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Abstract Background Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators. Methods Patients’ baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients. Results A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets – “high-risk” and “low-risk” based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis. Conclusion The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.

Abstract Objective The current study used a composite outcome to investigate whether applying the ERAS protocol would enhance the recovery of patients undergoing laparoscopic total gastrectomy (LTG). Exposures Laparoscopic total gastrectomy and perioperative interventions were the exposure. An ERAS clinical pathway consisting of 14 items was implemented and assessed. Patients were divided into either ERAS-compliant or non-ERAS-compliant group according the adherence above 9/14 or not. Main outcomes and measures The primary study outcome was a composite outcome called ‘optimal postoperative recovery’ with the definition as below: discharge within 6 days with no sever complications and no unplanned re-operation or readmission within 30 days postoperatively. Univariate logistic regression analysis and multivariate logistic regression analysis were used to model optimal postoperative recovery and compliance, adjusting for patient-related and disease-related characteristics. Results A total of 252 patients were included in this retrospective study, 129 in the ERAS compliant group and 123 in the non-ERAS-compliant group. Of these, 79.07% of the patients in ERAS compliant group achieved optimal postoperative recovery, whereas 61.79% of patients in non-ERAS-compliant group did (P = 0.0026). The incidence of sever complications was lower in the ERAS-compliant group (1.55% vs. 6.5%, P = 0.0441). No patients in ERAS compliant group had unplanned re-operation, whereas 5.69% (7/123) of patients in non-ERAS-compliant group had (p = 0.006). The median length of the postoperative hospital stay was shorter in the in the ERAS compliant group (5.51 vs. 5.68 days, P = 0.01). Both logistic (OR 2.01, 95% CI 1.21–3.34) and stepwise regression (OR 2.07, 95% CI 1.25–3.41) analysis showed that high overall compliance with the ERAS protocol facilitated optimal recovery in such patients. In bivariate analysis of compliance for patients who had an optimal postoperative recovery, carbohydrate drinks (p = 0.0196), early oral feeding (P = 0.0043), early mobilization (P = 0.0340), and restrictive intravenous fluid administration (P

Abstract Background The symptoms of functional constipation (FC) were obviously affected by mental symptoms, which was consistent with somatic symptoms. However, the characteristics of FC patients with somatic symptom remains unexplored. Methods Clinical characteristics including somatic symptom (SOM, PHQ-15), depression (PHQ-9), anxiety (GAD-7), quality of life (PAC-QOL), constipation (KESS), demographic variables, anatomical abnormalities and symptoms were investigated. Subsequent analyses encompassed the comparison of clinical parameters between patients with SOM + group (PHQ-15 ≥ 10) and SOM- group (PHQ-15

Summary: Background: Recurrence following radical resection in patients with stage IB gastric cancer (GC) is not uncommon. However, whether postoperative adjuvant chemotherapy could reduce the risk of recurrence in stage IB GC remains contentious. Methods: We collected data on 2110 consecutive patients with pathologic stage IB (T1N1M0 or T2N0M0) GC who were admitted to 8 hospitals in China from 2009 to 2018. The survival of patients who received adjuvant chemotherapy was compared with that of postoperative observation patients using propensity score matching (PSM). Two survival prediction models were constructed to estimate the predicted net survival gain attributable to adjuvant chemotherapy. Findings: Of the 2110 patients, 1344 received adjuvant chemotherapy and 766 received postoperative observation. Following the 1-to-1 matching, PSM yielded 637 matched pairs. Among matched pairs, adjuvant chemotherapy was not associated with improved survival compared with postoperative observation (OS: hazard ratio [HR], 0.72; 95% CI, 0.52–1.00; DFS: HR, 0.91; 95% CI, 0.64–1.29). Interestingly, in the subgroup analysis, reduced mortality after adjuvant chemotherapy was observed in the subgroups with elevated serum CA19-9 (HR, 0.22; 95% CI, 0.08–0.57; P = 0.001 for multiplicative interaction), positive lymphovascular invasion (HR, 0.32; 95% CI, 0.17–0.62; P

