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Open abdominal surgery is frequently related to excessive inflammation and a compromised intestinal barrier, leading to poor clinical outcomes. The administration of beta-1 blocker has been shown to effectively reduce inflammation and preserve intestinal barrier function in patients with sepsis, shock, or other critical illnesses. The underlying mechanism of these effects may be associated with the autonomic nervous system's activation via cholecystokinin receptors. This study aimed to investigate the effect of beta-1 blocker on systemic and local inflammatory responses and the intestinal barrier function in the context of open abdominal surgery.A rat model of open abdominal surgery was induced through peritoneal air exposure for 3 hours and treated via gavage with the beta-1 blocker, metoprolol, or saline. Cholecystokinin-receptor antagonists were administered before the metoprolol treatment. Peritoneal lavage fluid, serum, and tissues were collected 24 hours after surgery to determine systemic and local inflammation and intestinal integrity.The intervention with metoprolol significantly reduced serum tumor necrosis factor-alpha and interleukin-6 (P.05) and peritoneal interleukin-6 (P.01) compared with those of animals treated with saline. The intestinal myeloperoxidase indicating the influx of neutrophils was also significantly prevented by the administration of metoprolol (P.05). Above all, this intervention resulted in a significant decrease in serum D-lactate and intestinal fatty acid-binding protein, intestinal permeability, bacterial translocation, and Chiu's score for intestinal mucosa injury (P.05). However, the anti-inflammatory and intestinal integrity protective effects of metoprolol were prevented by the blockage of cholecystokinin receptors (P.05).Our data indicate that beta-1 blocker reduces systemic and local inflammatory responses and preserves intestinal barrier function after open abdominal surgery through a mechanism that depends on cholecystokinin receptors. Clinically, these findings imply that perioperative intervention with a beta-1 blocker may be an effective new therapy to enhance recovery after open abdominal surgery.

Malnutrition characterized by the involuntary loss of body weight and skeletal muscle can be the result of both aging and malignancy. As a result, geriatric patients could face an increased nutritional risk. This study aimed to investigate the nutritional and functional status of geriatric patients and their association with postoperative complications.Patients who underwent abdominal surgery for digestive cancer in our center between January 2020 and August 2021 were included in the study. Computed tomography scans were collected to evaluate muscle mass and density. Changes in body weight, muscle strength, physical performances, nutritional risk, and status were evaluated upon admission. Postoperative outcomes collected included postoperative length of stay, complications, and 30-d readmission.A total of 1513 patients were included for the analysis. Of these, 72.8% were at risk for malnutrition (70.3% in the non-geriatric group and 75.4% in the geriatric group; P = 0.031), and 28.9% had malnutrition according to the Subjective Global Assessment (26.0% in the non-geriatric group and 31.8% in the geriatric group; P = 0.016). Compared with younger patients, geriatric patients have decreased muscle mass (skeletal muscle index, 44.8 versus 47.4; P0.001) and skeletal muscle density. Significant weight loss and loss of skeletal muscle occurred concurrently in 18.8% of the patients and were more frequent in the geriatric group (22.3% versus 14.7%; P0.001). In multivariate analysis, an age of 65 y or older (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.07-1.86; P = 0.014), a serum albumin level ≤4.11 g/dL (OR, 1.35; 95% CI, 1.03-1.77; P = 0.03), skeletal muscle loss (OR, 1.69; 95% CI, 1.28-2.24; P0.001), declined functional status (OR, 1.5; 95% CI, 1.14-1.98; P = 0.004), systematic inflammation (OR, 1.71; 95% CI, 1.09-2.8; P = 0.026), and significant weight loss (OR, 1.4; 95% CI, 1.06-2.85; P = 0.017) were independent predictors of overall postoperative complications. Although there was a trend of interactions between advanced age, skeletal muscle loss, and significant weight loss, multivariate analysis showed none of the interactions were significantly predictive of overall postoperative complications.Geriatric patients are at greater risk for malnutrition. Their declined nutritional and functional status together with advanced age could increase the risk for postoperative complications. Nutrition evaluation should be part of the preoperative workup, and timely interventions should be initiated if needed, especially in geriatric patients.

