyps(PIPs)may carry an increased risk of colorectal neoplasia(CRN)including dysplasia and cancer.Current guidelines recommend active colonoscopy follow-up for these patients.However,the evidence for guidelines is still poor.In addition,some recent high-quality reports present a different view,which challenges the current guidelines.We hypothesize that IBD patients with PIPs are at increased risk of CRN.AIM To evaluate the risk of CRN in IBD patients with and without PIPs.METHODS A systematic search of PubMed,Embase,Cochrane Library,and Web of Science was performed to identify studies that compared the risk of CRN in IBD patients with and without PIPs.In addition,we screened the reference lists and citation indices of the included studies.Quality assessment was performed using the Newcastle–Ottawa Scale.Pooled odds ratio(OR)was calculated using the random-effects model to explore the final pooled effect size of the included studies and determine whether PIPs increase the risk of CRN.Sensitivity analysis,subgroup analysis,and assessment of publication bias were performed to examine the sources of heterogeneity.RESULTS Twelve studies with 5819 IBD patients,including 1281(22.01%)with PIPs,were considered eligible for this meta-analysis.We found that IBD patients with PIPs were at an increased risk of CRN as compared to those without PIPs[OR 2.01;95%confidence interval(CI):1.43–2.83].The results were similar when colorectal cancer was used as the study endpoint(OR 2.57;95%CI:1.69–3.91).Furthermore,the risk of CRN was still increased(OR 1.80;95%CI:1.12–2.91)when restricted to ulcerative colitis patients.Heterogeneity was high among the included studies(I^(2)=75%).Subgroup analysis revealed that the high heterogeneity was due to the study design.Sensitivity analysis showed that the main statistical outcomes did not essentially change after excluding any one of the included studies.No significant publication bias was found in the funnel plots.CONCLUSION IBD patients with PIPs have an increased risk of CRN as compared with those without PIPs,which support the current guidelines.However,a high-quality randomized controlled trial is warranted.

Risk factors for recurrence after bowel resection for Crohn’s disease

BACKGROUND Complications of Crohn’s disease such as intestinal obstruction,fistula or perforation often need surgical treatment.Nearly 70%-80%patients with Crohn’s disease would receive surgical treatment during the lifetime.However,surgical treatment is incurable for Crohn’s disease.The challenge of recurrence postoperatively troubles both doctors and patients.Over 50%patients would suffer recurrence postoperatively.Some certain risk factors are associated with recurrence of Crohn’s disease.AIM To evaluate the risk factors for endoscopic recurrence and clinical recurrence after bowel resection in Crohn’s disease.METHODS Patients diagnosed Crohn’s disease and received intestinal resection between April 2007 and December 2013 were included in this study.Data on the general demographic information,preoperative clinical characteristics,surgical information,postoperative clinical characteristics were collected.Continuous data are expressed as median(inter quartile range),and categorical data as frequencies and percentages.Kaplan-Meier method was applied to estimate the impact of the clinical variables above on the cumulative rate of postoperative endoscopic recurrence and clinical recurrence,then log-rank test was applied to test the homogeneity of those clinical variables.Multivariate Cox proportional hazard regression analysis was performed to identify the risk factors of postoperative endoscopic recurrence and clinical recurrence.RESULTS A total of 64 patients were included in this study.The median follow-up time for the patients was 17(9.25-25.75)mo.In this period,41 patients(64.1%)had endoscopic recurrence or clinical recurrence.Endoscopic recurrence occurred in 34(59.6%)patients while clinical recurrence occurred in 28(43.8%)patients,with the interval between the operation and recurrence of 13.0(8.0-24.5)months and 17.0(8.0-27.8)mo,respectively.In univariate analysis,diagnosis at younger age(P<0.001),disease behavior of penetrating(P=0.044)and preoperative use of anti-tumor necrosis factor(TNF)(P=0.020)were significantly correlated with endoscopic recurrence,while complication with perianal lesions(P=0.032)and preoperative use of immunomodulatory(P=0.031)were significantly correlated with clinical recurrence.As to multivariate analysis,diagnostic age(P=0.004),disease behavior(P=0.041)and preoperative use of anti-TNF(P=0.010)were independent prognostic factors for endoscopic recurrence,while complication with perianal lesions(P=0.023)was an independent prognostic factor for clinical recurrence.CONCLUSION Diagnostic age,disease behavior,preoperative use of anti-TNF and complication with perianal lesions were independent risk factors for postoperative recurrence in Crohn’s disease.

