Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Burden of gastroesophageal reflux disease in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of disease study 2019.

INTRODUCTION: For effective preventive strategies against GORD (gastro-esophageal reflux disease), we assessed the GORD burden from 1990 to 2019. METHODS: The burden of GORD between 1990 and 2019 was evaluated globally, regionally, and nationally. Using ASIR (age-standardized incidence), ASYLDs (age-standardized years lived with disabilitys), we compared them to the GBD world population per 100,000. The estimates were based on 95% uncertainty intervals (UIs). The AAPC (average annual percent change) in incidence, YLDs, along with prevalence rates with associated 95% CIs were estimated. RESULTS: Data to estimate the burden of GORD are scarce till now. The global ASIR of GORD in 2019 was 3792.79 per 100,000, an increase AAPC of 0.112% from 1990. The prevalence of GORD increased with a AAPC of 0.096% to 9574.45 per 100,000. Global ASYLDs in 2019 was 73.63, an increase AAPC of 0.105% from 1990. The GORD burden varies greatly depending on the development level and geographical location. USA demonstrated the most obvious decreasing trend in burden of GORD, while Sweden had an increasing trend. That the increase in GORD YLDs was mediated primarily by the growth and aging of population, was revealed by decomposition analyses. There was an inverse relationship between SDI (socio-demographic index) and GORD-burden. Frontier analyses revealed significant scope of improvement in the status of development at all levels. CONCLUSION: GORD is a public health challenge, especially in Latin America. Some SDI quintiles had declining rates, while some countries experienced increased rates. Thus, resources should be allocated for preventative measures based on country-specific estimates.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

A novel insight into the key gene signature associated with the immune landscape in the progression of sarcopenia.

Sarcopenia is an age-related skeletal muscle disorder that causes falls, disability and death in the elderly, but its exact mechanism remains unknown. In this study, we merged three GEO datasets into the expression profiles of 118 samples and screened 22 differentially expressed genes (DEGs) as candidate genes. Pathway analysis demonstrated that the functional enrichment of DEGs is mainly in the cellular response to insulin stimulus, PPAR signaling pathway and other metabolism-related pathways. Then, we identified six key genes by machine learning, which were confirmed to be closely associated with sarcopenia by bioinformatics analysis. It was experimentally verified that SCD1 exhibits the most substantial alterations in the progression of sarcopenia with disturbed lipid metabolism and myosteatosis. In addition, the immune microenvironment of sarcopenia was found to be affected by these key genes, with Th17 cells down-regulated and NK cells up-regulated. Sarcopenic patients consequently presented a more significant systemic inflammatory state with higher CAR (p = 0.028) and PAR (p = 0.018). For the first time, we identified key genes in sarcopenia with high-throughput data and demonstrated that key genes can regulate the progression of sarcopenia by affecting the immune microenvironment. Among them, SCD1 may influence lipid metabolism and myosteatosis process. Screening of key genes and analyzing of immune microenvironment provide a more accurate target for treating sarcopenia.

Thoracic sarcopenia predicts clinical outcomes in patients undergoing coronary artery bypass grafting: A 6-year cohort study.

BACKGROUND: The relationship between thoracic sarcopenia and clinical outcomes in patients underwent coronary artery bypass grafting (CABG) is unclear. This study aims to evaluate whether thoracic sarcopenia has a satisfactory prognostic effect on adverse outcomes after CABG. METHODS: From December 2015 to May 2021, 338 patients who underwent isolated CABG at our institution were recruited in this study. Skeletal muscle area at T12 level acquired by chest computed tomography (CT) was normalized to assess thoracic sarcopenia. Univariate and multivariate analyses were performed to evaluate the risk factors of postoperative complications and overall survival (OS). RESULTS: The prevalence of thoracic sarcopenia in patients underwent CABG was 13.02%. The incidence of total major complication was significantly higher in thoracic sarcopenia group (81.8% vs 61.9%, p = 0.010). Thoracic sarcopenic patients also had longer postoperative hospital stays (p = 0.047), intensive care unit (ICU) stays (p = 0.001), higher costs (p = 0.001) and readmission rates within 30 days of discharge (18.2% vs 4.4%, p = 0.001). Patients without thoracic sarcopenia showed significantly higher OS at the 2-year follow-up period (93.9% vs 72.7%, p<0.001). Multivariate analyses demonstrated that thoracic sarcopenia was significantly and independently associated with postoperative complications and long-term OS after CABG. CONCLUSION: Thoracic sarcopenia is an effective clinical predictor of adverse postoperative complications and long-term OS in patients underwent CABG. Thoracic sarcopenia based on chest CT should be included in preoperative risk assessment of CABG.