Abstract Background Better predictors of patients with stage II/III gastric cancer (GC) most likely to benefit from adjuvant chemotherapy are urgently needed. This study aimed to assess the ability of CDX2 and mucin markers to predict prognosis and fluorouracil‐based adjuvant chemotherapy benefits. Methods CDX2 and mucin protein expressions were examined by immunohistochemistry and compared with survival and adjuvant chemotherapy benefits in a prospective evaluation cohort of 782 stage II/III GC patients. Then, the main findings were validated in an independent validation cohort (n = 386) and an external mRNA sequencing dataset (ACRG cohort, n = 193). Results In the evaluation cohort, CDX2, CD10, MUC2, MUC5AC, and MUC6 expressions were observed in 59.7%, 26.7%, 27.6%, 55.1%, and 57.7% of patients, respectively. However, only the expression of CDX2 was found to be associated with adjuvant chemotherapy benefits. Most importantly, CDX2‐negative patients had a poorer prognosis when treated with surgery only, while the prognosis of CDX2‐negative and CDX2‐positive patients was similar when receiving postoperative adjuvant chemotherapy. Further analysis revealed that patients with CDX2 negative tumors benefited from chemotherapy (5‐year overall survival rates: 60.0% with chemotherapy vs. 23.2% with surgery‐only, p

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

Abstract Background Flurbiprofen has been one of the most commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in China and other Asian countries for perioperative multimodal analgesia in recent years, yet its association with anastomotic leakage in gastrointestinal anastomoses is unknown. The current study was designed to investigate whether short-term administration of flurbiprofen would increase the risk of anastomotic leakage in patients undergoing gastrointestinal surgery for cancer resection. Methods A total of 3653 patients (2487 (66.1%) men) undergoing elective operation for gastrointestinal cancer between 18 July 2017 and 30 Oct 2020 were included. The median age was 61 years (interquartile range 53–67 years). The exposure was the short-term postoperative use of flurbiprofen (defined as flurbiprofen treatment within the first week after surgery). The primary outcome was the frequency of clinical anastomotic leakage. Results Of 3653 patients with available data who were included in the final analysis, 2282 received flurbiprofen administration, and 1371 did not. Anastomotic leakage was not significantly increased among the patients receiving flurbiprofen compared with those who did not (1.62% v 1.46%; P=0.70). In-hospital mortality was comparable between the two groups (0.04% v 0.07%; P=0.72). After adjusted analysis, male sex (OR 3.51, 95% CI 1.80–6.85), ASA score of 3–4 (OR 2.69, 95% CI 1.62–4.48), and intraoperative infusion (OR 2.24, 95% CI 1.19–4.21) were identified as risk factors for anastomotic leakage. Conclusions Postoperative short-term use of flurbiprofen did not increase the risk of anastomotic leakage in gastrointestinal anastomoses.

Abstract Background Pseudouridine synthase (PUS) 7 is a member of the PUS family that catalyses pseudouridine formation. It has been shown to be involved in intellectual development and haematological malignancies. Nevertheless, the role and the underlying molecular mechanisms of PUS7 in solid tumours, such as colorectal cancer (CRC), remain unexplored. This study elucidated, for the first time, the role of PUS7 in CRC cell metastasis and the underlying mechanisms. Methods We conducted immunohistochemistry, qPCR, and western blotting to quantify the expression of PUS7 in CRC tissues as well as cell lines. Besides, diverse in vivo and in vitro functional tests were employed to establish the function of PUS7 in CRC. RNA-seq and proteome profiling analysis were also applied to identify the targets of PUS7. PUS7-interacting proteins were further uncovered using immunoprecipitation and mass spectrometry. Results Overexpression of PUS7 was observed in CRC tissues and was linked to advanced clinical stages and shorter overall survival. PUS7 silencing effectively repressed CRC cell metastasis, while its upregulation promoted metastasis, independently of the PUS7 catalytic activity. LASP1 was identified as a downstream effector of PUS7. Forced LASP1 expression abolished the metastasis suppression triggered by PUS7 silencing. Furthermore, HSP90 was identified as a client protein of PUS7, associated with the increased PUS7 abundance in CRC. NMS-E973, a specific HSP90 inhibitor, also showed higher anti-metastatic activity when combined with PUS7 repression. Importantly, in line with these results, in human CRC tissues, the expression of PUS7 was positively linked to the expression of HSP90 and LASP1, and patients co-expressing HSP90/PUS7/LASP1 showed a worse prognosis. Conclusions The HSP90-dependent PUS7 upregulation promotes CRC cell metastasis via the regulation of LASP1. Thus, targeting the HSP90/PUS7/LASP1 axis may be a novel approach for the treatment of CRC.

