PTPRD/PTPRT mutation correlates to treatment outcomes of immunotherapy and immune landscape in pan-cancers

Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) cohort.Results: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from immunotherapy.Conclusions: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.

Impact of duration of adjuvant chemotherapy in radically resected patients with T4bN1-3M0/TxN3bM0 gastric cancer

AIM To provide evidence regarding the postoperative treatment of patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer, for which guidelines have not been established. METHODS Patients who had undergone curative resection between 1996 and 2014 with a pathological stage of T4 b N1-3 M0/Tx N3 b M0 for gastric cancer were retrospectively analyzed; staging was based on the 7 th edition of the American Joint Committee on Cancer staging system. The clinicopathological characteristics, administration of adjuvant chemotherapy, and patterns of recurrence were studied. Univariate and multivariate analyses of prognostic factors were conducted. The chemotherapeutic agents mainly included fluorouropyrimidine, platinum and taxanes, used as monotherapy, doublet, or triplet regimens. Patterns of first recurrence were categorized as locoregional recurrence, peritoneal dissemination, or distant metastasis.RESULTS The 5-year overall survival(OS) of the whole group(n = 176) was 16.8%, and the median OS was 25.7 mo(95%CI: 20.9-30.5). Lymphovascular invasion and a node positive rate(NPR) ≥ 0.8 were associated with a poor prognosis(P = 0.01 and P = 0.048, respectively). One hundred forty-seven(83.5%) of the 176 patients eventually experienced recurrence; the most common pattern of the first recurrence was distant metastasis. The prognosis was best for patients with locoregional recurrence and worst for those with peritoneal dissemination. Twelve(6.8%) of the 176 patients did not receive adjuvant chemotherapy, while 164(93.2%) patients received adjuvant chemotherapy. Combined chemotherapy, including doublet and triplet regimens, was associated with a better prognosis than monotherapy, with no significant difference in 5-year OS(17.5% vs 0%, P = 0.613). The triplet regimen showed no significant survival benefit compared with the doublet regimen for 5-year OS(18.5% vs 17.4%, P = 0.661). Thirty-nine(22.1%) patients received adjuvant chemotherapy for longer than six months; the median OS in patients who received adjuvant chemotherapy for longer than six months was 40.2 mo(95%CI: 30.6-48.2), significantly longer than the 21.6 mo(95%CI: 19.1-24.0) in patients who received adjuvant chemotherapy for less than six months(P = 0.001).CONCLUSION Patients with T4 b N1-3 M0/Tx N3 b M0 gastric cancer showed a poor prognosis and a high risk of distant metastasis. Adjuvant chemotherapy for longer than six months improved outcomes for them.

Interpretation of breast cancer screening guideline for Chinese women

Breast cancer is the most common malignant tumor in Chinese women.Early screening is the best way to improve the rates of early diagnosis and survival of breast cancer patients.The peak onset age for breast cancer in Chinese women is considerably younger than those in European and American women.It is imperative to develop breast cancer screening guideline that is suitable for Chinese women.By summarizing the current evidence on breast cancer screening in Chinese women,and referring to the latest guidelines and consensus on breast cancer screening in Europe,the United States,and East Asia,the China Anti-Cancer Association and National Clinical Research Center for Cancer(Tianjin Medical University Cancer Institute and Hospital)have formulated population-based guideline for breast cancer screening in Chinese women.The guideline provides recommendations on breast cancer screening for Chinese women at average or high risk of breast cancer according to the following three aspects:age of screening,screening methods,and screening interval.This article provides more detailed information to support the recommendations in this guideline and to provide more direction for current breast cancer screening practices in China.