Prognostic significance of postoperative loss of skeletal muscle mass in patients underwent coronary artery bypass grafting.

Background: Increasing life expectancy of coronary artery bypass grafting (CABG) remains to be the major concern of cardiac surgeons. However, few studies have investigated the effect of postoperative skeletal muscle index (SMI) loss on prognosis. This study aims to evaluate the prognostic role of postoperative SMI loss ≥ 5% after CABG, in order to develop a novel nomogram to predict overall survival (OS). Methods: Patients underwent CABG via midline sternotomy from December 2015 to March 2021 were recruited in this study. Preoperative and postoperative 3 months chest computed tomography (CT) images were compared to assess changes in SMI at T12 level. Based on this, patients were classified into the presence or absence of SMI loss ≥ 5%. The association between postoperative SMI loss ≥ 5% and OS was then analyzed by the Kaplan-Meier curves and Cox model. A novel nomogram incorporating independent clinical prognostic variables was also developed. Results: The study enrolled 506 patients receiving CABG, of whom 98 patients experienced T12 SMI loss ≥ 5% and had a significantly worse OS (P < 0.0001). Multivariate regression analysis showed that T12 SMI per cent change (%T12 SMI-change) was an independent prognostic factor for OS (HR = 0.809, 95% CI = 0.749-0.874). The nomogram incorporating %T12 SMI-change with other variables was accurate for predicting OS. Besides, we also found that postoperative oral nutritional supplement (ONS) can rescue T12 SMI loss. Conclusion: Postoperative SMI loss can predict survival outcome after CABG. The nomogram incorporating changes in SMI provides a superior performance than existing systems.

Prognostic value of myosteatosis and sarcopenia for elderly patients with colorectal cancer: A large-scale double-center study.

BACKGROUND: Myosteatosis and sarcopenia are forms of muscle depletion that impair the normal physiological function of elderly patients, resulting in a worse prognosis. This study aimed to evaluate the prognostic value of sarcopenia and myosteatosis on postoperative outcomes in elderly patients with colorectal cancer. METHODS: From February 2015 to March 2021, a total of 921 elderly patients who underwent curative surgeries for colorectal cancer at 2 centers were enrolled and grouped by the presence of either myosteatosis or sarcopenia. Clinicopathological characteristics and postoperative outcomes were compared between the 2 groups. The independent risk factors for complications and overall survival were evaluated. RESULTS: Patients with myosteatosis had higher incidences of total and surgical complications, longer surgical duration, lower numbers of lymph nodes harvested, and longer postoperative hospital stays. Patients with sarcopenia had higher incidences of total complications, medical complications, and shorter surgical durations. Both conditions had adverse effects on overall survival and disease-free survival. Overweight status (P = .004), hypoalbuminemia (P < .001), myosteatosis, (P = .029) and sarcopenia (P = .017) were independent risk factors for total complications. Hypoalbuminemia (P = .035), myosteatosis (P = .003), sarcopenia (P = .027), and tumor-nodes-metastasis stage (≥Ⅲ; P < .001) were independent negative prognostic factors for overall survival. CONCLUSION: Myosteatosis and sarcopenia have different characteristics and are associated with poor prognoses in elderly patients with colorectal cancer. Myosteatosis occurs more frequently. Early diagnosis and intervention for myosteatosis should be included in preoperative management, which may improve prognosis in elderly patients.

