Factors Impacting One-year Follow-up Visit Adherence after Bariatric Surgery in West China: A Mixed Methods Study.

PURPOSE: Quality follow-up (FU) is crucial after bariatric surgery. However, poor adherence after surgery is prevalent. This research aimed to explore the factors related to FU adherence after bariatric surgery in West China. MATERIALS AND METHODS: This study used a sequential explanatory mixed-methods research design. Participants (n = 177) were identified from the West China Hospital. Demographic information, disease profile, treatment information, and post-surgery FU information were obtained from the bariatric surgery database of the Division of Gastrointestinal Surgery of the West China Hospital. The survey data were analyzed using logistic regression. Semi-structured interviews with participants (n = 10) who had low adherence were conducted. The recording was transcribed verbatim and entered into qualitative data analysis software. Qualitative data were analyzed using a content analysis approach. RESULTS: Multiple logistic regression revealed that living in Chengdu (OR, 2.308), being employed (OR, 2.532), non-smoking (OR, 2.805), and having less than five years of obesity (OR, 2.480) were positive predictors of FU adherence within one year. Semi-structured interviews suggested that factors related to adherence to FU were lack of motivation, lack of opportunity, insufficient ability, and beliefs regarding consequences. CONCLUSION: Factors impacting one-year FU visit adherence after bariatric surgery include not only demographic and disease-related factors but also social and family factors. These results will provide evidence to support healthcare professionals in developing personalized postoperative FU management strategies.

Bariatric surgery and health outcomes: An umbrella analysis.

Background: There is a relative lack of data that systematically investigates the breadth and validity of the association between bariatric surgery and health-related outcomes. We aimed to evaluate the quantity, validity, and credibility of evidence regarding the association between bariatric surgery and health-related outcomes using an umbrella review of meta-analyses. Methods: We systematically searched PubMed, Embase, and the Web of Science databases from inception until December 2, 2021, to identify meta-analyses of observational or interventional studies that investigated the association between bariatric surgery and multiple health outcomes. We extracted the summary effect size and 95% confidence interval (CI) data. The Assessment of Multiple Systematic Reviews (AMSTAR-2) and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines were used for methodological and evidence quality assessments, respectively. Results: Twenty-eight studies with 82 different health-related outcomes were included in this umbrella review. Beneficial effects of bariatric surgery have been observed in cancer incidence, mortality, cardiovascular risk, polycystic ovary syndrome (PCOS), anxiety symptoms, depressive symptoms, gestational diabetes mellitus, gestational hypertension, large for gestational age (LGA), macrosomia, post-term birth, risk of kidney stones, albuminuria, urinary incontinence, fecal incontinence, Barrett's esophagus, and diabetic retinopathy. However, adverse effects of bariatric surgery were observed for maternal anemia, perinatal mortality, congenital anomalies, preterm birth, neonatal intensive care unit (NICU) admission, intrauterine growth restriction, small for gestational age (SGA), fracture risk, upper limb fracture, suicide, self-harm, and alcohol use disorder (AUD). Conclusions: Current evidence suggests that bariatric surgery improves the majority of health-related outcomes; however, caution is advised given it may increase the risk of adverse mental effects, perinatal problems, and fractures.

Impact of Surgical Margin Status on Survival in Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: It is inconclusive whether R1 margin determined by postoperative pathological examination indicates worse long-term survival in gastric cancer (GC) patients after curative intent resection (CIR). Hence, we aimed to systematically pool the conflicting evidence to fill this gap. METHODS: The present study was performed according to the published protocol and Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Published studies examining the impact of microscopic margin status on overall survival (OS) and 5-year OS rate in GC were systematically searched in PubMed, Embase, and Cochrane Library databases. RevMan 5.3 was used to conduct statistical analysis, and the Grading of Recommendations, Assessment, Development, and Evaluations approach was used to assess the certainty of evidence for each outcome. RESULTS: Twenty-three retrospective cohort studies including 19 992 patients were analyzed. The pooled hazard ratio for OS of 14 studies was 2.06 (95% confidence interval [CI]: 1.61-2.65, low certainty), indicating that R1 margin predicted inferior OS. Subgroup and sensitivity analyses upheld the statistical stability of this finding. The pooled odds ratio (OR) of 14 studies was .21 (95% CI: .17-.26, moderate certainty), demonstrating that the presence of R1 margins was associated with a poorer 5-year OS rate. Sensitivity analyses and most of the subgroup analyses confirmed this finding, except the "esophagogastric junction (EGJ) cancers" subgroup, which included two studies with a pooled OR of .41 (95% CI: .10-1.61). CONCLUSION: R1 margin detected by pathological examination might exhibit a high correlation with poorer OS and 5-year OS rate in GC (except EGJ cancers) patients who underwent CIR. To figure out the effect of R1 margin on survival of different stages and histological types need prospective studies with large sample sizes and standardized methods. What is the best treatment for R1 margin patients also need more in-depth and special research.