Development and validation of a three-long noncoding RNA signature for predicting prognosis of patients with gastric cancer

BACKGROUND Gastric cancer(GC)is one of the most frequently diagnosed gastrointestinal cancers throughout the world.Novel prognostic biomarkers are required to predict the prognosis of GC.AIM To identify a multi-long noncoding RNA(lncRNA)prognostic model for GC.METHODS Transcriptome data and clinical data were downloaded from The Cancer Genome Atlas.COX and least absolute shrinkage and selection operator regression analyses were performed to screen for prognosis associated lncRNAs.Receiver operating characteristic curve and Kaplan-Meier survival analyses were applied to evaluate the effectiveness of the model.RESULTS The prediction model was established based on the expression of AC007991.4,AC079385.3,and AL109615.2 Based on the model,GC patients were divided into“high risk”and“low risk”groups to compare the differences in survival.The model was re-evaluated with the clinical data of our center.CONCLUSION The 3-lncRNA combination model is an independent prognostic factor for GC.

A Comparative Study of the Short-Term Efficacy of Laparoscopic Radical Resection of Right-Sided Colon Cancer with Two Different Surgeon Positions and Trocar Placements

Objective: To investigate the short-term efficacy of laparoscopic radical resection of right-sided colon cancer with two different surgeon positions and trocar placements. Methods: The data of 78 patients who underwent laparoscopic radical resection of right-sided colon cancer between January 2018 and August 2019 were retrospectively analysed. The surgical method was selected by the patients. The patients were divided into two groups according to the surgeons’ positioning habits and trocar placements. The group with the lead surgeon standing between the patient’s legs had 35 patients, and the group with the lead surgeon standing at the left side of the patient had 43 patients. The operation time, intraoperative blood loss, postoperative anal gas evacuation time, postoperative urinary catheter indwelling time, postoperative hospital stay, C-reactive protein (CRP) level on the first day after surgery, and postoperative pathological data and complications were compared between the two groups. Results: All patients underwent the laparoscopic radical resection of right-sided colon cancer, none converting to laparotomy. No significant difference (P > 0.05) in intraoperative blood loss (57.6 ± 21.3 ml vs 60.2 ± 35.3 ml), postoperative anal gas evacuation time (3.5 ± 1.1 d vs 3.8 ± 1.3 d), postoperative urinary catheter indwelling time (2.6 ± 1.3 d vs 2.4 ± 1.2 d), postoperative hospital stay (7.1 ± 1.8 d vs 7.5 ± 2.1 d), or CRP level on the first day after surgery (54.7 ± 9.6 mg/L vs 53.9 ± 8.2 mg/L) was detected between the two groups. The operation time was shorter in the group with the lead surgeon standing between the patient’s legs (185.2 ± 25.6 min vs 196.2 ±19.7 min) (P < 0.05). The two groups did not differ significantly in the tumour length (4.2 ± 1.3 cm vs 3.9 ± 1.5 cm), number of dissected lymph nodes (27.5 ± 11.6 vs 25.1 ± 15.4), pathological type, or postoperative pathological tumour-node-metastasis stage (P > 0.05). No patients died or had anastomotic fistula during their postoperative hospital stay, and the incidence of postoperative complications did not differ between the two groups (22.9% (8/35) vs 23.3% (10/42);P > 0.05). Conclusion: Under the principle of radical resection, the surgeon should adopt the most suitable standing position and trocar placement according to the specific situation. If the surgeon stands between the patient’s legs, this might shorten the operation time and promote a smoother surgery.

Long noncoding RNA NALT1-induced gastric cancer invasion and metastasis via NOTCH signaling pathway

BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant phenotypes of GC mayhelp to elucidate the mechanism of tumor development and predict the prognosisof GC.AIMTo investigate the prognostic value of NOTCH1 associated with lncRNA in T cellacute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of itsinvolvement in GC invasion and metastasis.METHODSRNA sequencing and corresponding clinical data were downloaded from TheCancer Genome Atlas database. The significance module was studied byweighted gene coexpression network analysis. A total of 336 clinical sampleswere included in the study. Gene silencing, reverse transcription polymerasechain reaction, western blotting, scrape motility assay, and Transwell migrationassay were used to assess the function of hub-lncRNAs.RESULTSAt the transcriptome level, 3339 differentially expressed lncRNAs were obtained.weighted gene coexpression network analysis was used to obtain 15 lncRNAclusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hublncRNAof blue module and was an independent risk factor for GC prognosis.NALT1 was overexpressed in GC and its expression was closely related toinvasion and metastasis. The mechanism may involve NALT1 regulation ofNOTCH1, which is associated with lncRNA in T cell acute lymphoblasticleukemia, through cis regulation, thereby affecting the expression of the NOTCHsignaling pathway.CONCLUSIONNALT1 is overexpressed and promotes invasion and metastasis of GC. Themechanism may be related to regulation of NOTCH1 by NALT1 and its effect onNOTCH signaling pathway expression.

Prognostic impact of D2-plus lymphadenectomy and optimal extent of lymphadenectomy in advanced gastric antral carcinoma: Propensity score matching analysis

Objective: To investigate the prognostic impact of D2-plus lymphadenectomy including the posterior(No. 8 p,No. 12 b/p, No. 13, and No. 14 v), and para-aortic(No. 16 a2, and No. 16 b1) lymph nodes(LNs) in subtotal gastrectomy for advanced gastric antral carcinoma.Methods: A total of 203 patients with advanced gastric cancer(GC) located in the antrum, who underwent R0 gastrectomy with D2 or D2-plus lymphadenectomy between January 2003 and December 2011 were enrolled.Propensity score matching was used to reduce the strength of the confounding factors to accurately evaluate prognoses. The therapeutic value index(TVI) was calculate to evaluate the survival benefit of dissecting each LN station.Results: Of 102 patients with D2-plus lymphadenectomy, 21(20.59%) were pathologically identified as having LN metastases beyond the extent of D2 lymphadenectomy. After matching, the overall survival(OS) was significantly better in the D2-plus than the D2 group(P=0.030). In the multivariate survival analysis, D2-plus lymphadenectomy(hazard ratio, 0.516;P=0.006) was confirmed to significantly improve the survival rate. In the logistic regression analysis, p N stage [odds ratio(OR), 2.533;95% confidence interval(95% CI), 1.368-4.691;P=0.003] and extent of LNs metastasis(OR, 5.965;95% CI, 1.335-26.650;P=0.019) were identified as independent risk factors for LN metastases beyond the extent of D2 lymphadenectomy. The TVI of patient with metastasis to LNs station was 7.1(No. 8p), 5.7(No. 12p), 5.1(No. 13), and 7.1(both No. 16a2 and No. 16b1), respectively.Conclusions: D2-plus lymphadenectomy may improve the prognoses of some patients with advanced GC located in the antrum, especially for No. 8p, No. 12b, No. 13, and No. 16.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis:A multicenter propensity scorematched cohort study

Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.

CUL4 E3 ligase regulates the proliferation and apoptosis of lung squamous cell carcinoma and small cell lung carcinoma

Objective:The E3 ligase,CRL4,plays diverse roles in different cellular processes,such as DNA damage,transcriptional regulation,cell cycle progression,and cell apoptosis.Our previous study showed that CUL4A and CUL4B had a strong association with tobacco smoking risk in lung squamous cell carcinoma(SCC)and small cell lung carcinoma(SCLC).This study aimed to define the potential mechanism underlying the roles of CUL4A and CUL4B in the development of SCC and SCLC.Methods:We determined the role of CUL4A and CUL4B in the cell cycle and apoptosis of SCC and SCLC,and identified the key apoptosis-related gene involved in the oncogenic activity of CUL4B by Western blot,immunohistochemical staining,flow cytometry,and enzyme inhibition experiments.Results:We found that depletion of CUL4A and CUL4B reduced the proliferation of SCC and SCLC cells.cUL4Aknockdown but not CUL4Bknockdown arrested cells in Gl phase while upregulating P21 and cU L4Bknockdown promoted cell apoptosis through upregulation o f FOXO3A.Accordingly,CUL4B decreased FO X03A expression by activating the ERK signaling pathway and mediating FOXO3A degradation via the ubiquitin-proteasome pathway.Conclusions:These results identified the function of E3 ligase CRL4 in regulating SCC and SCLC cell proliferation,which provides a potential strategy for cancer therapy by targeting FOXO3A and the E3 ligase,CRL4.