Impact of sarcopenia on clinical outcomes of patients with stage I gastric cancer after radical gastrectomy: A prospective cohort study.

BACKGROUND: The relationships between sarcopenia and postoperative outcomes in patients with early-stage gastric cancer who undergo radical gastrectomy is unclear. We aimed to investigate the predictive value of sarcopenia on adverse outcomes for stage I gastric cancer. METHODS: The clinical data of patients who underwent radical gastrectomy for stage I gastric cancer between July 2013 and May 2019 were prospectively collected. Basic sarcopenia components were measured preoperatively. Univariate and multivariate analyses were conducted to evaluate the risk factors for short- and long-term outcomes. RESULTS: A total of 507 patients with early-stage gastric cancer were included in the study, and 73 (14.4%) patients were diagnosed as sarcopenia. Patients with sarcopenia had significantly higher incidence of postoperative complications (32.9% vs. 17.5%, P = 0.002), longer postoperative hospital stays (13 days vs. 12 days, P < 0.001), higher hospitalization costs (65210 yuan vs. 55197 yuan, P < 0.001) and one-year mortality (8.2% vs. 1.8%, P = 0.002). During the median follow-up time of 38.8 months, 12 (16.4%) patients dead in the sarcopenic group and 25 (5.8%) patients dead in the non-sarcopenic group. Sarcopenia was an independent risk factor for both short- and long-term clinical outcomes. Moreover, we found that low muscle quantity and low handgrip strength mediated the adverse impacts of sarcopenia on postoperative complications while low muscle quality mediated the adverse impacts of sarcopenia on overall survival. CONCLUSION: Sarcopenia was strongly associated with worse short- and long-term clinical outcomes in patients with stage I gastric cancer who undergo radical gastrectomy.

Sarcopenia is a predictive factor of poor quality of life and prognosis in patients after radical gastrectomy.

BACKGROUND: Patients with gastric cancer often suffer from generalized and progressive reduction of skeletal muscle mass and strength, which negatively affects the quality of life (QOL). In this study, we explored the impact of sarcopenia on QOL and overall survival (OS). METHODS: From December 2015 to June 2017, 135 patients underwent radical gastrectomy at the First Affiliated Hospital of Wenzhou Medical University. Based on the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS), data including handgrip strength, 6-m gait speed and muscle mass were collected and analyzed. EORTC QLQ-C30 and EORTC QLQ-STO22 were used to evaluate the QOL before surgery, 1, 3 and 6 months after surgery. RESULTS: A total of 27 out of the 135 patients (20.00%) were diagnosed with sarcopenia. Compared with non-sarcopenia group, patients in sarcopenia group had a higher incidence of postoperative complications (14.80% vs. 40.70%, p = 0.003), and more hospitalization costs (p = 0.029). The scores of eating restriction (p = 0.026), anxiety (p = 0.045) and body image (p = 0.046) were significantly higher in sarcopenia group at postoperative 6 months. Besides, sarcopenia was an independent risk factor for global health status at 6 months after operation (OR: 2.881, 95% CI: 1.110-7.475, p = 0.030) and OS (HR: 3.140, 95% CI: 1.255-7.855, p = 0.014). Other factors, including tumor stage III and the postoperative complications, had negative influences on OS. CONCLUSION: Sarcopenia is a predictive factor of poor QOL and prognosis in patients with gastric cancer.

Feasibility of substituting handgrip strength for muscle mass as a constituent standard in the Global Leadership Initiative on Malnutrition for diagnosing malnutrition in patients with gastrointestinal cancers.