Overexpression of G protein-coupled receptor 31 as a poor prognosticator in human colorectal cancer

AIM To investigate the expression of G protein-coupled receptor 31 (GPR31) and its clinical significance in human colorectal cancer (CRC).METHODS To determine the association between the GPR31 expression and the prognosis of patients, we obtained paraffin-embedded pathological specimens from 466 CRC patients who underwent initial resection. A total of 321 patients from the First Affiliated Hospital of Sun Yat-sen University from January 1996 to December 2008 were included as a training cohort, whereas 145 patients from the Sixth Affiliated Hospital of Sun Yat-sen University from January 2007 to November 2008 were included as a validation cohort. We examined GPR31 expression levels in CRC tissues from two independent cohorts via immunohistochemical staining. All patients were categorized into either a GPR31 low expression group or a GPR31 high expression group. The clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group were compared.RESULTS We compared the clinicopathological factors and the prognosis of patients in the GPR31 low expression group and GPR31 high expression group. Significant differences were observed in the number of patients in pM classification between patients in the GPR31 low expression group and GPR31 high expression group (P = 0.007). The five-year survival and tumor-free survival rates of patients were 84.3% and 82.2% in the GPR31 low expression group, respectively, and both rates were 59.7% in the GPR31 high expression group (P < 0.05). Results of the Cox proportional hazard regression model revealed that GPR31 upregulation was associated with shorter overall survival and tumor-free survival of patients with CRC (P < 0.05). Multivariate analysis identified GPR31 expression in colorectal cancer as an independent predictive factor of CRC patient survival (P < 0.05).CONCLUSION High GPR31 expression levels were found to be correlated with pM classification of CRC and to serve as an independent predictive factor of poor survival of CRC patients.

The microbiome in inflammatory bowel diseases:from pathogenesis to therapy

Inflammatory bowel disease(IBD)has become a global disease with accelerating incidence worldwide in the 21st century while its accurate etiology remains unclear.In the past decade,gut microbiota dysbiosis has consistently been associated with IBD.Although many IBDassociated dysbiosis have not been proven to be a cause or an effect of IBD,it is often hypothesized that at least some of alteration in microbiome is protective or causative.In this article,we selectively reviewed the hypothesis supported by both association studies in human and pathogenesis studies in biological models.Specifically,we reviewed the potential protective bacterial pathways and species against IBD,as well as the potential causative bacterial pathways and species of IBD.We also reviewed the potential roles of some members of mycobiome and virome in IBD.Lastly,we covered the current status of therapeutic approaches targeting microbiome,which is a promising strategy to alleviate and cure this inflammatory disease.

Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019(COVID-19)pandemic,the gut microbiome in COVID-19 has garnered substantial interest,given its significant roles in human health and pathophysiology.Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19,including the bacterial microbiome,mycobiome,and virome.Overall,the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19,together with a decrease in gut microbiome diversity.Beyond the existence of severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2),the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria,fungi,and eukaryotic viruses,which are also associated with disease severity and presentation.Meanwhile,a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19.Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution,coinciding with‘long COVID’(also known as postacute sequelae of COVID-19).The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu.The impaired host immunity and distorted gut microbial ecology,particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida,may hinder the reassembly of the gut microbiome post COVID-19.Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection,as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.

International consensus on natural orifice specimen extraction surgery(NOSES)for gastric cancer(2019)

At present,natural orifice specimen extraction surgery(NOSES)has attracted more and more attention worldwide,because of its great advantages including minimal cutaneous trauma and post-operative pain,fast post-operative recovery,short hospital stay,and positive psychological impact.However,NOSES for the treatment of gastric cancer(GC)is still in its infancy,and there is great potential to improve its theoretical system and clinical practice.Especially,several key points including oncological outcomes,bacteriological concerns,indication selection,and standardized surgical procedures are raised with this innovative technique.Therefore,it is necessary to achieve an international consensus to regulate the implementation of GC-NOSES,which is of great significance for healthy and orderly development of NOSES worldwide.