Summary Background & aims Malnutrition frequently occurs and deteriorates in patients after surgery for gastric cancer, especially after hospital discharge, which has been consistently associated with negative outcomes. However, information regarding the impact of post-discharge nutritional interventions is poorly described. The aim of this study was thus to evaluate the impact of post-discharge oral nutritional supplements (ONS) with dietary advice compared with dietary advice alone on nutritional outcomes, including body mass index (BMI) and skeletal muscle index (SMI), sarcopenia prevalence, chemotherapy tolerance, the 90-day readmission rate, and quality of life in patients at nutritional risk after surgery for gastric cancer. Methods Three hundred and fifty-three patients who underwent surgery for gastric cancer and were at nutritional risk (Nutritional Risk Screening 2002 [NRS 2002] score ≥3 points) in our institution were randomly assigned to receive either ONS with dietary advice or dietary advice alone (control) for 3 months after discharge. The primary endpoints were nutritional outcomes and sarcopenia prevalence; the secondary endpoints included chemotherapy tolerance, the 90-day readmission rate, and quality of life. Results Three hundred and thirty-seven patients completed the study and were included in the analyses, consisting of 171 in the ONS group and 166 in the control group. The average daily intake of ONS in the intervention group was 370 mL. After 3 months of the intervention, the patients who received ONS and dietary advice had significantly less weight loss and higher BMI and SMI than those given dietary advice alone (P 0.05). Regarding the quality of life, the patients who received ONS and dietary advice reported significantly less fatigue and appetite loss than those given dietary advice alone (P 0.05). Conclusions Post-discharge ONS with dietary advice in patients at nutritional risk after surgery for gastric cancer improved nutritional outcomes, skeletal muscle maintenance, chemotherapy tolerance and some quality of life variables. These findings strongly support the concept of the introduction of post-discharge ONS with dietary advice to this patient cohort.

Background: Loss of adipose tissue is one of the most important characteristics of cancer cachexia. The loss degree of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) is different in the same cachectic patient. However, it is unclear which genes lead to the differential fat loss in cancer cachexia. The purpose of this study is to screen the differentially expressed genes (DEGs) profile of SAT and VAT and clarify its function in cancer cachexia. Methods: We screened the DEGs of SAT and VAT in cachectic patients with gastric cancer by RNA sequencing. Gene enrichment analyses were preformed to analyze the biological function of DEGs. Interaction network was constructed to illustrate the relationship among key genes. Clinical significance of IRX1 related to cancer cachexia was illustrated by Spearman’s correlation analysis. SAT and VAT samples were collected and performed histomorphology analyses. Mouse model of cancer cachexia was established and differences between SAT and VAT were compared. The function of IRX1 on lipid metabolism was clarified by Oil Red O staining, qPCR, and western blotting in adipocytes. Results: A total of 455 DEGs were screened between SAT and VAT in cachectic patients with gastric cancer. Gene enrichment analysis indicated that the immune response might contribute to the pathological difference of SAT and VAT in caner cachexia. Patients with higher expression of IRX1 in SAT than VAT revealed significantly higher weight loss, IL-6 and TNFa concentration, as well as lower BMI, apoE, SAT and VAT area. A greater loss in SAT was observed in cachectic mice comparing to non-cachectic mice while the expression of IRX1 in SAT of cachectic mice was significantly higher. Oil Red O staining showed that IRX1 inhibited lipogenesis in adipocytes. Significant changes in the genes related to adipocyte differentiation and adipogenesis were observed in both the cases of IRX1 overexpression and knockdown. Conclusion: Higher expression of IRX1 was observed in SAT than VAT in gastric cancer patients with cachexia and thus IRX1 promotes loss of SAT by inhibiting adipocyte differentiation and adipogenesis. IRX1 is expected to be a potential target for the prevention and treatment of SAT loss in cancer cachexia.