Risk of falls in 4 years of follow-up among Chinese adults with diabetes: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVES: This study was to determine the incidence of falls and identify baseline factors increased risk for incident falls over time among people with diabetes. DESIGN: This study was a secondary analysis using the baseline and 4 years of follow-up data from the China Health and Retirement Longitudinal Study (CHARLS). SETTING: A nationally representative survey of 17 500 Chinese residents aged 45 years and older were recruited in the baseline national survey in 2011. These participants were followed up every 2 years. PARTICIPANTS: A total of 1238 middle-aged and older adults with diabetes and no history of falls at baseline were included in the current study. PRIMARY AND SECONDARY OUTCOME MEASURES: Information on incidence of falls and medical treatment resulting from falls were determined by self-report. RESULTS: The findings showed that the incidence of falls was 29.4% during 4 years of follow-up. Participants with incident falls were younger, were more likely to be women, had lower education level and were less likely to be current drinkers. In addition, former drinkers were 2.22 times more likely to fall. Socially active individuals were 47% less likely to fall compared with those without social activities. Every 5 kg increase in grip strength was associated with a 13% lower risk of falls. A 10 mg/dL higher total cholesterol and 1 mg/dL higher blood urea nitrogen were associated with a 4% and 6% higher risk of falls. Finally, participants with depressive symptoms were 1.47 times more likely to fall compared with those without depressive symptoms. CONCLUSIONS: These findings underscore the importance of developing a fall prevention programme for those with diabetes, and this programme should address potentially modifiable risk factors, including levels of total cholesterol, blood urea nitrogen, social activity, depressive symptoms and grip strength.

Adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in cancer patients: A systematic review and meta-analysis.

The efficacy of agents targeting epidermal growth factor receptor (EGFR) in patients with various cancers was well elucidated. However, the safety profile of EGFR tyrosine kinase inhibitors (EGFR-TKIs) has not been systematically investigated. This meta-analysis aimed to evaluate the safety profile of EGFR-TKIs in patients with cancer. A systematic search of PubMed, EMBASE, Cochrane Library databases, ASCO, and ESMO abstracts were conducted. Randomized controlled trials (RCTs) that compared safety profile of EGFR-TKIs with placebo were included. The end points included treatment-related adverse events (AEs), treatment discontinuation, and toxic death. Twenty-eight RCTs containing 17,800 patients were included. The analyses showed that the most frequently observed all-grade AEs in patients treated with EGFR-TKIs were diarrhea (53.7%), rash (48.6%), mucositis (46.5%), alanine aminotransferase (ALT) increased (38.9%), and skin reaction (35.2%). The most common high-grade (grade ≥3) AEs were mucositis (14.8%), pain (8.2%,), metabolism and nutrition disorders (7.4%), diarrhea (6.2%), dyspnea (6.1%), and hypertension (6.1%). The incidence of serious AEs, treatment discontinuation, and toxic death due to AEs were 18.2%, 12.36%, and 3.0%, respectively. Pooled risk ratio (RR) showed that the use of EGFR-TKIs was associated with an increased risk of developing AEs. Subgroup analysis indicated that the risk of AEs varied significantly according to tumor type, generation line, and drug type. Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique AEs. Early detection and proper management of AEs are important to reduce morbidity, avoid treatment discontinuation, and improve patient quality of life. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? The safety profile of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) varied in different trials, and has not been systemically investigated. WHAT QUESTION DID THIS STUDY ADDRESS? We conducted this meta-analysis of randomized control trials (RCTs) to provide a comprehensive evaluation of adverse event in patients with cancer receiving EGFR-TKIs. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Our meta-analysis indicates EGFR-TKIs was associated with a significant increased risk of a series of unique adverse events (AEs). HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The integrated understanding of safety profile of EGFR-TKIs will help in the future design of new EGFR-TKIs with a better safety profile.