OBJECTIVES: The aim of this study was to determine the feasibility of substituting handgrip strength (HGS) for muscle mass as a constituent in the Global Leadership Initiative on Malnutrition (GLIM) to diagnose malnourished patients with gastrointestinal (GI) cancer. METHODS: The study included 2209 patients diagnosed with GI cancer from two centers. All patients were evaluated for nutritional risk using Nutritional Risk Screening 2002 within 24 h of admission. The GLIM consensus was then used to diagnose malnourished patients. The evaluation of muscle mass as one of the constituents contained in the GLIM consensus was measured by computed tomography presented as skeletal muscle mass index (SMI) and HGS, respectively. Consistency test was carried out to evaluate the diagnostic value of SMI and HGS. RESULTS: There were 1042 (47.2%) cases of gastric cancer and 1167 (52.8%) cases of colorectal cancer. Among these cases were 768 patients (34.8%) at nutritional risk. Furthermore, 603 (27.3%) and 593 patients (26.8%) were diagnosed with malnutrition in the GLIM (SMI) group and the GLIM (HGS) group, respectively, and 544 (24.6%) patients in the two groups overlapped. The consistency test results showed that the κ value in the GLIM (HGS) group compared with the GLIM (SMI) group was 0.881 (P < 0.001) in patients with gastric cancer and 0.872 (P < 0.001) in those with colorectal cancer. CONCLUSION: HGS can be a substitute for muscle mass as a constituent in the diagnostic criteria of GLIM in patients with GI cancer.

Nrf2 deficiency promotes the increasing trend of autophagy during aging in skeletal muscle: a potential mechanism for the development of sarcopenia.

This study aims to explore the impact of nuclear factor erythroid 2-related factor 2 (Nrf2) deficiency on skeletal muscle autophagy and the development of sarcopenia. LC3b, P62, Bnip3, Lamp-1, and AMPK protein levels were measured in muscle from young, middle-aged, old Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice. Autophagy flux was measured in young WT, young KO, old WT, old KO mice, using colchicine as autophagy inhibitor. There was a trend of higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 induced by colchicine in old WT mice compared with young WT mice. Colchicine induced a significantly higher accumulation of LC3b-II, P62, Bnip3, Lamp-1 in KO mice compared with WT mice, both in the young and old groups. AMPK and reactive oxygen species (ROS) were unregulated following Nrf2 KO and increasing age, which was consistent with the increasing trend of autophagy flux following Nrf2 KO and increasing age. Nrf2 KO and increasing age caused decreased cross-sectional area of extensor digitorum longus and soleus muscles. We concluded that Nrf2 deficiency and increasing age may activate AMPK and ROS signals to cause excessive autophagy activation in skeletal muscle, which can be a potential mechanism for the development of sarcopenia.

Personalized four-category staging for predicting prognosis in patients with small bowel Adenocarcinoma: an international development and validation study.

BACKGROUND: Log odds of positive lymph nodes (LODDS) classification showed superiority over 8th edition N staging in predicting survival of small bowel adenocarcinoma (SBA) patients. The aim of this study was to develop and validate the Tumor, LODDS, and Metastasis (TLM) staging of SBA. METHODS: Totally 1789 SBA patients from the Surveillance, Epidemiology, and End Results (SEER) database between 1988-2010, 437 patients from SEER database between 2011-2013 and 166 patients from multicenters were categorized into development, validation and test cohort, respectively. The TLM staging was developed in the development cohort using Ensemble Algorithm for Clustering Cancer Data (EACCD) method. C-index was used to assess the performance of the TLM staging in predicting cancer-specific survival (CSS) and was compared with the traditional 8th edition TNM staging. FINDINGS: Four-category TLM staging designed for the development cohort showed higher discriminatory power than TNM staging in predicting CSS in the development cohort (0.682 vs. 0.650, P < 0.001), validation cohort (0.682 vs. 0.654, P = 0.022), and test cohort (0.659 vs. 0.611, P = 0.023), respectively. TLM staging continued to show its higher predictive efficacy than the 8th TNM in TNM stage II/III patients or in patients with lymph node yield less than 8. INTERPRETATION: TLM staging showed a better prognostic performance than the 8th TNM staging especially TNM stage II/III or patients with lymph node yield less than 8 and therefore, could serve to complement the TNM staging in patients with SBA. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Nrf2 deficiency exacerbates frailty and sarcopenia by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

AIM: Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process. METHODS: Young (5-6 months), middle-aged (11-13 months), old (20-24 months) Nrf2-/- (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology. RESULTS: Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle. CONCLUSION: Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner.