BackgroundCancer-associated cachexia (CAC) is a syndrome characterized by skeletal muscle atrophy, and the underlying mechanisms are still unclear. Recent research studies have shed light on a noteworthy link between mitochondrial dynamics and muscle physiology. In the present study, we investigate the role of dynamin-related protein 1 (DRP1), a pivotal factor of mitochondrial dynamics, in myotube atrophy during cancer-associated cachexia.MethodsSeventy-six surgical patients, including gastrointestinal tumor and benign disease, were enrolled in the study and divided to three groups: control, non-cachexia, and cancer-associated cachexia. Demographic data were collected. Their rectus abdominis samples were acquired intraoperatively. Muscle fiber size, markers of ubiquitin proteasome system (UPS), mitochondrial ultrastructure, and markers of mitochondrial function and dynamics were assayed. A cachexia model in vitro was established via coculturing a C2C12 myotube with media from C26 colon cancer cells. A specific DRP1 inhibitor, Mdivi-1, and a lentivirus of DRP1 knockdown/overexpression were used to regulate the expression of DRP1. Muscle diameter, mitochondrial morphology, mass, reactive oxygen species (ROS), membrane potential, and markers of UPS, mitochondrial function, and dynamics were determined.ResultsPatients of cachexia suffered from a conspicuous worsened nutrition status and muscle loss compared to patients of other groups. Severe mitochondrial swelling and enlarged area were observed, and partial alterations in mitochondrial function were found in muscle. Analysis of mitochondrial dynamics indicated an upregulation of phosphorylated DRP1 at the ser616 site. In vitro, cancer media resulted in the atrophy of myotube. This was accompanied with a prominent unbalance of mitochondrial dynamics, as well as enhanced mitochondrial ROS and decreased mitochondrial function and membrane potential. However, certain concentrations of Mdivi-1 and DRP1 knockdown rebalanced the mitochondrial dynamics, mitigating this negative phenotype caused by cachexia. Moreover, overexpression of DRP1 aggravated these phenomena.ConclusionIn clinical patients, cachexia induces abnormal mitochondrial changes and possible fission activation for the atrophied muscle. Our cachexia model in vitro further demonstrates that unbalanced mitochondrial dynamics contributes to this atrophy and mitochondrial impairment, and rebuilding the balance by regulating of DRP1 could ameliorate these alterations.

Summary Background & aims Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. Design Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg–1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). Results MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min. Conclusion A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.

To investigate the levels of serum inflammatory cytokines and Resolvin D1 (RvD1) and their association with pathological staging of colon cancer.Clinical data of 50 colon cancer patients (colon cancer group) admitted to the General Surgery Department of Zhongshan Hospital of Fudan University from January to December 2016 and 5 ml of whole blood specimen were collected at admission. During the same period, 50 healthy volunteers were enrolled (healthy volunteer group). Inclusion criteria for the colon cancer group: colon cancer diagnosed by preoperative colonoscopy and pathology; no recent enteral or parenteral nutrition support treatment or use of oral nutrition preparation; age ≤85 years; no surgical contraindications by preoperative evaluation; no history of taking fish oil-related preparations; no radiotherapy or chemotherapy before surgery. Healthy volunteer group enrollment criteria: no history of malignant tumors; no organ with organic lesions detected by the healthy examination center of our hospital; detection indicators in normal reference range; no administration of fish oil-related preparations; age ≤ 85 years. Serum inflammatory factors(IL-1β, IL-6, IL-10 and TNF-α) concentrations were detected by chemiluminescence immunoassay; serum RvD1 concentration was measured by enzyme-linked immunosorbent assay. The levels of inflammatory factors and RvD1 were compared between the two groups, and their associations with TNM staging of colon cancer patients were analyzed.There were no significant differences in age, gender and nutrition-related indicators between the two groups (all P0.05). There were 31 males and 19 females in the healthy volunteer group with age of (61.8±11.6) years. There were 23 males and 27 females in the colon cancer group with age of (65.4±12.4) years. According to the 7th edition of the American Cancer Society TNM staging criteria, 10 cases were stage I, 13 cases stage II, 17 cases stage III, and 10 cases stage IV. Compared with healthy volunteer group, colon cancer group had higher serum IL-1β [(3.89±0.24)×10Compared with healthy volunteers, the levels of serum inflammatory cytokines in colon cancer patients increase significantly while the level of RvD1 decreases significantly. Both are associated with higher TNM stage of colon cancer.