ObjectiveWe aimed to investigate the association between fat mass to lean body mass ratio (RFL), percentage of body fat (PBF), and fat mass (FM) with mortality among middle-aged and elderly cancer patients without obesity.MethodsThis prospective hospital-based cohort study comprised 3,201 patients with stage I to IV cancer aged 40 years or above (mean age: 58 years for female patients and 61 years for male patients; mean length of follow-up was 1.67 years; the maximal follow-up length was 6.42 years). FM and PBF were measured by bioelectrical impedance analysis (BIA). Cox proportional hazard models were used, and adjusted hazard ratios (HRs) were estimated.ResultsWe revealed a significant association between RFL and all-cause mortality among men aged ≥60 years after adjusting for confounders. Compared with those in the lowest tertile of RFL, elderly men in the medium and highest tertile had a 35 and 34% lower hazard of death from any cause, respectively. After additionally adjusted for C-reaction protein (CRP), HRs of medium and high tertile of RFL became short of statistical significance [medium tertile: adjusted HRs (95% CI) = 0.74 (0.46, 1.20); highest tertile: adjusted HRs (95% CI) = 0.84 (0.53, 1.33)]. Among elderly women, RFL was significantly related to all-cause mortality only when the additional adjustment for CRP [medium tertile: adjusted HRs (95% CI) = 2.08 (1.08, 4.01); highest tertile: adjusted HRs (95% CI) = 0.90 (0.45, 1.81)]. No significant association between RFL and all-cause mortality was observed among female participants or male participants aged less than 60 years.ConclusionOur findings showed a significant non-linear association between RFL and all-cause mortality, which was observed only in elderly men, and might be attenuated by their inflammation state.

Tumor microenvironment (TME) is a key factor involved in cancer development and metastasis. In the TME of colorectal cancer (CRC), the gene expression status of stromal tissues could influence the CRC process from normal to adenoma then carcinoma; however, the expression status at the protein level has not yet been well evaluated. A total of 22 CRC patients were recruited for this study, and the tissue regions corresponding with adjacent, adenoma, and carcinoma were carefully excised by laser capture microdissection (LCM), including a patient with adenoma and carcinoma. The individual proteomes of this cohort were implemented by high-resolution mass spectrometer under data-independent acquisition (DIA) mode. A series of informatic analysis was employed to statistically seek the proteomic characteristics related with the stroma at different stages of CRC. The identified proteins in the colorectal stromal tissues were much less than and almost overlapped with that in the corresponding epithelial tissues; however, the patterns of protein abundance in the stroma were very distinct from those in the epithelium. Although qualitative and quantitative analysis delineated the epithelial proteins specifically typified in the adjacent, adenoma, and carcinoma, the informatics in the stroma led to another deduction that such proteomes were only divided into two patterns, adjacent- and adenoma/carcinoma-dependent. The comparable proteomes of colorectal adenoma and carcinoma were further confirmed by the bulk preparation- or individual LCM-proteomics. The biochemical features of the tumor stromal proteomes were characterized as enrichment of CD4+ and CD8+ T cells, upregulated pathways of antigen presentation, and enhancement of immune signal interactions. Finally, the features of lymphoid lineages in tumor stroma were verified by tissue microarray (TMA). Based on the proteomic evidence, a hypothesis was raised that in the colorectal tissue, the TME of adenoma and carcinoma were comparable, whereas the key elements driving an epithelium from benign to malignant were likely decided by the changes of genomic mutations or/and expression within it.

Colorectal cancer (CRC), ranking as the third commonest cancer, leads to extremely high rates of mortality. Metastasis is the major cause of poor outcome in CRC. When metastasis occurs, 5-year survival rates of patients decrease sharply, and strategies to enhance a patient’s lifetime seem limited. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that are significantly involved in manipulation of CRC malignant phenotypes, including proliferation, invasion, and metastasis. To date, accumulating studies have revealed the mechanisms and functions of certain miRNAs in CRC metastasis. However, there is no systematic discussion about the biological implications and clinical potential (diagnostic role, prognostic role, and targeted therapy potential) of metastasis-related miRNAs in CRC. This review mainly summarizes the recent advances of miRNA-mediated metastasis in CRC. We also discuss the clinical values of metastasis-related miRNAs as potential biomarkers or therapeutic targets in CRC. Moreover, we envisage the future orientation and challenges in translating these findings into clinical applications.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069–1.430; and HR: 1.600, 95% CI: 1.350–1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054–1.434; and HR: 1.658, 95% CI: 1.389–1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853–3.225) and RFS (HR: 2.405, 95% CI: 1.802–3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Abstract Background The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes. Methods A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer‐specific survival (CSS) and overall survival (OS). Results The incidence of diabetes was 7.6% in the whole population. In comparison with the non‐DM group, the DM group had greater body weight, but a similar fat‐free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG‐SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4‐year CSS, 62% vs 73%) and OS (4‐year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer‐specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070‐1.536) and overall (HR = 1.206, 95% CI 1.040‐1.399) mortality. Conclusions Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.