Surgical intervention for malignant bowel obstruction caused by gastrointestinal malignancies

BACKGROUND Malignant bowel obstruction(MBO)is a common event for end-stage gastrointestinal cancer patients.Previous studies had demonstrated manifestations and clinical management of MBO with mixed malignancies.There still lack reports of the surgical treatment of MBO.AIM To analyze the short-term outcomes and prognosis of palliative surgery for MBO caused by gastrointestinal cancer.METHODS A retrospective chart review of 61 patients received palliative surgery between January 2016 to October 2018 was performed,of which 31 patients underwent massive debulking surgery(MDS)and 30 underwent ostomy/by-pass surgery(OBS).The 60-d symptom palliation rate,30-d morbidity and mortality,and overall survival rates were compared between the two groups.RESULTS The overall symptom palliation rate was 75.4%(46/61);patients in the MDS group had significantly higher symptom palliation rate than OBS group(90%vs 61.2%,P=0.016).Patients with colorectal cancer who were in the MDS group showed significantly higher symptom improvement rates compared to the OBS group(overall,76.4%;MDS,61.5%;OBS,92%;P=0.019).However,patients with gastric cancer did not show a significant difference in symptom palliation rate between the MDS and OBS groups(OBS,60%;MDS,80%;P=1.0).The median survival time in the MDS group was significantly longer than in the OBS group(10.9 mo vs 5.3 mo,P=0.05).CONCLUSION For patients with MBO caused by peritoneal metastatic colorectal cancer,MDS can improve symptom palliation rates and prolong survival,without increasing mortality and morbidity rates.

Elemene-containing hyperthermic intraperitoneal chemotherapy combined with chemotherapy for elderly patients with peritoneal metastatic advanced gastric cancer

BACKGROUND Almost all elderly patients with peritoneal metastatic gastric cancer(PGC)are unlikely to tolerate cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy(HIPEC)and adjuvant chemotherapy.However,determining how to optimize the treatment strategy for such patients has always been a clinical problem.Both HIPEC and palliative adjuvant chemotherapy can benefit patients with PGC.Therefore,optimizing HIPEC and chemotherapy regimens has potential clinical value in reducing side effects,and improving treatment tolerance and clinical effectiveness.AIM To explore the effect of HIPEC containing elemene,which is an anti-cancer component extracted in traditional Chinese herbal medicine,combined with reduced capecitabine and oxaliplatin(CapeOx)chemotherapy regimens,in elderly patients with PGC.METHODS In the present study,39 of 52 elderly PGC patients were included and assigned to different HIPEC treatment groups[lobaplatin group(group L)and mixed group(group M)]for analysis.Lobaplatin was used for all three HIPECs in group L.In group M,lobaplatin was used in the middle of the three HIPECs,and elemene was used for the first and third HIPEC.After HIPEC,patients received CapeOx chemotherapy.The incidence of complications(abdominal infection,lung infection,and urinary tract infection),myelosuppression,immune function(CD4/CD8 ratio),average length of hospital stay,and prognosis were compared between these two groups.RESULTS There was no significant difference in the incidence of complications between the two groups during hospitalization(P>0.05).Compared to patients in group M,patients in group L exhibited severe myelosuppression(P=0.027)and increased length of hospital stay(P=0.045).However,no overall survival benefit was observed in group M.Furthermore,the immune function of patients in group M was less affected(P<0.001),when compared to that of patients in group L.The multivariate analysis suggested that the cycles of chemotherapy after perfusion significantly affected the prognosis of patients in both groups.CONCLUSION Compared to the lobaplatin-based HIPEC regimen,the administration of elemene reduced the myelosuppression incidence in elderly PGC patients.The present study sheds light on the implementation of this therapeutic strategy for this set of patients.