Impact of surgical margin status on the survival outcome after surgical resection of gastric cancer: a protocol for systematic review and meta-analysis.

INTRODUCTION: Generally, complete resection with cancer cell negative (R0) margin has been accepted as the most effective treatment of gastric cancer and positive resection (R1/R2) margin has been associated with decreased survival to varied degrees. However, the independent impact of microscopical positive (R1) margin on long-term survival may be confounded. No meta-analysis has worked at the association between R1 margin and outcomes of gastric cancer and the available evidence are scant. Therefore, we plan to conduct a systematic review and meta-analysis to quantitatively explore the role of R1 margin on gastric (including oesophagogastric junction) cancer survival after curative intent resection. METHODS AND ANALYSIS: The protocol was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline. A systematic search of PubMed, Embase and the Cochrane Central Register of Controlled Trials databases will be performed from their inceptions to 30 April 2020 to identify randomised controlled trials (RCTs), cohort studies and case-control studies focusing on the impact of R1 margin on survival of gastric cancer after curative intent resection. The primary outcome will be the overall survival (OS) and disease-free survival (DFS) and the secondary outcomes will be 5-year OS rate and 5-year DFS rate. The Cochrane tool for bias assessment in randomised trials and Risk Of Bias In Non-randomised Studies-I for the assessment of bias in non-randomised studies (NRS) will be used. Statistical heterogeneity will be assessed by visual inspection of forest plots and measured using the I2 statistics. A fixed-effect model will be used when heterogeneity is low, otherwise, a random-effect model will be chosen. Publication bias will be assessed by funnel plots, subgroup analysis and sensitivity analysis will be performed in the right context. For each outcome, we will perform data synthesis separately for RCTs and NRS using Rev Man V.5.3 software and compile 'summary of findings' tables separately for RCTs and NRS using GRADEpro software. Grading of Recommendations, Assessment, Development and Evaluations considerations will also be used to make an overall assessment of the quality of evidence. ETHICS AND DISSEMINATION: There is no requirement for ethics approval because no patient data will be collected at an individual level in this systematic review and meta-analysis.The results of this systematic review will be published in a peer-reviewed journal and presented at relevant conferences, any deviations from the protocol will be clearly documented and explained in its final report. PROSPERO REGISTRATION NUMBER: CRD42020165110.

Incidence and risk factors of depressive symptoms in 4 years of follow-up among mid-aged and elderly community-dwelling Chinese adults: findings from the China Health and Retirement Longitudinal Study.

OBJECTIVES: The purpose of this study was to examine the incidence of depressive symptoms, and determine if baseline risk factors conferred a risk for incident depressive symptoms in nationally representative sample of mid-aged and elderly Chinese adults. DESIGN: This study was a secondary analysis of a prospective cohort from a nationally representative sample. SETTING: Community samples were recruited from the baseline survey of the China Health and Retirement Longitudinal Study. A four-stage, stratified, cluster probability sampling strategy was used, which included 10 257 households with members aged 45 years or older and their spouse. PARTICIPANTS: A total of 11 533 participants free of depressive symptoms at baseline were identified, and 10 288 were re-examined in either the first and/or the second follow-up surveys. The current analysis was conducted among the 10 288 participants. PRIMARY AND SECONDARY OUTCOME MEASURES: Depressive symptoms were measured by the Center for Epidemiological Studies Depression Scale short form. RESULTS: The findings showed that the incidence of depressive symptoms in a 4-year follow-up was as high as 22.3%. The incidence was much higher in rural areas (25.7%) and in women (27.9%). Furthermore, participants with 1 hour longer of night-time sleep had a 10% lower risk of developing depressive symptoms. Compared with individuals who perceived their health status as poor, those who perceived their health status as excellent had a 62% lower risk of developing depressive symptoms. In addition, having diabetes (OR=1.19), chronic kidney disease (OR=1.32), chronic digestive disorders (OR=1.15) and arthritis (OR=1.43) at baseline increased the risk of depressive symptoms. However, baseline body mass index was not associated with the subsequent depressive symptoms in this population. CONCLUSIONS: This study highlights the importance of developing an appropriate screening test to identify depressive symptoms for those who are vulnerable and ensure these individuals can receive early interventions for depressive symptoms.

Association between CT imaging features and KIT mutations in small intestinal gastrointestinal stromal tumors.