Additional lymphadenectomy might not improve survival of patients with resectable metastatic colorectal adenocarcinoma of T4 stage, proximal location, poor/undifferentiation, or N3/N4 stages: a large population-based study.

This study was performed to evaluate the prognostic effect of lymphadenectomy on outcomes in patients with resectable metastatic colorectal adenocarcinoma (mCRC). We selected patients with mCRC from 2004 to 2013 from Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan-Meier analysis, univariate Cox regression and multivariate Cox regression analysis were performed to assess the clinical value of lymphadenectomy on overall survival (OS) and cause-specific survival (CSS) of patients with resectable mCRC. A total 24178 eligible patients were included, 23056 (95.36%) of which received lymphadenectomy. Results showed that lymphadenectomy was an independent protective factor for survival of patients with mCRC overall [OS (HR: 0.86, 95%CI: 0.79-0.93, P=0.002) and CSS (HR: 0.85, 95%CI: 0.78-0.93, P<0.001)]. Further analysis showed that lymphadenectomy improved survival of patients with T1 stage [OS (HR: 0.51, 95%CI: 0.39-0.66, P<0.001); CSS (HR: 0.48, 95%CI: 0.36-0.65, P<0.001)], distal [OS (HR: 0.65, 95%CI: 0.56-0.75, P<0.001); CSS (HR: 0.65, 95%CI: 0.65-0.75, P<0.001)], rectal [OS (HR: 0.60, 95%CI: 0.52-0.70, P<0.001); CSS (HR: 0.59, 95%CI: 0.51-0.69, P<0.001)] , well/moderately differentiated [OS (HR: 0.62, 95%CI: 0.56-0.70, P<0.001); CSS (HR: 0.62, 95%CI: 0.55-0.69, P<0.001)], N1 stage [OS (HR: 0.76, 95%CI: 0.67-0.85, P<0.001); CSS (HR: 0.74, 95%CI: 0.65-0.84, P<0.001)] and N2 stage [OS (HR: 0.63, 95%CI: 0.54-0.74, P<0.001; CSS (HR: 0.65, 95%CI: 0.55-0.77, P<0.001)) mCRC. While lymphadenectomy might not improve survival of patients with T4 stage, proximal, poor or undifferentiated, N3 and N4 stage mCRC. In general, Additional lymphadenectomy was suggested for patients with mCRC overall. However, lymphadenectomy might not improve survival of patients with mCRC of higher malignancy tendency, such as T4 stage, proximal location, poor or undifferentiation, N3 and N4 stages.

Construction of eukaryotic expression vector of hypoxic inducible VEGF and its in vitro delivery application and functional identification / 解放军医学杂志