Bone marrow-derived CXCR4-overexpressing MSCs display increased homing to intestine and ameliorate colitis-associated tumorigenesis in mice

Background and Objective:Increasing interest has developed in the therapeutic potential of bone marrow-derived mesenchymal stem cells(MSCs)for the treatment of inflammatory bowel disease(IBD)and IBD-induced cancer.However,whether MSCs have the ability to suppress or promote tumor development remains controversial.The stromal cell-derived factor 1(SDF-1)/C-X-C chemokine receptor type 4(CXCR4)axis is well known to play a critical role in the homing of MSCs.In this study,we aimed to evaluate the role of CXCR4-overexpressing MSCs on the tumorigenesis of IBD.Methods:MSCs were transduced with lentiviral vector carrying either CXCR4 or green fluorescent protein(GFP).Chemotaxis and invasion assays were used to detect CXCR4 expression.A mouse model of colitis-associated tumorigenesis was established using azoxymethane and dextran sulfate sodium(DSS).The mice were divided into three groups and then injected with phosphate buffer saline(PBS),MSC-GFP or MSC-CXCR4.Results:Compared with the mice injected with MSC-GFP,the mice injected with MSC-CXCR4 showed relieved weight loss,longer colons,lower tumor numbers and decreased tumor load;expression of pro-inflammatory cytokines decreased,and signal transducer and activator of transcription 3(STAT3)phosphorylation level in colon tissue was down-regulated.Conclusion:CXCR4-overexpressing MSCs exhibited effective anti-tumor function,which may be associated with enhanced homing to inflamed intestinal tissues.

Male gender is associated with an increased risk of anastomotic leak in rectal cancer patients after total mesorectal excision

Background:The impact of a patient’s gender on the development of anastomotic leak(AL)in rectal cancer patients following total mesorectal excision(TME)remains controversial.The aim of this study was to evaluate the association between patients’gender and the risk of AL.Methods:All rectal cancer patients following TME with a primary anastomosis during the study period from 2010 to 2014 were examined.Comparisons of the post-operative AL incidence rate between male and female patients were performed.Results:Of all patients examined(n¼956),587(61.4%)were males and 369(38.6%)were females.Male patients were more likely to have a history of smoking and drinking alcohol,but less likely to have a history of abdominal surgery compared to female patients.A higher incidence rate of pre-operative bowel obstruction and larger tumor volume in male patients was observed in our study.Of all the patients,81(8.5%)developed post-operative AL.More male patients(n¼62,10.6%)suffered from AL than females(n¼19,5.1%)(P¼0.003).Multivariate logistic regression analyses confirmed the association between male gender and AL[odds ratio(OR):2.41,95%confidence interval(CI):1.37–4.23,P¼0.002].Similar results were also obtained in patients who underwent laparoscopic TME(OR:2.11,95%CI:1.15–3.89,P¼0.016).Conclusions:Male patents were found to have an increased risk for AL following TME with a primary anastomosis.A temporary protecting stoma may help to protect the anastomosis and lessen the risk for AL especially in male patients.

Nomogram for predicting pathological complete response and tumor downstaging in patients with locally advanced rectal cancer on the basis of a randomized clinical trial