Anatomical variation of infra-pyloric artery origination： A prospective multicenter observational study (IPA-Origin)

Objective： Infra-pyloric artery （IPA） is an important anatomical landmark in treatment of gastric cancer and is the key vessel for pylorus-preserving gastrectomy and subgroup of infra-pyloric lymph nodes. However, its anatomical variation is not thoroughly understood. Our study aimed to clarify the origination of the IPA. Methods： We did this prospective, multicenter, open-label, observational study at gastric surgery departments of 34 hospitals in China. Gastric cancer patients aged 18 years or older and scheduled to undergo elective total or distal gastrectomy were assigned. During the surgery, IPA dissecting and exposing the origination point with photographs or video clips were required. The primary outcome was the origination of the IPA. Analysis of variance, χ2 tests and Fisher＇s tests were used to analyze the differences between groups. The study is registered at Clinicaltrials.gov （No. NCT03071237）. Results： Between May 8 and July 31, 2017, 429 patients were assigned for the study, and 419 （97.7%） patients had the IPA dissected and recorded through photograph or video and were included in the primary outcome analysis. The median age was 62 years old, and 73.7% were male. Among the patients, 78.5% received laparoscopic surgery. Single IPA origination was identified in 398 （95.0%） patients, including gastroduodenal artery （GDA） in 154 （36.8%） patients, anterior superior pancreaticoduodenal artery （ASPDA） in 130 （31.0%） patients, and right gastroepiploic artery （RGEA） in 114 （27.2%） patients. Fifteen （3.6%） patients were identified with multiple IPA and 6 （1.4%） patients were identified as IPA absence. The differences in the distribution of surgical approach （P=0.003） and geographic area （P=0.030） were statistically significant. No difference was shown in sex, age, gastrectomy type, tumor location, and clinical T, N and M stage. Conclusions： Our study found that the IPA originates from GDA, ASPDA and RGEA in similar proportions. Laparoscopic surgery may be more helpful in dissection of the IPA than open surgery.

Highlighted multi-modifications of enzymes:a novel succinylation mediated by histone acetyltransferase 1 in tumors

Histone acetyltransferase 1 serves as a succinyl transferase in tumors Protein post-translational modification(PTM)as an important research field has attracted increasing attention.Recently,our group has reported that histone acetyltransferase 1(HAT1)succinylated histones and non-histones and promoted tumorigenesis1.HAT1 plays a role in different biological processes,including cell cycle progression,glucose metabolism,histone production,and DNA damage repair2.We found that HAT1 succinylated histone H3 on K122.For a non-histone,HAT1 catalyzed the succinylation of phosphoglycerate mutase 1(PGAM1)on K99 to increase its enzyme activity,promoting glycolysis in cancer cells.Functionally,HAT1-mediated succinylation contributed to tumorigenesis.Our finding provided new insight into the mechanism of how a histone acetyltransferase HAT1 modulated succinylation during cancer development.

Efficacy of the Intraoperative Use of Indocyanine-Green Fluorescence Angiography in Laparoscopic Rectal Resections