Small intestinal gastrointestinal stromal tumors (GISTs) have different clinical outcomes when KIT mutations are in exons 11 or 9, which are also the most common sites of neoplastic KIT mutations. The purpose of this study is to evaluate the CT imaging features in those two groups. A total of 35 patients were enrolled, and both quantitative and qualitative CT imaging features were compared between patient groups with KIT exon 9 mutations (KIT-9) and exon 11 mutations (KIT-11). The KIT-9 group was statistically associated with a tumor size larger than 10 cm and a higher enhancement ratio when compared with those of the KIT-11 group (both P < 0.05). For the enhancement ratio, the receiver operating characteristic curve indicated a cut-off value of 1.60 to differentiate KIT-9 from KIT-11 tumors. Additionally, tumor necrosis was more commonly seen in the KIT-9 group. In multivariate analysis, tumor size (ß = 0.206; P = 0.022) and KIT-9 (ß = 0.389; P = 0.006) were independent factors associated with tumor necrosis. Taken together, KIT-9 mutant tumors tended to have CT imaging features indicative of more aggressive neoplasms. These findings may be helpful in identifying more aggressive small intestinal GISTs and optimizing treatment.

Comparative Effectiveness of Neoadjuvant Treatments for Resectable Gastroesophageal Cancer: A Network Meta-Analysis.

Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.

Optimal reconstruction methods after distal gastrectomy for gastric cancer: A systematic review and network meta-analysis.

BACKGROUND: The choice of anastomosis methods including Billroth I, Billroth II, and Roux-en-Y after a distal gastrectomy is still controversial. The conventional meta-analyses assessing 2 alternative treatments were not powered to compare differences in clinical outcomes. To guide treatment decisions in patients with gastric cancer (GC) after distal gastrectomy, we did a systematic review and network meta-analysis to identify the best reconstruction method. METHODS: We systematically searched PubMed, EMBASE, the Cochrane Library for randomized controlled trials comparing the outcomes of Billroth I, Billroth II, or Roux-en-Y reconstruction after distal subtotal gastrectomy for patients with GC, then we performed a direct meta-analysis and Bayesian network meta-analysis to pooled odds ratios (OR) or weighted mean differences (WMD) with 95% credible intervals (CrI) with random effects model. The node-splitting method was used to assess the inconsistency. We estimated the potential ranking probability of treatments by calculating the surface under the cumulative ranking curve for each intervention. RESULTS: Nine studies involving 1161 patient were included in the network meta-analysis. Statistical significance was reached for the comparisons of Roux-en-Y versus Billroth I reconstruction (WMD 37, 95% Crl: 22-51) and Billroth II versus Billroth I reconstruction (WMD 25, 95% Crl: 5.8-43) for operation time; and Roux-en-Y versus Billroth I reconstruction (WMD 26, 95% Crl: 2.1-68) for intraoperative blood loss; and Roux-en-Y versus Billroth I reconstruction (OR 3.4, 95% Crl: 1.1-13) for delayed gastric emptying. Roux-en-Y reconstruction was superior to Billroth I and Billroth II reconstruction in terms of frequency of bile reflux (OR 0.095, 95% Crl: 0.010-0.63; OR 0.064, 95% Crl: 0.0037-0.84, respectively) and the incidence of remnant gastritis (OR 0.33, 95% Crl: 0.16-0.58; OR 0.40, 95% Crl: 0.17-0.92, respectively). CONCLUSION: Roux-en-Y reconstruction is superior to Billroth I and Billroth II reconstruction in terms of preventing bile reflux and remnant gastritis, Billroth I and Billroth II anastomosis could be considered as the substitute in consideration of technical simplicity. As for postoperative morbidity and the advantage of physiological food passage, Billroth I method is the choice.

Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis.

BACKGROUND: Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment. METHODS: We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS. RESULTS: 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63-0.89), (HR = 0.63 with 95% CrI: 0.52-0.76), and (HR = 0.66 with 95% CrI: 0.51-0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT. CONCLUSIONS: S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.

Prognoses in patients with primary gastrointestinal neuroendocrine neoplasms based on the proposed new classification scheme.