Objective To construct the eukaryotic expression vector of hypoxia inducible vascular endothelial growth factor (VEGF), and establish its in vitro delivery method. Methods Erythropoietin (EPO) enhancer was inserted into eukaryotic expression vector pGL4.73 [hRluc/SV40] (pSV) promoter by gene recombination technique to construct hypoxia inducible expression system (pEPO-SV). Renilla luciferase (Rluc) was used as downstream reporter gene. Then the VEGF165 gene was inserted into the pEPO-SV plasmid instead of Rluc, and the pEPO-SV-VEGF and pSV-VEGF expression vectors were obtained by inserting the pEPO-SV-VEGF gene into pSV as control. The pSV plasmid expressing Rluc or VEGF165 and pEPO-SV plasmid were transfected in vitro into human embryonic kidney 293T cells. The expression of Rluc or VEGF165 was used to identify the hypoxia induction function of the constructed vector after being treated under normal and hypoxic conditions for 24h and 48h. The intracellular delivery method of plasmids was then established based on poly (lactic acid-glycolic acid) copolymer (PLGA) nanoparticles as carrier, and the efficiency of the eukaryotic expression plasmids induced by hypoxia was evaluated under the in vitro hypoxia model. Results In the construction of plasmid, the successful insertion and correctness of EPO enhancer and VEGF165 gene were confirmed by restriction endonuclease digestion, PCR amplification and DNA sequencing. The plasmid expressing Rluc or VEGF165 was transfected into 293T cells respectively. There was no significant difference in the expression of reporter gene Rluc (one, plasmid pSV and pEPO-SV fluorescence expression values were 2448.24±158.51 and 3173.97±379.92, the second, plasmid pSV and pEPO-SV fluorescence expression values were 55 500.00±3237.05 and 51 193.18±866.32, respectively) or target gene VEGF165 in normal culture (P>0.05). But the expression of Rluc (In the cobalt chloride of hypoxia, the fluorescence expression values of pSV and pEPO-SV were 4857.70±1223.28 and 16 432.64±1618.73, respectively. In the hypoxia incubator, the fluorescence expression values of pSV and pEPO-SV were 2504.45±213.20 and 17 274.35±685.60, respectively) or VEGF165 in hypoxia was significantly higher than that in control group (P<0.01). The results showed that the constructed pEPO-SV and pEPO-SV-VEGF plasmids had typical hypoxia inducible expression activity. PLGA nanoparticles were used to in vitro deliver pEPO-SV and pSV in 293T cells. The results of detecting the reporter gene Rluc in normal culture and hypoxic conditions were consistent with those mentioned above, that is, under normal conditions, the 24h and 48h fluorescence expression values of plasmids pSV and pEPO-SV were 149.44±4.01 and 127.09±15.05, 1074.91±114.78 and 1064.56±137.48, respectively; under hypoxic conditions, the 24h and 48h fluorescence expression values of pSV and pEPO-SV were 3265.34±440.00 and 8828.87±637.03, 3202.06±33.43 and 9114.75±292.06, respectively. Conclusion A typical hypoxia inducible VEGF eukaryotic expression system has been successfully established, and an in vitro effective delivery method is also established, which may have an important application prospect in ischemia, hypoxia and other tissue injury diseases.