Summary Background & aims Guidelines on clinical nutrition recommend the use of appropriate nutritional support therapy for surgical cancer patients at risk of malnutrition both during hospital care and following discharge from the hospital. However, previous studies regarding nutritional interventions have mainly focused on patients during their hospital stay; there is limited evidence supporting the recommendation of nutritional interventions for post-discharge patients after cancer surgery, particularly those who underwent gastrointestinal cancer surgery and at high risk of malnutrition. To clearly address this issue, we designed and conducted two independent studies on two different groups of post-discharge patients at nutritional risk after gastrointestinal cancer surgery. The present study aimed to assess the impact of oral nutritional supplements (ONS) in post-discharge patients at nutritional risk following colorectal cancer surgery. Meanwhile, the sister study on the use of ONS in post-discharge patients following gastric cancer surgery will be reported separately. Methods Between January 2017 and June 2019, post-discharge patients following colorectal cancer surgery in our institution were randomised to receive either dietary advice alone (control group) or dietary advice in combination with ONS (ONS group) for three months if they were at nutritional risk based on the tool of Nutritional Risk Screening 2002. The primary endpoints were nutritional outcomes and sarcopenia prevalence. The secondary endpoints were 90-day readmission rate, chemotherapy tolerance, and quality of life (QoL). Results Of the 232 eligible patients, 212 (107 in the control group and 105 in the ONS group) completed the trial. Their data were then analyzed. The mean ONS intake was 410 mL every day. By the three-month intervention, the skeletal muscle index in the ONS group was significantly higher than that in the control group (39.75 ± 5.83 vs 38.01 ± 6.18 cm2/m2, P = 0.037), but no significant differences between the two groups were noted in weight, weight loss, body mass index, serum albumin and hemoglobin (P > 0.05). In addition, the ONS group had a significantly lower sarcopenia prevalence (28.6% vs 42.1%, P = 0.040). No significant difference between the two groups was found in the 90-day readmission rate (P > 0.05). The number of patients undergoing postoperative chemotherapy in the two groups was similar, but chemotherapy modifications, such as delay, dose reduction, or termination, were significantly reduced in the ONS group (21.2% vs 36.8%, P=0.024). However, ONS had no significant effect on QoL (P > 0.05). Conclusions In post-discharge patients at nutritional risk following colorectal cancer surgery, the use of ONS may reduce skeletal muscle loss and sarcopenia prevalence, as well as improve chemotherapy tolerance, compared with dietary advice alone. These findings underline the importance of ONS treatment in post-discharge patients at nutritional risk following colorectal cancer surgery.

Hypoxia has been proved to be a typical character of solid tumors. Tumor cells prefer to use glucose through the glycolysis pathway instead of aerobic respiration. However, the precise molecular mechanism underlying this so-called Warburg effect remains elusive. In the current study, siRNA was synthesized and transfected into BxPC-3 cell line to silence the expression of HIF-1α gene. It was found that hypoxia induced hypoxia-inducible factor 1α (HIF-1α) overexpression in BxPC-3 cells, enhanced the expression of pyruvate dehydrogenase kinase 1 and lactate dehydrogenase A, thus facilitating glycolysis and making tumor cells more tolerant to hypoxic stress. The silencing of HIF-1α gene significantly attenuated glycolysis under hypoxic conditions, inhibited the growth and invasion ability of BxPC-3 cells, and enhanced hypoxia-induced cell apoptosis.

Chronic inflammation is a well-known etiological factor for colorectal cancer (CRC) and cancer cells are known to preferentially metabolize glucose through aerobic glycolysis. However, the connection between chronic inflammation and aerobic glycolysis in the development of CRC is largely unexplored. The present study investigated whether interleukin-6 (IL-6), a pro-inflammatory cytokine, promotes the development of CRC by regulating the aerobic glycolysis and the underlying molecular mechanisms. In colitis-associated CRC mouse, anti-IL-6 receptor antibody treatment reduced the incidence of CRC and decreased the expression of key genes in aerobic glycolysis, whereas the plasma concentrations of glucose and lactate were not affected. Consistently, IL-6 treatment stimulated aerobic glycolysis, upregulated key genes in aerobic glycolysis and promoted cell proliferation and migration in SW480 and SW1116 CRC cells. 6-phoshofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3) was the most downregulated gene by anti-IL-6 receptor antibody in colorectal adenoma tissues. Further analysis in human samples revealed overexpression of PFKFB3 in colorectal adenoma and adenocarcinoma tissues, which was also associated with lymph node metastasis, intravascular cancer embolus and TNM stage. In addition, the effect of IL-6 on CRC cells can be abolished by knocking down PRKFB3 through siRNA transfection. Our data suggest that chronic inflammation promotes the development of CRC by stimulating aerobic glycolysis and IL-6 is functioning, at least partly, through regulating PFKFB3 at early stage of CRC.