AIM: The aim of this study is to investigate the clinicopathological characteristics, as well as explore the prognostic accuracy of the proposed new classification in gastrointestinal NENs (GI-NENs) patients. METHODS: Patients diagnosed with GI-NENs were retrospectively indentified from existing databases of the pathological institute at our institution from January 2009 to November 2015. RESULTS: We identified 414 patients with GI-NENs, 250 cases were diagnosed as neuroendocrine tumor G1 (NET G1), 25 as neuroendocrine tumor G2 (NET G2), 53 as neuroendocrine tumor G3 (NET G3), 55 as neuroendocrine carcinoma G3 (NEC G3), and 31 as mixed adenoneuroendocrine carcinoma (MANEC); the overall survival (OS) rate at three years were 94.9%, 91.7%, 74.3%, 62.7% and 38.1%, respectively. The difference in progression-free survival (PFS) duration among the patients with NET G1, NET G2, NET G3, NEC G3, and MANEC was statistically significant (P < 0.001). However, the PFS of NEC G3 and MANEC was low and similar (P = 0.090). In multivariate analysis of patients with GI-NENs, surgical margin, comorbidity, proposed new classification and tumor location were useful predictors of OS (P < 0.05). CONCLUSION: Our findings suggest that the proposed new classification can accurately reflect the clinical outcome, together with surgical margin, comorbidity, and tumor location may be meaningful prognostic factors for the OS of GI-NENs.

Integrating multiple omics data for the discovery of potential Beclin-1 interactions in breast cancer.

Breast cancer has been reported as one of the most frequently diagnosed malignant diseases and the leading cause of cancer death in women all around the world. Furthermore, this complicated cancer is divided into multiple subtypes which present different clinical symptoms and need correspondingly directed therapy. We took BECN1, a core gene in autophagy performing a tumor inhibitory effect, as a starting point. The study in this paper aims to identify genes related to breast cancer and its multiple subtypes by integrating multiple omics data using the least absolute shrinkage and selection operator (LASSO), which is a statistical method that can integrate more than two types of omics data. All the data is obtained from The Cancer Genome Atlas (TCGA) platform which stores clinical and molecular tumor data. The model constructed is based on three kinds of data including mRNA-gene expression with a dependent variable level, DNA methylation and copy number alterations as independent variables. Finally, we propose four subnets of four subtypes of breast cancer, and consider as a result of microarray analysis that AFF3 is associated with BECN1 in breast cancer, and may be a potential therapeutic target. This finding may provide some potential targeted therapeutics for the four different subtypes of breast cancer at the genetic level. In conclusion, finding out the major role Beclin-1 plays in breast cancer subtypes is of great value. The results obtained are instructive for further research and may provide excellent results in clinical applications, as well as testing in animal experiments, and may also indicate a new method to perform bioinformatics analysis.

Characterization of HJ-PI01 as a novel Pim-2 inhibitor that induces apoptosis and autophagic cell death in triple-negative human breast cancer.

AIM: Pim-2 is a short-lived serine/threonine kinase, which plays a key role in metastasis of breast cancer through persistent activation of STAT3. Although the crystal structure of Pim-2 has been reported, but thus far no specific Pim-2-targeted compounds have been reported. In this study, we identified a novel Pim-2 inhibitor, HJ-PI01, by in silico analysis and experimental validation. METHODS: The protein-protein interaction (PPI) network, chemical synthesis, molecular docking, and molecular dynamics (MD) simulations were used to design and discover the new Pim-2 inhibitor HJ-PI01. The anti-tumor effects of HJ-PI01 were evaluated in human breast MDA-MB-231, MDA-MB-468, MDA-MB-436, MCF-7 cells in vitro and in MDA-MB-231 xenograft mice, which were treated with HJ-PI01 (40 mg·kg(-1)·d(-1), ig) with or without lienal polypeptide (50 mg·kg(-1)·d(-1), ip) for 10 d. The apoptosis/autophage-inducing mechanisms of HJ-PI01 were elucidated using Western blots, immunoblots, flow cytometry, transmission electron microscopy and fluorescence microscopy. RESULTS: Based on the PrePPI network, the potential partners interacting with Pim-2 in regulating apoptosis (160 protein pairs) and autophagy (47 protein pairs) were identified. Based on the structural characteristics of Pim-2, a total of 15 compounds (HJ-PI01 to HJ-P015) were synthesized, which showed moderate or remarkable anti-proliferative potency in the human breast cancer cell lines tested. The most effective compound HJ-PI01 exerted a robust inhibition on MDA-MB-231 cells compared with chlorpromazine and the pan-Pim inhibitor PI003. Molecular dynamics (MD) simulation revealed that HJ-PI01 had a good binding score with Pim-2. Moreover, HJ-PI01 (300 nmol/L) induced death receptor-dependent and mitochondrial apoptosis as well as autophagic death in MDA-MB-231 cells. In MDA-MB-231 xenograft mice, administration of HJ-PI01 remarkably inhibited the tumor growth and induced tumor cell apoptosis in vivo. Co-administration of HJ-PI01 with lienal polypeptide could improve the anti-tumor activity of HJ-PI01 and reduce its toxicity. CONCLUSION: The newly synthesized compound, HJ-PI01, can induce death receptor/mitochondrial apoptosis and autophagic cell death by targeting Pim-2 in human breast cancer cells in vitro and in vivo.