Abstract Background Endogenous retroelements (EREs) constitute about 42% of the human genome and have been implicated in common human diseases such as autoimmunity and cancer. The dominant paradigm holds that EREs are expressed in embryonic stem cells (ESCs) and germline cells but are repressed in differentiated somatic cells. Despite evidence that some EREs can be expressed at the RNA and protein levels in specific contexts, a system-level evaluation of their expression in human tissues is lacking. Methods Using RNA sequencing data, we analyzed ERE expression in 32 human tissues and cell types, including medullary thymic epithelial cells (mTECs). A tissue specificity index was computed to identify tissue-restricted ERE families. We also analyzed the transcriptome of mTECs in wild-type and autoimmune regulator (AIRE)-deficient mice. Finally, we developed a proteogenomic workflow combining RNA sequencing and mass spectrometry (MS) in order to evaluate whether EREs might be translated and generate MHC I-associated peptides (MAP) in B-lymphoblastoid cell lines (B-LCL) from 16 individuals. Results We report that all human tissues express EREs, but the breadth and magnitude of ERE expression are very heterogeneous from one tissue to another. ERE expression was particularly high in two MHC I-deficient tissues (ESCs and testis) and one MHC I-expressing tissue, mTECs. In mutant mice, we report that the exceptional expression of EREs in mTECs was AIRE-independent. MS analyses identified 103 non-redundant ERE-derived MAPs (ereMAPs) in B-LCLs. These ereMAPs preferentially derived from sense translation of intronic EREs. Notably, detailed analyses of their amino acid composition revealed that ERE-derived MAPs presented homology to viral MAPs. Conclusions This study shows that ERE expression in somatic tissues is more pervasive and heterogeneous than anticipated. The high and diversified expression of EREs in mTECs and their ability to generate MAPs suggest that EREs may play an important role in the establishment of self-tolerance. The viral-like properties of ERE-derived MAPs suggest that those not expressed in mTECs can be highly immunogenic.

Abstract Background Colorectal cancer (CRC) is the third most prevalent cancer in China but few large-scale studies were conducted to understand CRC patients. The current study is aimed to gain a real-world perspectives of CRC patients in China. Methods Using electronic medical records of sampled patients between 2011 and 2016 from 12 hospitals in China, a retrospective cohort study was conducted to describe demographics and disease prognosis of CRC patients, and examine treatment sequences among metastatic CRC (mCRC) patients. Descriptive, comparative and survival analyses were conducted. Results Among mCRC patients (3878/8136, 48%), the fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and other oxaliplatin-based regimens were the most widely-used first-line treatment (42%). Fluorouracil, leucovorin, irinotecan (FOLFIRI) and other irinotecan-based regimens dominated the second-line (40%). There was no a dominated regimen for the third-line. The proportion of patients receiving chemotherapy with targeted biologics increased from less than 20% for the first- and second- lines to 34% for the third-line (p

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide. Until now, the involved mechanisms during the development of ESCC are largely unknown. This study aims to explore the driven-genes and biological pathways in ESCC. Methods mRNA expression datasets of GSE29001, GSE20347, GSE100942, and GSE38129, containing 63 pairs of ESCC and non-tumor tissues data, were integrated and deeply analyzed. The bioinformatics approaches include identification of differentially expressed genes (DEGs) and hub genes, gene ontology (GO) terms analysis and biological pathway enrichment analysis, construction and analysis of protein–protein interaction (PPI) network, and miRNA–gene network construction. Subsequently, GEPIA2 database and qPCR assay were utilized to validate the expression of hub genes. DGIdb database was performed to search the candidate drugs for ESCC. Results Finally, 120 upregulated and 26 downregulated DEGs were identified. The functional enrichment of DEGs in ESCC were mainly correlated with cell cycle, DNA replication, deleted in colorectal cancer (DCC) mediated attractive signaling pathway, and Netrin-1 signaling pathway. The PPI network was constructed using STRING software with 146 nodes and 2392 edges. The most significant three modules in PPI were filtered and analyzed. Totally ten genes were selected and considered as the hub genes and nuclear division cycle 80 (NDC80) was closely related to the survival of ESCC patients. DGIdb database predicted 33 small molecules as the possible drugs for treating ESCC. Conclusions In summary, the data may provide new insights into ESCC pathogenesis and treatments. The candidate drugs may improve the efficiency of personalized therapy in future.