Summary Background & aims Sarcopenia has been widely recognized as an important predictor of poor outcomes in patients with cancer after surgery, but the controversy remains, and its impact on surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer is poorly described. The aim of this study was to evaluate the prognostic impact of sarcopenia on surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer. Methods Six thousand four hundred and forty-seven consecutive patients who underwent abdominal surgery for digestive tract cancer in our institution were prospectively included. Sarcopenia was defined as skeletal muscle index below the lowest sex-specific quartile using computed tomography scan at L3 before surgery. The surgical and oncologic outcomes were recorded, and univariate and multivariate analyses were performed. Results Sarcopenia was present in 1638 of 6447 patients (25.4%) with digestive tract cancer before surgery based on the diagnostic cut-off values (43.13 cm2/m2 for men and 37.81 cm2/m2 for women). The incidence of postoperative total and pulmonary complications, and 30-day readmission were significantly higher in sarcopenic group than in nonsarcopenic group (37.4% vs 12.9%, P Conclusions Sarcopenia could be used as a strong and independent prognostic factor for poor surgical and oncologic outcomes in patients after abdominal surgery for digestive tract cancer. Identification of preoperative sarcopenia in digestive surgery for cancer and targeted approaches may improve its negative outcomes.

A better understanding of breast cancer pathogenesis would contribute to improved diagnosis and therapy and potentially decreased mortality rates. Here, we found that the MORC family CW-type zinc finger 4 (MORC4) overexpression in breast cancer tissues is associated with poor survival, and the short-interfering RNA knockdown of MORC4 suppresses the growth of breast cancer cells by promoting apoptosis. To investigate the mechanisms associated with MORC4 upregulation, microRNAs potentially targeting MORC4 were analyzed, with miR-193b-3p identified as the regulator and a negative correlation between miR-193b-3p and MORC4 expression determined in both breast cancer cell lines and tissues. Further analysis verified that MORC4 silencing did not affect miR-193b-3p expression, although altered miR-193b-3p expression attenuated MORC4 protein levels. Moreover, dual-luciferase reporter assays verified miR-193b-3p binding to the 3' untranslated region of MORC4. Furthermore, restoration of miR-193b-3p expression in breast cancer cells led to decreased growth and activation of apoptosis, which was consistent with results associated with MORC4 silencing in breast cancer cells. These results identified MORC4 as differentially expressed in breast cancer cells and tissues and its downregulation by miR-193b-3p, as well as its roles in regulating the growth of breast cancer cells via regulation of apoptosis. Our findings offer novel insights into potential mechanisms associated with breast cancer pathogenesis.

Muscle atrophy F-Box (MAFbx)/atrogin-1 and muscle ring-finger-1 (MuRF-1) have been identified as two muscle-specific E3 ubiquitin ligases that are highly expressed in skeletal muscle during muscle atrophy. However, the role of muscle-specific E3 ubiquitin ligases during the process of muscle atrophy of cancer cachexia remains largely unknown. In the present study, we analyzed the expression of atrogin-1 and MuRF-1 in the skeletal muscle of patients with malignant and benign disease. The possible mechanisms were studied both in a colon 26-induced cancer cachexia mouse model and in tumor necrosis factor-alpha (TNF-alpha) induced atrophy C2C12 cells. Our results demonstrated that atrogin-1 and MuRF-1 tended to be increased in the skeletal muscle of patients with malignant disease even before weight loss. Non-tumor body weights and gastrocnemius weights were significantly decreased while expression levels of ubiquitin proteasome pathway associated genes (atrogin-1, MuRF-1, ubiquitin and E2-14K) were upregulated in cancer cachexia mice. Significant myotube atrophy with atrogin-1 overexpression was observed in the C2C12 cells treated with TNF-alpha. Meanwhile, knockdown of atrogin-1 by small interfering RNA (siRNA) protected C2C12 cells from the adverse effect of TNF-alpha. In conclusion, muscle-specific E3 ubiquitin ligases were upregulated during cancer cachexia, and atrogin-1 may be a potential molecular target for treating muscle atrophy induced by cancer cachexia.