Background:Preoperative fluoropyrimidine with radiotherapy was regarded as the standard of care for locally advanced rectal cancer(LARC).The model for predicting pCR in LARC patients was based on standard treatment only.This study aimed to establish a nomogramwith pretherapeutic parameters and different neoadjuvant regimens for predicting pathologic complete response(pCR)and tumor downstaging or good response(ypT0-2N0M0)after receiving neoadjuvant treatment in patients with LARC based on a randomized clinical trial.Methods:Between January 2011 and February 2015,309 patients with rectal cancer were enrolled from a prospective randomized study(NCT01211210).All pretreatment clinical parameters were collected to build a nomogram for predicting pCR and tumor downstaging.The model was subjected to bootstrap internal validation.The predictive performance of the model was assessed with concordance index(C-index)and calibration plots.Results:Of the 309 patients,53(17.2%)achieved pCR and 132(42.7%)patients were classified as tumor downstaging with ypT0-2N0M0.Based on the logistic-regression analysis and clinical consideration,tumor length(P=0.005),tumor circumferential extent(P=0.036),distance from the anal verge(P=0.019),and neoadjuvant treatment regimen(P<0.001)showed independent association with pCR following neoadjuvant treatment.The tumor length(P=0.015),tumor circumferential extent(P=0.001),distance from the anal verge(P=0.032),clinical T category(P=0.012),and neoadjuvant treatment regimen(P=0.001)were significantly associated with good tumor downstaging(ypT0-2N0M0).Nomograms were developed to predict the probability of pCR and tumor downstaging with a C-index of 0.802(95%confidential interval[CI],0.736-0.867)and 0.730(95%CI,0.672-0.784).Internal validation revealed good performance of the calibration plots.Conclusions:The nomogramprovided individual prediction responses to different preoperative treatment for patients with rectal cancer.This model might help physicians in selecting an optimized treatment,but warrants further external validation.

Massive Preparation of Coumarone-indene Resin-based Hyper-crosslinked Polymers for Gas Adsorption

Hyper-crosslinked polymers （HCPs） are promising materials for gas capture and storage because of their low cost and easy preparation. In this work, we report the massive preparation of coumarone-indene resin-based hyper-crosslinked polymers via one-step Friedel-Crafts alkylation. Low-cost coumarone-indene resin serves as the new building block and chloroform is employed as both solvent and external crosslinker. A maximum surface area of 966 m2·g-1 is achieved, which is comparable with that of previously-reported coal tar-based porous organic polymers. Most importantly, a large number of heteroatoms including inherent oxygen atoms and introduced chlorine atoms in obtianed HCPs further enhance the interaction between specific sorbate molecule and adsorbent. Therefore, optimal structural and chemical property endow the new coumarone-indene resin-based HCPs with decent gas storage capacity （14.60 wt% at 273 K and 0.1 MPa for CO2; 1.18 wt% at 77.3 K and 0.1 MPa for H2）. These results demonstrate that new HCPs are potential candidates for applications in CO2 and H2 capture.

Easily-injectable shear-thinning hydrogel provides long-lasting submucosal barrier for gastrointestinal endoscopic surgery

Submucosal injection material has shown protective effect against gastrointestinal injury during endoscopic surgery in clinic.However,the protective ability of existing submucosal injection material is strictly limited by their difficult injectability and short barrier time.Herein,we report a shear-thinning gellan gum hydrogel that simultaneously has easy injectability and long-lasting barrier function,together with good hemostatic property and biocompatibility.Shear-thinning property endows our gellan gum hydrogel with excellent endoscopic injection performance,and the injection pressure of our gellan gum hydrogel is much lower than that of the small molecule solution(50 wt%dextrose)when injected through the endoscopic needle.More importantly,our gellan gum hydrogel shows much stronger barrier retention ability than normal saline and sodium hyaluronate solution in the ex vivo and in vivo models.Furthermore,our epinephrine-containing gellan gum hydrogel has a satisfactory hemostatic effect in the mucosal lesion resection model of pig.These results indicate an appealing application prospect for gellan gum hydrogel utilizing as a submucosal injection material in endoscopic surgery.

First preclinical experience with the newly developed EDGE SP1000 single-port robotic surgical system-assisted transanal total mesorectal excision

Introduction With advances in technology,natural orifice transluminal endoscopic surgery(NOTES)has long been an ultimate clinical pursuit in minimally invasive surgery.The transanal total mesorectal excision(taTME)in rectal surgery has been considered a representative example of the adoption of the NOTES concept[1,2].The taTME procedures offer an optimized view,better exposure of the anatomical plane.