The high mobility group box (HMGB) protein family consists of four members: HMGB1, 2, 3, and 4. They share similar amino acid sequences and identical functional regions, especially HMGB1, 2, and 3. The homology in structure may lead to similarity in function. In fact, though their targets may be different, they all possess the fundamental function of binding and distorting target DNAs. However, further research confirmed they are distributed differently in tissues and involved in various distinct physiological and pathological cellular processes, including cell proliferation, division, migration, and differentiation. Recently, the roles of HMGB family members in carcinogenesis has been widely investigated; however, systematic discussion on their functions and clinical values in malignant tumors is limited. In this review, we mainly review and summarize recent advances in knowledge of HMGB family members in terms of structure, distribution, biochemical cascades, and specific mechanisms regarding tumor progression. Importantly, the diagnostic, prognostic, and therapeutic value of these proteins in cancers is discussed. Finally, we envisage the orientation and challenges of this field in further studies.

Drug resistance, whether intrinsic or acquired, often leads to treatment failure in esophageal squamous cell carcinoma (ESCC). Clarifying the mechanism of drug resistance in ESCC has great significance for reversing drug resistance, as well as improving the prognosis of patients. Previously, we demonstrated that etoposide-induced 2.4-kb mRNA (EI24) is the target of miR-483-3p, which promoted the growth, migration, and drug resistance in ESCC, suggesting that EI24 participates in repressing the tumorigenesis and progression of ESCC. Here, we observed that EI24 was remarkably decreased in ESCC tissues. Moreover, its expression was directly linked to the prognosis of patients. We then confirmed that the forced overexpression of EI24 repressed cell growth and sensitized ESCC cells to chemotherapeutic agents, whereas EI24 silencing had the opposite effect. Furthermore, gene microarray and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms and indicated that EI24 exerts a tumor-suppressive role via suppressing the acute phase response signaling pathway or IL-1 signaling pathway in ESCC. Collectively, our data reveal that EI24 overexpression attenuates malignant phenotypes of ESCC and that it is a novel possible ESCC therapeutic target.

Systemic chemotherapy is identified as a curative approach to prolong the survival time of patients with colorectal cancer (CRC). Although great progress in therapeutic approaches has been achieved during the last decades, drug resistance still extensively persists and serves as a major hurdle to effective anticancer therapy for CRC. The mechanism of multidrug resistance remains unclear. Recently, mounting evidence suggests that a great number of microRNAs (miRNAs) may contribute to drug resistance in CRC. Certain of these miRNAs may thus be used as promising biomarkers for predicting drug response to chemotherapy or serve as potential targets to develop personalized therapy for patients with CRC. This review mainly summarizes recent advances in miRNAs and the molecular mechanisms underlying miRNA-mediated chemoresistance in CRC. We also discuss the potential role of drug resistance-related miRNAs as potential biomarkers (diagnostic and prognostic value) and envisage the future orientation and challenges in translating the findings on miRNA-mediated chemoresistance of CRC into clinical applications.