Background: The prognostic value of human epidermal growth factor receptor-2 (HER-2/neu) for survival of patients with colorectal cancer (CRC) is still ambiguous. We therefore performed a meta-analysis to evaluate its prognostic significance. Materials and Methods: We searched the MEDLINE and EMBASE databases for published literature investigating associations between HER-2/neu status and overall survival of patients with CRC. A meta-analysis was performed using a DerSimonian-Laird model and publication bias was investigated by Begg’s and Egger’s tests. Subgroup analysis was also conducted according to the study design type, study quality score, cut-off value for HER-2/neu overexpression, publication region, patient number and publication year. Results: A total of 17 eligible studies involving 2,347 patients were identified for this meta-analysis. The combined hazard ratio (HR) was 1.31 (95% confidence interval (CI): 0.96-1.79), suggesting that HER-2/neu overexpression was not significantly associated with overall survival of patients with CRC. However, subgroup analysis revealed that HER-2/neu overexpression had an unfavorable impact on survival when the analysis was restricted to subgroups of study quality score ≤ 5 (HR=1.56, 95%CI: 1.17-2.10), Asian patients (HR=1.74, 95%CI: 1.22-2.49), patient number ≤ 106 (HR=1.57, 95%CI: 1.01-2.44), publication year before 2003 (HR=1.59, 95%CI: 1.02-2.49), and prospectively designed study (HR=3.62, 95%CI: 1.42-9.24). The effect disappeared in subgroups of study quality scores > 5 (HR=0.69, 95%CI: 0.33-1.44), non Asian patients (HR=1.14, 95%CI: 0.77-1.70), patients’ number > 106 (HR=1.07, 95%CI: 0.67-1.72), publication year after 2003 (HR=1.13, 95%CI: 0.76-1.69), and retrospectively designed study (HR=1.22, 95%CI: 0.89-1.67). Conclusions: Our meta-analysis suggests that HER-2/neu overexpression might not be a significantly prognostic indicator for patients with CRC. Further studies are required to confirm these results.

The role of laparoscopic surgery in the repair for peptic ulcer disease is unclear. The present study aimed to compare the safety and efficacy of laparoscopic versus open repair for peptic ulcer disease.Randomized controlled trials (RCTs) comparing laparoscopic versus open repair for peptic ulcer disease were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and references of identified articles and relevant reviews. Primary outcomes were postoperative complications, mortality, and reoperation. Secondary outcomes were operative time, postoperative pain, postoperative hospital stay, nasogastric tube duration, and time to resume diet. Statistical analysis was carried out by Review Manage software.Five RCTs investigating a total of 549 patients, of whom, 279 received laparoscopic repair and 270 received open repair, were included in the final analysis. There were no significant differences between these two procedures in some primary outcomes including overal postoperative complication rate, mortality, and reoperation rate. Subcategory analysis of postoperative complications showed that laparoscopic repair had also similar rates of repair site leakage, intra-abdominal abscess, postoperative ileus, pneumonia, and urinary tract infection as open surgery, except of the lower surgical site infection rate (P 0.05). In addition, there were also no significant differences between these two procedures in some second outcomes including operative time, postoperative hospital stay, and time to resume diet, but laparoscopic repair had shorter nasogastric tube duration (P 0.05) and less postoperative pain (P 0.05) than open surgery.Laparoscopic surgery is comparable with open surgery in the setting of repair for perforated peptic ulcer. The obvious advantages of laparoscopic surgery are the lower surgical site infection rate, shorter nasogastric tube duration and less postoperative pain. However, more higher quality studies should be undertaken to further assess the safety and efficacy of laparoscopic repair for peptic ulcer disease.