Background: In traditional laparoscopic colorectal cancer surgery, the surgeon’s method assess intestinal stumps blood supply is subject to certain subjectivity and blindness. Indocyanine green (ICG) real-time blood perfusion fluorescence angiography in laparoscopic radical resection of rectal cancer has great potential clinical value and can visually judge intestinal tract blood supply to improve the surgery safety, reduce postoperative complications, and ensure the recovery of patients after surgery. Objective: To explore the efficacy of the intraoperative use of indocyanine-green fluorescence angiography in laparoscopic rectal resections in patients with rectal cancer. Methods: In the present study, 109 rectal cancer patients were included and assigned to different surgical groups [ICG and control groups] for analysis. Statistical analysis was carried out for various common postoperative complications in the two groups. Finally, the patients in the ICG fluorescence imaging group had a timely adjustment of the proximal resection of the intestinal tube before the proximal bowel of the lesion was cut off when the intestinal blood supply was insufficiently assessed by fluorescence imaging. Two subgroups, the adjustment and the non-adjustment groups, were analyzed. Results: Compared with the control group, the postoperative anal ventilation time in the ICG group was shorter than that in the control group (P 0.05). In addition, the postoperative complications were lower than those in the control group, and the differences were statistically significant (P 0.05). However, the distance between the tumor from the anal verge in the adjustment group was smaller than that in the non-adjustment group, and the difference was statistically significant (P 0.01). Conclusion: Compared with conventional laparoscopic radical resection of rectal cancer, ICG real-time indocyanine green fluore- scence angiography was safe and feasible. This technique is a promising intraoperative tool for the assessment of bowel perfusion especially suitable for patients with lower rectal cancer.

TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance

Immune checkpoint blockade(ICB)offers a new opportunity for treatment for gastric cancer(G.C.).Understanding the upstream regulation of immune checkpoints is crucial to further improve the efficacy of ICB therapy.Herein,using the CRISPR-Cas9-based genome-wide screening,we identified TRIM28 as one of the most significant regulators of PD-L1,a checkpoint protein,in G.C.cells.

H pylori status and angiogenesis factors in human gastric carcinoma

AIM: To investigate H pylori expression in gastric cancer patients in relation to primary tumor angiogenic markers, such as microvessel density (MVD), thymidine phospho- rylase (TP), vascular endothelial growth factor receptor-1 (VEGF-R1), p53 and circulating VEGF levels. METHODS: Angiogenic markers were analyzed immu- nohistochemically in 56 primary gastric cancers. H pylori cytotoxin (vacA) and the cytotoxin-associated gene (cagA) amplification were evaluated using PCR assay. Serum H pylori IgG antibodies and serum/plasma circulating VEGF levels were detected in 39 and 38 patients by ELI- SA, respectively. RESULTS: A total of 69% of patients were positive for circulating IgG antibodies against H pylori. cagA-positive H pylori strains were found in 41% of gastric patients. vacA was found in 50% of patients; s1 strains were more highly expressed among vacA-positive patients. The presence of the s1 strain was signifi cantly associ- ated with cagA (P = 0.0001). MVD was signifi cantly cor- related with both tumor VEGF expression (r = 0.361, P = 0.009) and serum VEGF levels (r = -0.347, P = 0.041).Conversely, neither VEGF-R1 expression nor MVD was related to p53 expression. However, H pylori was not related to any angiogenic markers except for the plasma VEGF level (P = 0.026). CONCLUSION: H pylori antigen is related to higher plasma VEGF levels, but not to angiogenic character- istics. It can be hypothesized that the toxic effects of H pylori on angiogenesis occurs in early preclinical dis- ease phase or in long-lasting aggressive infections, but only when high H pylori IgG levels are persistent.

Research progress in hepatitis B virus covalently closed circular DNA

Hepatitis B virus(HBV)infections are a global public health issue.HBV covalently closed circular DNA(cccDNA),the template for the transcription of viral RNAs,is a key factor in the HBV replication cycle.Notably,many host factors involved in HBV cccDNA epigenetic modulation promote the development of hepatocellular carcinoma(HCC).The HBV cccDNA minichromosome is a clinical obstacle that cannot be efficiently eliminated.In this review,we provide an update on the advances in research on HBV cccDNA and further discuss factors affecting the modulation of HBV cccDNA.Hepatitis B virus X protein(HBx)contributes to HBV cccDNA transcription and the development of hepatocarcinogenesis through modulating host epigenetic regulatory factors,thus linking the cccDNA to hepatocarcinogenesis.The measurable serological biomarkers of continued transcription of cccDNA,the effects of anti-HBV drugs on cccDNA,and potential therapeutic strategies targeting cccDNA are discussed in detail.Thus,this review describes new insights into HBV cccDNA mechanisms and therapeutic strategies for cleaning cccDNA,which will benefit patients with liver diseases.