Abstract Background Patient-derived organoids and xenografts (PDXs) have emerged as powerful models in functional diagnostics with high predictive power for anticancer drug response. However, limitations such as engraftment failure and time-consuming for establishing and expanding PDX models followed by testing drug efficacy, and inability to subject to systemic drug administration for ex vivo organoid culture hinder realistic and fast decision-making in selecting the right therapeutics in the clinic. The present study aimed to develop an advanced PDX model, namely MiniPDX, for rapidly testing drug efficacy to strengthen its value in personalized cancer treatment. Methods We developed a rapid in vivo drug sensitivity assay, OncoVee® MiniPDX, for screening clinically relevant regimens for cancer. In this model, patient-derived tumor cells were arrayed within hollow fiber capsules, implanted subcutaneously into mice and cultured for 7 days. The cellular activity morphology and pharmacokinetics were systematically evaluated. MiniPDX performance (sensitivity, specificity, positive and negative predictive values) was examined using PDX as the reference. Drug responses were examined by tumor cell growth inhibition rate and tumor growth inhibition rate in PDX models and MiniPDX assays respectively. The results from MiniPDX were also used to evaluate its predictive power for clinical outcomes. Results Morphological and histopathological features of tumor cells within the MiniPDX capsules matched those both in PDX models and in original tumors. Drug responses in the PDX tumor graft assays correlated well with those in the corresponding MiniPDX assays using 26 PDX models generated from patients, including 14 gastric cancer, 10 lung cancer and 2 pancreatic cancer. The positive predictive value of MiniPDX was 92%, and the negative predictive value was 81% with a sensitivity of 80% and a specificity of 93%. Through expanding to clinical tumor samples, MiniPDX assay showed potential of wide clinical application. Conclusions Fast in vivo MiniPDX assay based on capsule implantation was developed-to assess drug responses of both PDX tumor grafts and clinical cancer specimens. The high correlation between drug responses of paired MiniPDX and PDX tumor graft assay, as well as translational data suggest that MiniPDX assay is an advanced tool for personalized cancer treatment.

Abstract Background This meta-analysis is aimed to evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) programs in gastric cancer patients undergoing laparoscopy-assisted gastrectomy (LAG). Methods We performed a meta-analysis of randomized control trials involving either enhanced recovery after surgery (ERAS)/fast track surgery (FTS) for patients underwent LAG. EMBASE, Pubmed, Web of science, and Cochrane Library were searched. Primary outcomes included the length of postoperative hospital stay, cost of hospitalization, postoperative complications, and readmission rate. Results Five randomized control trials were eligible for analysis. There were 159 cases in FTS group and 156 cases in conventional care group. Compared with conventional care group, FTS group relates to shorter postoperative hospital stay (WMD − 2.16; 95% CI − 3.05 to − 1.26, P

Abstract The feasible of minimally invasive pancreaticoduodenectomy (MIPD) remains controversial when compared with open pancreaticoduodenectomy (OPD). We conducted a systemic review and meta-analysis to summarise the available evidence to compare MIPD vs OPD. We systemically searched PubMed, EMBASE and Web of Science for studies published through February 2016. The primary endpoint was postoperative pancreatic fistula (POPF, grade B/C). A total of 27 studies involving 14,231 patients (2,377 MIPD and 11,854 OPD) were included. MIPD was associated with longer operative times (P

Abstract Fatty liver (FL) is one of the risk factors for acute pancreatitis and is also indicative of a worse prognosis as compared to acute pancreatitis without fatty liver (AP). The aim of the present study was to analyze, at the hepatic level, the differentially expressed genes (DEGs) between acute pancreatitis with fatty liver (APFL) rats and AP rats. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses of these DEGs indicated that PPARα signalling pathway and fatty acid degradation pathway may be involved in the pathological process of APFL, which indicated that fatty liver may aggravate pancreatitis through these pathways. Moreover, the excessive activation of JAK/STAT signaling pathway and toll-like receptor signaling pathway was also found in APFL group as shown in heat map. In conclusion, the inhibition of PPARα signaling pathway and the fatty acid degradation pathway may lead to the further disorder of lipid metabolism, which can aggravate pancreatitis.

Background. The availability of an identical twin donor that allows avoidance of complications related to graft rejection and immunosuppression represents an ideal treatment option for irreversible intestinal failure. Methods and Results. We described a 45-year-old woman who lost most of her small bowel due to acute superior mesenteric thrombosis received a living-related small bowel transplant from her identical-twin sister. Monozygosity was established by buccal smear DNA amplification using short tandem repeat. A pretransplant panel-reactive antibody was 47.5% with several HLA antibodies in higher titers. The patient received a brief course of steroids without any additional immunosuppressive agents after transplantation. Her postoperative course was uneventful without an episode of rejection or infection. The preformed HLA antibodies steadily declined over time after transplantation. At a 5-year follow-up, the patient achieved full enteral autonomy from parenteral nutrition with a regular lifestyle. Conclusions. Identical-twin intestinal transplantation appears to provide the best outcomes by avoiding complications related to rejection and immunosuppression. We provide evidence that it may confer greater long-term immunological advantages even in a high-immunologic risk recipient.