Pyruvate kinase type M2 (PKM2) has been reported to be involved in aerobic glycolysis and cell growth in various tumors. However, the expression pattern of PKM2 in colorectal cancer (CRC) and the correlation between PKM2 expression and CRC remains unclear. The aim of this study is to investigate PKM2 expression and its possible role in CRC. We found that expression of PKM2 was increased in CRC and the increased PKM2 expression was associated with later stage and lymph metastasis of the tumors. Knockdown of PKM2 suppressed the aerobic glycolysis and decreased lactate production of colon cancer RKO cells. Knockdown of PKM2 repressed proliferation and migration of the cells. Inhibition of PKM2 suppressed xenograft tumor growth of RKO cells in vivo. These results suggest that the expression of PKM2 plays a critical role in development of CRC, and it may provide a growth advantage for colon cancer cells. Thus, PKM2 might be a potential therapeutic target for CRC.

Objective To unravel the possible mechanism of acute posttraumatic insulin resistance in rats. Methods Resection of small intestine was performed to establish the surgical trauma model. The blood glucose and serum insulin level were detected and the HOMA index was calculated. The Hyperinsulinemic-euglycemic clamp was performed to investigate the glucose disposal rate by peripheral tissue. The content and phosphorylation state of IRS-1, p85 of PI3-K and PKB/Akt in skeletal muscle were measured respectively. Finally, the [3H] labeled glucose uptake experiment was carried out. Results The blood glucose elevated significantly after resection of small intestine in rats. The level of serum insulin decreased during the first 30 min after operation but elevated in the following time. The HOMA-IR in trauma group was significantly greater than control group; however the HOMA-β in trauma group was less than control group. The glucose disposal rate was decreased 49% after operation. The p-IRS-1(Ser307) was significantly enhanced 95% after trauma while the p-IRS-1 (Tyr612) was attenuated by 38%. The phosphorylation of its downstream target, p-PKB/Akt(Ser473) was attenuated by 48%. Accordingly, the glucose uptaken by skeletal muscle was significantly decreased in trauma group. Conclusion We demonstrated the posttraumatic insulin resistance occurred soon after surgical trauma in rats. The level of insulin was relatively insufficient because of the decreased sensitivity in peripheral tissue. Trauma induced Ser phosphorylation instead of Tyr phosphorylation eliminated the ability of IRS-1 to activate downstream effector molecules such as PKB/Akt and resulted in severe impairment of insulin signal transduction and glucose transport in skeletal muscle.

Interleukin-6 (IL-6) is a well-known etiological factor of colitis-associated colorectal cancer (CAC) and has a significant role in CAC progression. In addition, hypoxia-inducible factor 1α (HIF-1α) serves a primary role in the progression of CAC. However, the association between IL-6 and HIF-1α during the progression of CAC remains unclear. To investigate this association, the present study induced CAC in a mouse model using azoxymethane and dextran sulfate sodium. In addition, an anti-IL-6 receptor antibody was used to inhibit IL-6. In this model, anti-IL-6 receptor antibody treatment significantly inhibited the development of CAC and the expression of HIF-1α, in colorectal adenomas and adenocarcinomas. In patients with CAC, the HIF-1α gene was demonstrated to be overexpressed in tumor tissue compared with adjacent non-malignant tissue. Furthermore, HIF-1α mRNA expression was positively correlated with serum IL-6 concentration. The results of the present study suggest that IL-6 promotes CAC progression, in the early stage of the disease, through HIF-1α regulation.

Background and Objectives Consumption of dietary fat has been reported to be associated with gastric cancer risk, but the results of epidemiologic studies remain inconsistent. We conducted a meta-analysis to summarize the evidence regarding the association between dietary fat intake and gastric cancer risk. Methods A comprehensive search of PubMed and EMBASE was performed to identify observational studies providing quantitative estimates between dietary fat and gastric cancer risk. Random effects model was used to calculate the summary relative risk(SRR) in the highest versus lowest analysis. Categorical dose-response analysis was conducted to quantify the association between dietary fat intake and gastric cancer risk. Heterogeneity among studies was evaluated using I-2 and tau2(between study variance) statistics. Subgroup analysis and publication bias analysis were also performed. Results Twenty-two articles were included in the meta-analysis. The SRR for gastric cancer was 1.18 for individuals with highest intake versus lowest intake of total fat (95% confidence interval [CI]: 0.999-1.39; n = 28; P< 0.001; tau(2) = 0.12; I-2 = 69.5%, 95% CI: 55%-79%) and 1.08 with a daily increase in total fat intake (20 g/d) (95% CI: 1.02-1.14; n = 6; P = 0.09; tau(2) = 0.002; I-2 = 46.8%, 95% CI: 0%-79%). Positive association between saturated fat intake (SRR = 1.31; 95% CI: 1.09-1.58; n = 18; P