Elevated preoperative CA125 is associated with poor survival in patients with metastatic colorectal cancer undergoing primary tumor resection:a retrospective cohort study

Background The impact of the preoperative carbohydrate antigen 125(CA125)level on the survival of metastatic colorectal cancer(CRC)patients undergoing primary tumor resection(PTR)remains uncertain.The aim of this study was to assess the prognostic value in overall survival(OS)and cancer-specific survival(CSS)between patients with and without an elevated preoperative CA125 level.Methods All metastatic CRC patients receiving PTR between 2007 and 2017 at the Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)were retrospectively included.OS and CSS rates were compared between patients with and without elevated preoperative CA125 levels.Results Among 326 patients examined,46(14.1%)exhibited elevated preoperative CA125 levels and the remaining 280(85.9%)had normal preoperative CA125 levels.Patients with elevated preoperative CA125 levels had lower body mass index,lower preoperative albumin level,lower proportion of preoperative chemotherapy,higher carcinoembryonic antigen and carbohydrate antigen 19–9(CA19–9)levels,poorer differentiation,and more malignant histopathological type than patients with normal preoperative CA125 levels.In addition,patients with elevated preoperative CA125 levels exhibited more advanced pathological T and N stages,more peritoneal metastasis,and more vessel invasion than patients with normal preoperative CA125 levels.Moreover,the primary tumor was more likely to be located at the colon rather than at the rectum in patients with elevated CA125 levels.Both OS and CSS rates in patients with elevated preoperative CA125 levels were significantly lower than those in patients with normal preoperative CA125 levels.Multivariate Cox regression analysis revealed that an elevated preoperative CA125 level was significantly associated with poor prognosis in metastatic CRC patients undergoing PTR.The hazard ratio(HR)in OS was 2.36(95%confidence interval[CI],1.67–3.33,P<0.001)and the HR in CSS was 2.50(95%CI,1.77–3.55,P<0.001).The survival analysis stratified by peritoneal metastasis also demonstrated that patients with elevated preoperative CA125 levels had lower OS and CSS rates regardless of peritoneal metastasis.Conclusion Based on an analysis of metastatic CRC patients undergoing PTR,an elevated preoperative CA125 level was associated with poor prognosis,which should be taken into consideration in clinical practice.

ARTICLE OPEN Mutant KRAS triggers functional reprogramming of tumor-associated macrophages in colorectal cancer

Oncogenic KRAS has been previously identified to act in a cell-intrinsic manner to modulate multiple biological functions of colorectal cancer(CRC).Here,we demonstrate a cell-extrinsic role of KRAS,where KRAS engages with the tumor microenvironment by functional reprogramming of tumor-associated macrophages(TAMs).In human CRC specimens,mutant KRAS positively correlates with the presence of TAMs.Mutationally activated KRAS in tumor cells reprograms macrophages to a TAM-like phenotype via a combination effect of tumor-derived CSF2 and lactate.In turn,KRAS-reprogrammed macrophages were shown to not only promote tumor progression but also induce the resistance of tumor cells to cetuximab therapy.Mechanistically,KRAS drives the production of CSF2 and lactate in tumor cells by stabilizing hypoxia-inducible factor-la(HIF-1a),a transcription factor that controls the expression of CSF2 and glycolytic genes.Mutant KRAS increased the production of reactive oxygen species,an inhibitor of prolyl hydroxylase activity which decreases HIF-1a hydroxylation,leading to enhanced HIF-1a stabilization.This cell-extrinsic mechanism awards KRAS a critical role in engineering a permissive microenvironment to promote tumor malignancy,and may present new insights on potential therapeutic defense strategies against mutant KRAS tumors.

Association of tumor differentiation and prognosis in patients with rectal cancer undergoing neoadjuvant chemoradiation therapy

Background and objective:Neoadjuvant chemoradiation therapy(NCRT)followed by radical resection has been a common practice for patients with locally advanced rectal cancer.This study aimed to analyse the association of tumor differentiation and prognosis in rectal-cancer patients undergoing NCRT.Methods:Patients with locally advanced,non-mucinous rectal cancer who underwent NCRT followed by radical resection between 2007 and 2017 were identified from an electronic health record system at the Sixth Affiliated Hospital of Sun Yatsen University(Guangzhou,China).Multivariable logistic regression and multivariate Cox regression were performed to analyse the association of response to NCRT and survival with clinicopathological characteristics of all these patients.Results:We identified 325 patients(241 males and 84 females;mean age,54.4611.2 years)who underwent NCRT followed by radical resection,including 26(8.0%)with poorly-differentiated rectal cancer,182(56.0%)with moderately-differentiated cancer and 117(36.0%)with well differentiated cancer.Propensity score matching analysis and multivariable logistic regression analysis results showed that tumor differentiation was significantly associated with response to NCRT.In the poor differentiation and non-poor differentiation groups,the 3-year overall survival(OS)rates were 74.6 and 93.5%,respectively,whereas the 3-year local recurrence rates were 18.6 and 3.7%,respectively.Multivariable Cox regression analyses revealed that poor differentiation was an independent risk factor for local recurrence and OS.Conclusions:Among the patients with locally advanced,non-mucinous rectal cancer,the patients with poorlydifferentiated cancer who underwent NCRT had a worse response to NCRT and poorer prognosis than those with moderately-and well-differentiated diseases.