Background. Every effort should be made to optimize surgical techniques and to minimize potential morbidity rates associated with live donor operations. Advances in a minimally invasive approach by robotic surgery to donor nephrectomy have raised the possibility of applying this technique to live donor bowel resections for intestinal transplantation. Methods. We report the first 5 consecutive cases of a robotic-assisted live donor ileal segmentectomy. We describe the technical aspects of the procedure, discuss the rationale for considering this option, and evaluate potential advantages of this approach. Results. We found that this new approach is associated with less postoperative discomfort, a shorter hospital length of stay, and a faster recovery of bowel function compared to our previous open surgery. Conclusions. Our initial experience suggests that robotic surgery is a safe and feasible procedure for live donor ileal resection for intestinal transplantation and is a useful alternative to conventional open surgery.

The effect of chemotherapy of gastric cancer (GC) remains very poor because of multidrug resistance (MDR). However, the mechanisms underlying MDR of GC remains far from fully understood. The aim of this study is to illustrate the potential mechanisms of the MDR of GC at mainly the long non-coding RNA (lncRNA) level. In this study, GC cell line, SGC7901, and two MDR sublines, SGC7901/VCR and SGC7901/ADR were subjected to an lncRNA microarray analysis. Bioinformatics and verification experiments were performed to investigate the potential lncRNAs involved in the development of MDR. Pathway analysis indicated that 15 pathways corresponded to down-regulated transcripts and that 20 pathways corresponded to up-regulated transcripts (p-value cut-off is 0.05). GO analysis showed that the highest enriched GOs targeted by up-regulated transcripts were "system development" and the highest esenriched GOs targeted by the down-regulated transcripts were "sterol biosynthetic process". Our study is the first to interrogate differentially expressed lncRNAs in human GC cell line and MDR sublines and indicates that lncRNAs are worthwhile for further study to be the novel candidate biomarkers for the clinical diagnosis of MDR and potential targets for further therapy.

As both major macronutrients and signal molecules, nitrogen metabolites, such as nitrate and nitrite, play an important role in plant growth and development. In this study, the callus growth of indica rice cv. 9311 was significantly enhanced by nitrite, whereas the soluble protein content remained unchanged. The deep RNA sequencing technology (RNA-seq) showed that the transcriptional profiles of cv. 9311 calli were significantly changed after adding nitrite to the nitrate-free medium, and these nitrite-responsive genes were involved in a wide range of plant processes, particularly in the secondary metabolite pathways. Interestingly, most of the genes involved in phenylpropanoid-related pathways were coordinately down-regulated by nitrite, such as four cinnamoyl-CoA reductase, and these in turn resulted in the decrease of lignin content of indica calli. Furthermore, several candidate genes related to cell growth or stress responses were identified, such as genes coding for expansins, SMALL AUXIN UP RNA (SAUR) and HSP20s, and these suggested that nitrite could probably serve as a transcriptome signal to enhance the indica calli growth by regulation of various downstream genes expression. This study contributes to a better understanding of the function of nitrite during the process of plant tissue culture and could aid in the application of this technology to improved indica genetic transformation efficiency.

MicroRNAs are noncoding RNAs that regulate multiple cellular processes during cancer progression. Among various microRNAs, MiR-630 has recently been identified to be implicated in many critical processes in human malignancies. We aimed to investigate the significance and prognostic value of miR-630 in human gastric cancer. Gastric cancer and adjacent normal specimens from 236 patients from who had not received neoadjuvant chemotherapy were collected. The expression of miR-630 was investigated by quantitative real-time PCR assay and its association with overall survival of patients was analyzed by statistical analysis. MiR-630 expression level was significantly elevated in gastric cancer in comparison to adjacent normal specimens. It is also proved that miR-630 expression was to be associated with gastric cancer invasion, lymph node metastasis, distant metastasis and TNM stage. In addition, survival analysis proved that elevated miR-630 expression was associated with poor overall survival of patients. Multivariate survival analysis also proved that miR-630 was an independent prognostic marker after adjusted for known prognostic factors. The present study proved the over-expression of miR-630 and its association with tumor progression in human gastric cancer. It also provided the first evidence that miR-630 expression was an independent prognostic factor for patients with gastric cancer, which might be a potential valuable biomarker for gastric cancer.

MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.