To investigate cachexia in hospitalized patients with digestive system cancer and evaluate its impact on clinical outcomes.By analyzing the clinical data of 5118 hospitalized patients with digestive system cancer in Zhongshan Hospital of Fudan University from January 2012 to December 2013, cachexia was investigated and clinical outcomes between cachexia patients and non-cachexia patients was compared.The total cachexia rate of hospitalized patients with digestive system cancer was 15.7%(803/5118). The highest rate of cachexia was 34.0%(89/262) in patients with pancreatic cancer followed by gastric cancer 22.4%(261/1164), colon cancer 21.7%(146/672), and rectal cancer 20.1%(117/581). In cachexia group and non-cachexia group, the overall completion rate of radical resection was 67.1%(539/803) and 74.5%(3214/4315) respectively(P0.05). Compared to the non-cachexia group, the cachexia group was associated with longer postoperative hospital stay [(11.5±6.2) d vs. (9.4±4.9) d, P0.05], slower postoperative recovery of bowel function [(3.4±0.9) d vs. (3.2±0.8) d, P0.05], longer postoperative time to intake of semifluid [(4.4±1.5) d vs. (3.9±1.1) d, P0.05], and more postoperative complications within 28 days after radical surgery [8.9%(48/539) vs. 5.8%(186/3214), P0.05]. After radical surgery, the ICU admission rate of the cachexia group [24.3%(131/539)] was higher than that of the non-cachexia group [20.1%(646/3214)] with significant difference(P0.05). Compared to non-cachexia group, the reoperation rate [3.2%(17/539) vs. 1.5%(48/3214), P0.05], ventilator support rate [8.0%(43/539)vs. 5.7%(184/3214), P0.05] and mortality [2.4%(13/539) vs. 1.1%(35/3214), P0.05] in the cachexia group were all significantly higher(all P0.05).Cachexia is commen in patients with digestive system cancer. Cachexia has significant adverse effects on clinical outcomes in hospitalized patients with digestive system cancer.

To evaluate the safety and short-term outcomes of laparoscopic-assisted surgery for rectal cancer by comparing the efficacy of laparoscopy and open surgery.Clinical data of patients with rectal cancer treated by laparoscopy or open surgery in Zhongshan Hospital from April 2011 to June 2012 were analyzed retrospectively, and the clinical outcomes between the two groups were compared.Ninety-six rectal cancer patients undergoing laparoscopic surgery(LS) were enrolled. A total of 216 rectal cancer patients underwent open surgery(OS). There was no operative death in both groups. In LS and OS group, the overall completion rates of TME were 86.4%(83/96) vs. 89.3%(193/216)(P0.05) respectively, and the overall anal reservation rates were 78.1%(75/96) vs. 75.0%(162/216)(P0.05) respectively. The mean distance to proximal resection margin and distal resection margin respectively were (10.3±4.1) cm vs.(10.0±4.3) cm(P0.05) and (3.4±0.9) cm vs. (3.6±1.4) cm(P0.05) respectively. The mean number of harvested lymph nodes respectively were (12.8±5.2) vs.(13.7±6.4)(P0.05). Compared to OS, LS presented less blood loss [(98.0±28.7) ml vs. (175.0±41.0) ml, P0.05], shorter postoperative hospital stay [(9.4±4.9) d vs.(11.6±6.2) d, P0.05], quicker postoperative recovery of bowel function[(2.7±0.9) d vs. (3.4±0.9) d, P0.05], shorter postoperative time to intake semi-solid[(3.7±1.2) d vs. (4.4±1.5) d, P0.05], less postoperative complications(15.6% vs. 25.9%, P0.05), but longer operative time[(155.7±48.4) min vs. (120.0±26.7) min, P0.05]. Postoperative follow-up was 6 to 24 months, and the local recurrence of LS and OS was 2.1% and 2.3%(P0.05).Laparoscopic surgery can obtain the same radical efficacy for rectal cancer as compared to open surgery.