Risk factors for recurrence of colorectal conventional adenoma and serrated polyp

Background Removal of colorectal polyps during screening could reduce the incidence of colorectal cancer(CRC).However,there is a lack of data on risk factors associated with recurrence of polyps,including conventional adenomas and serrated polyps(SPs).This study aimed to determine risk factors for recurrence of colorectal polyps and their subtypes based on the characteristics of the patients and polyps.Methods A total of 1,165 patients diagnosed with conventional adenoma or SP in the Sixth Affiliated Hospital of Sun Yat-sen University between January 2013 and December 2019 were enrolled in this study,including 668 cases with conventional adenomas,385 with SPs,and 112 with coexistence of adenomas and SPs.Univariate analysis and multivariate logistic regression were used to identify potential risk factors for polyp recurrence.A nomogram was established according to risk factors and the performance was evaluated using calibration plots.Results During a median follow-up of 24 months,recurrent polyps were observed in 531(45.6%)cases.Male,age≥50 years,body mass index(BMI)≥24 kg/m^(2),at least three polyps,smoking,alcohol consumption,family history of polyps,and family history of CRC were independent risk factors for polyp recurrence.The Harrell’s C-index of the nomogram developed with these parameters was 0.69 and the calibration plots showed good agreement between actual polyp recurrence and nomogram-predicted recurrence probability.In the subtype analyses,conventional adenomas had the same risk factors for recurrence as all polyps,while smoking,alcohol consumption,family history of polyps,and family history of CRC were not risk factors for SP recurrence.Conclusions We identified several risk factors for recurrence of colorectal polyps and found that some of them could increase the risk of adenoma recurrence but not SP recurrence,including smoking,alcohol consumption,and family history of polyps/CRC,which might help us to understand different etiology and biology between conventional adenomas and SPs.

Association between the nasopharyngeal microbiome and metabolome in patients with COVID-19

SARS-CoV-2,the causative agent for COVID-19,infect human mainly via respiratory tract,which is heavily inhabited by local microbiota.However,the interaction between SARS-CoV-2 and nasopharyngeal microbiota,and the association with metabolome has not been well characterized.Here,metabolomic analysis of blood,urine,and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients,and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19.Results showed lactic acid,L-proline,and chlorogenic acid methyl ester(CME)were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones.Nasopharyngeal commensal bacteria including Gemella morbillorum,Gemella haemolysans and Leptotrichia hofstadii were notably depleted in the pharynges of COVID-19 patients,while Prevotella histicola,Streptococcus sanguinis,and Veillonella dispar were relatively increased.The abundance of G.haemolysans and L.hofstadii were significantly positively associated with serum CME,which might be an anti-SARS-CoV-2 bacterial metabolite.This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility.The findings were based on a very limited number of patients enrolled in this study;a larger size of cohort will be appreciated for further investigation.

Bone marrow metastasis from advanced gastric cancer complicated with disseminated intravascular coagulation:a highly aggressive but manageable disease subtype

Dear Editor,Gastric cancer(GC)is the fifth most commonly diagnosed cancer and the fourth cause of cancer-related death worldwide[1,2].It has a greater prevalence in Eastern Asia,compared to other parts of the world,whereby more than two-thirds of the cases are diagnosed as advanced gastric cancer(AGC)[3].Disseminated intravascular coagulation(DIC)is a clinicopathologic syndrome characterized by laboratory evidence of platelets and clotting factors consumption,and proteolytic degradation.