iTRAQ-based quantitative analysis of cancer-derived secretory proteome reveals TPM2 as a potential diagnostic biomarker of colorectal cancer

Colorectal cancer （CRC） is a leading cause of cancer-related deaths worldwide. We aimed to find novel molecules as potential biomarkers for the early diagnosis of CRC. A serum-free conditioned medium was successfully collected from three pairs of CRC tissue and adjacent normal tissue, iTRAQ-based quantitative proteomic analysis was applied to compare the differences in secretome between primary CRC mucosa and adjacent normal mucosa. A total of 145 kinds of proteins were identified. Of these proteins, 29 were significantly different between CRC and normal tissue. Tropomyosin 2 p （TPM2） exhibited the most significant differences; as such, this protein was selected for further validation. Quantitative real-time PCR indicated that the mRNA expression of TPM2 significantly decreased in the CRC tissue compared with the paired adjacent normal tissue. Immunohistochemical analysis also confirmed that TPM2 was barely detected at protein levels in the CRC tissue. In summary, this study revealed potential molecules for future biomarker applications and provided an efficient approach for the differential analysis of cancer-associated secretome. TPM2 may be valuable for the early diagnosis of CRC.

Laparoscopic radical resection for situs inversus totalis with colonic splenic flexure carcinoma:A case report

BACKGROUND Situs inversus totalis(SIT)is a rare group of congenital developmental malformations in the clinical setting,with all organs in the chest and abdomen existing in a mirror image reversal of their normal positions.Few reports have described laparoscopic surgery for colorectal cancer in patients with SIT,and it is considered difficult even for an experienced surgeon because of the mirror positioning.We present a case report of laparoscopic radical resection of a colonic splenic flexure carcinoma in a patient with SIT.CASE SUMMARY A 72-year-old male was referred to our hospital with colonic splenic flexure carcinoma,and computed tomography showed that all the organs in the chest and abdomen were inverted.Laparoscopic hemicolectomy with complete mesocolic excision was safely performed.The operating surgeon stood on the patient’s left side,which is opposite of the normal location.CONCLUSION Abdominal computed tomography is an effective method for diagnosing SIT preoperatively in patients with colonic splenic flexure carcinomas.Laparoscopic radical resection is difficult,but it is well established and safe.The surgeon should stand in the opposite position and perform backhand operations.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer:a single-center,single-arm,prospective Phase II trial(PKUCH-R02)

Background:Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk,locally advanced rectal cancer.However,the benefit of more intensive total neoadjuvant treatment(TNT)is unknown.This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer.Methods:This was a single-center,single-arm,prospective Phase II trial in Peking University Cancer Hospital(Beijing,China).Patients received three cycles of induction oxaliplatin and capecitabine(CapeOX)followed by chemoradiotherapy and two cycles of consolidation CapeOX.The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate,completion of TNT,and pathological downstaging rate.Results:Between August 2017 and August 2018,68 rectal cancer patients with at least one high risk factor(cT3c/3d/T4a/T4b,cN2,mesorectal fascia involvement,or extramural venous invasion involvement)were enrolled.The overall compliance of receiving the entire treatment was 88.2%(60/68).All 68 patients received induction chemotherapy,65 received chemoradiotherapy,and 61 received consolidation chemotherapy.The Grade 3–4 adverse event rate was 30.8%(21/68).Nine patients achieved clinical complete response and then watch and wait.Five patients(7.4%)developed distant metastasis during TNT and received palliative chemotherapy.Fifty patients underwent surgical resection.The complete response rate was 27.9%.After a median follow-up of 49.2 months,the overall 3-year disease-free survival rate was 69.7%.Conclusions:For patients with high-risk rectal cancer,this TNT regimen can achieve favorable survival and complete response rates but with high toxicity.However,it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.