Situation of impaired glucose regulation and metabolic syndrome in overweight or obesity adolescent students in Dongguan city / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the occurrence and development of adolescent students' type 2 diabetes mellitus (T2DM) by researching the characteristics of the adolescent students' impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) effected by overweight or obesity.</p><p><b>METHODS</b>From May to November 2007, 3856 middle school students aged 11 to 18 years old in Dongguan city were enrolled in the study. Overweight or obesity (b/Ob) depended on three indexes: the national unified school-age children and adolescent students' body mass index (BMI) and the temporary screening classification standard II established by the Working Group on Obesity in China, BP > or = 140/90 mm Hg (1mm Hg = 0.133 kPa) and fasting capillary whole glucose which was greater than or equal to 5.6 mmol/L. The fasting capillary whole glucose was screened by blood glucose meter from fingertips. Students who had any abnormal indexes were brought into this study. On basis of voluntary principle, blood lipid, fasting blood glucose (FPG) and 2-hour postprandial blood glucose (2 h PG), fasting insulin (FIns) of 368 male and 326 female students who conformed to these conditions were measured using their venous blood. By temporary BMI standard II, they were divided into overweight group (b) and obesity group (Ob). Data of different age groups (11 to 14; 15 to 18 years old) was analyzed.</p><p><b>RESULTS</b>The BMI, low density lipoprotein cholesterol (LDL-C), insulin resistance index (IR), IFG and IGT of the same age stage in two groups were compared. The BMI value was (22.1 +/- 2.4) kg/m2, LDL-C was (2.38 +/- 0.65) mmol/L, IR was 1.15 +/- 0.58 and the detection rates of IFG and IGT were 3.5% and 1.4% respectively in female students aged 11 to 14 years old in b group. In Ob group, BMI value was (24.4 +/- 3.9) kg/m2, LDL-C was (2.70 +/- 0.73) mmol/L, IR was 1.36 +/- 0.67 and the detection rates of IFG and IGT were 14.6% and 6.3% respectively. t or chi2 values of two groups which were compared were 4.83, 2.45, 2.10, 7.41 and 7.99 (P < 0.01 or P < 0.05). BMI value was (25.8 +/- 3.1) kg/m2, LDL-C was (2.35 +/- 0.62) mmol/L, IR was 1.14 +/- 0.64 and the detection rates of IFG and IGT were 3.1% and 4.1% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.0 +/- 4.3) kg/m2, LDL-C was (2.69 +/- 0.69) mmol/L, IR was 1.43 +/- 0.84 and the detection rates of IFG and IGT were 12.8% and 15.4% respectively. t or chi2 values of two groups which were compared were 3.33, 2.79, 1.87, 4.75 and 5.17 (P < 0.01 or P < 0.05). BMI value was (22.4 +/- 2.3) kg/m2, LDL-C was (2.36 +/- 0.67) mmol/L, IR was 1.19 +/- 0.65 and the detection rates of IFG and IGT were 3.6% and 1.8% respectively in male students of 11 to 14 years old in b group. In Ob group, BMI value was (24.6 +/- 4.2) kg/m2, LDL-C was (2.68 +/- 0.71) mmol/L, IR was 1.44 +/- 0.89 and the detection rates of IFG and IGT were 13.3% and 9.4% respectively. t or chi2 values of two groups which were compared were 4.85, 2.72, 2.19, 6.75 and 6.76 (P < 0.01 or P < 0.05). BMI value was (26.4 +/- 2.8) kg/m2, LDL-C was (2.35 +/- 0.70) mmol/L, IR was 1.24 +/- 0.68 and the detection rates of IFG and IGT were 4.7% and 5.6% respectively in 15 to 18 years old in b group. In Ob group, BMI value was (28.2 +/- 4.8) kg/m2, LDL-C was (2.71 +/- 0.73) mmol/L, IR was 1.50 +/- 0.95 and the detection rates of IFG and IGT were 17.9% and 17.9% respectively. t or chi2 values of two groups which were compared were 2.80, 2.69, 1.84, 6.68 and 6.27 (P < 0.01 or P < 0.05). The male students' FPG of 11 to 14 years old in b group was (4.88 +/- 0.76) mmol/L and FPG of Ob group was (5.09 +/- 0.80) mmol/L. Two groups were compared and t = 1.84 (P < 0.05). The statistical differences were all observed. We compared different age stages and found that the male students' 2-hour PG of 11 to 14 years old in Ob group was (5.13 +/- 1.18) mmol/L and the 2-hour PG of 15 to 18 years old was (5.36 +/- 1.24) mmol/L. Two groups were compared and t = 1.78 (P < 0.05) near the adults value. Male students' IGT of 11 to 14 years old (b/Ob) had 8 positive cases and the positive detection rate was 3.6%. IGT of 15 to 18 years old (b/Ob) had 13 positive cases and the positive detection rate was 8.9%. Two age stages were compared and chi2 = 6.86 (P < 0.01). Female students' IGT of 11 to 14 years old (b/Ob) had 5 positive cases and the positive detection rate was 2.6%. IGT of 15 to 18 years old (b/Ob) had 10 positive cases and the positive detection rate was 7.4%. Two age stages were compared and chi2 = 4.02 (P < 0.05). All had statistical significance. The high IGT incidence rate of b/Ob group's male and female students was in the stage of 15 - 18 years old. Male students were more obvious.</p><p><b>CONCLUSION</b>T2DM prevention among adolescent students should start with body overweight control. Meanwhile, the adolescent students with high risk factors should be screened regularly and early measures should be taken to prevent the impaired glucose regulation (IFG, IGT) transforming into T2DM.</p>