[Interleukin-10-1082 promoter polymorphism and the risk of gastric cancer].

OBJECTIVE: To investigate the association between Interleukin-10 (IL-10) promoter polymorphism and the gastric cancer risk in Chinese Han patients. METHODS: DNA was extracted from blood samples of gastric cancer patients (n = 75) and controls (n = 75). IL-10 -1082 promoter polymorphism in both patient and control group (three genotypes distribution: AA, AG and GG) was identified by PCR-RFLP and its relationship with gastric cancer risk, clinic and pathologic features was also analyzed. RESULTS: Patients with gastric cancer had a significantly lower frequency of AA (OR = 0.43, 95% CI = 0.20, 0.92; P = 0.03) than controls. Patients with proximal gastric cancer had a significantly higher frequency of GG (OR = 3.06, 95% CI = 1.12, 8.36; P = 0.03) than those with distant gastric cancer. Patients with advanced (stage II/IV) gastric cancer had a significantly higher frequency of AA (OR = 5.09, 95% CI = 1.05, 24.70; P = 0.04) than those with early (stage I /IV) gastric cancer. When stratified by the Lauren's classification, histological differentiation of gastric cancer, no statistically significant results was observed. CONCLUSION: This study suggests that the IL-1 1082 promoter polymorphism may be associated with gastric cancer in Chinese Han patients, and the difference in genotype distribution may be associated with the location and stage of gastric cancer.

Glutathione S-transferase M1 null genotype associated with gastric cancer among Asians.

PURPOSE: The Glutathione S-transferases (GSTs) play multiple roles in the pathogenesis and treatment of cancer. Studies investigating the association between Glutathione S-transferase M1 (GSTM1) null genotype and gastric cancer risk report conflicting results. The purpose of this study was to quantitatively summarize the evidence for such a relationship. RESULTS: This meta-analysis included 35 studies, which included 4,505 gastric cancer cases and 9,062 controls. The combined results based on all studies showed that the GSTM1 null genotype was associated with an increased risk of gastric cancer (OR = 1.15, 95% confidence interval [CI] = 1.02, 1.29). When stratifying for race, results were similar among Asians (OR = 1.24, 95% CI = 1.07, 1.44) except Caucasians (OR = 1.04, 95% CI = 0.88, 1.24). When stratifying by the location, stage, Lauren's classification, histological differentiation, lymph node metastasis, smoking, and Helicobacter pylori infection of gastric cancer, we observed that patients with diffuse classification had a significantly higher frequency null genotype (OR = 4.80, 95% CI = 1.65,13.94) than those with intestinal classification among Caucasians. CONCLUSIONS: This meta-analysis suggests that the GSTM1 null genotype may be associated with gastric cancer among Asians.

Glutathione S-transferase P1 gene polymorphism associated with gastric cancer among Caucasians.

Studies investigating the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and gastric cancer risk report conflicting results. The objective of this study was to quantitatively summarise the evidence for such a relationship. Two investigators independently searched the Medline and Embase databases. This meta-analysis included 10 case-control studies, which included 1161 gastric cancer cases and 2847 controls. The combined results based on all studies showed that there was no significant difference in genotype distribution [AA odds ratio (OR)=1.14, 95% confidence interval (CI)=0.91, 1.44; AG (OR=0.82, 95% CI=0.66, 1.03); GG (OR=1.11, 95% CI=0.55, 2.24)] between gastric cancer and non-cancer patients. When stratifying for race, results were similar except that patients with gastric cancer had a significantly higher frequency of AA (OR=1.53, 95% CI=1.14, 2.06) and lower frequency of AG (OR=0.70, 95% CI=0.55, 0.89) than non-cancer patients among Caucasians. When stratifying by the location and Lauren's classification of gastric cancer, we observed no statistically significant differences in genotype distribution. This meta-analysis suggests that the GSTP1 codon 105 polymorphism may be associated with gastric cancer among Caucasians.