Ginsenoside Rk1 attenuates radiation-induced intestinal injury through the PI3K/AKT/mTOR pathway.

Radiation-induced intestinal injury (RIII) frequently occurs during radiotherapy; however, methods for treating RIII are limited. Ginsenoside Rk1 (RK1) is a substance that is derived from ginseng, and it has several biological activities, such as antiapoptotic, antioxidant and anticancer activities. The present study was designed to investigate the potential protective effect of Rk1 on RIII and the potential mechanisms. The results showed that RK1 treatment significantly improved the survival rate of the irradiated rats and markedly ameliorated the structural injury of the intestinal mucosa observed by histology. Treatment with RK1 significantly alleviated radiation-induced intestinal epithelial cell oxidative stress apoptosis. Moreover, RNA-Seq identified 388 differentially expressed genes (DEGs) and showed that the PI3K-AKT pathway might be a key signaling pathway by which RK1 exerts its therapeutic effects on RIII. The western blotting results showed that the p-PI3K, p-AKT and p-mTOR expression levels, which were increased by radiation, were markedly inhibited by Rk1, and these effects were reversed by IGF-1. The present study demonstrates that Rk1 can alleviate RIII and that the mechanism underlying the antiapoptotic effects of RK1 may involve the suppression of the PI3K/Akt/mTOR pathway. This study provides a promising therapeutic agent for RIII.

Focus on Radiation Protection Improves Both Correct Behavior and Procedural Performance During Simulation-Based Training - A Randomized Comparison.

BACKGROUND: To explore whether simulation-based endovascular training with focus on radiation safety could improve correct behavior without jeopardizing the learning of procedural skills. METHODS: Twenty-four residents without previous endovascular experience completed 10 clinical scenarios on a virtual-reality endovascular simulator with software for peripheral endovascular interventions. Participants were randomized to receive feedback (n = 12) or not (n = 12) on radiation protection (RP) performance after each case. Expert assessments were done at the first, second, fourth, seventh, and 10th case on RP and endovascular skills (ES). Automatic simulator metrics on procedure time, contrast dose, handling errors, and estimated radiation exposure to patient and operator were registered. Outcome metrics were analyzed by two-way mixed analysis of variance pairwise comparisons with independent t-tests. Correlations were explored using Pearson's r for internal consistency reliability. RESULTS: The RP performance was similar in both groups at their first attempt (P = 0.61), but the feedback group significantly outperformed the control group over time (P < 0.001 for all comparisons). The feedback group was however slower to learn the ES at start (P = 0.047 at second performance), but after 7 attempts no difference was shown (P = 0.59). The feedback group used more time (19.5 vs. 15.3 min; P = 0.007) but less contrast (60 vs. 100 mL; P < 0.001). The number of errors was the same in both groups, but all metrics regarding radiation exposure favored the feedback group (P-values from 0.001 to 0.008). CONCLUSIONS: Simulation-based training (SBT) is effective to acquire basic endovascular intervention skills and concurrently learn RP behavior when feedback on radiation culture is provided.

Rectal NSAIDs in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis in unselected patients: Systematic review and meta-analysis.

BACKGROUND AND AIM: Efficacy of rectal non-steroidal anti-inflammatory drugs (NSAIDs) for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) prophylaxis in unselected patients remained controversial. The aim of the present study was to evaluate the efficacy of rectal NSAIDs in the prevention of PEP in unselected patients. METHODS: An electronic literature search in the Cochrane Library, Embase, and PubMed was carried out for randomized controlled trials comparing rectal indomethacin or diclofenac with placebo in the prevention of PEP in unselected patients. Cochrane risk of bias tool was used to evaluate methodological quality. The data were carried out in forest plots using fixed-effect methods, and random-effect methods were used when heterogeneity was significant. RESULTS: A total of nine trials were included in our final analysis. Rectal NSAIDs were effective to reduce the incidence of PEP in unselected patients (RR, 0.61; 95% CI, 0.46-0.79), especially for moderate-to-severe PEP (RR, 0.37; 95% CI, 0.17-0.79). Both indomethacin (RR, 0.67; 95% CI, 0.50-0.88) and diclofenac (RR, 0.29; 95% CI, 0.12-0.69) were significantly efficacious. Rectal NSAIDs given pre-ERCP showed significant efficacy (RR, 0.53; 95% CI, 0.39-0.71), whether when given within 30 min pre-ERCP (RR, 0.62; 95% CI, 0.42-0.92) or not (RR, 0.43; 95% CI, 0.28-0.67). CONCLUSION: Rectal NSAIDs are effective in the prevention of PEP in unselected patients.

Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study.

AIM: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. METHODS: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). RESULTS: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. CONCLUSIONS: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

Exploration of the molecular linkage between endometriosis and Crohn disease by bioinformatics methods.

BACKGROUND: Endometriosis (EMT) is a common disease in reproductive-age woman and Crohn disease (CD) is a chronic inflammatory disorder in gastrointestinal tract. Previous studies reported that patients with EMT had an increased risk of CD. However, the linkage between EMT and CD remains unclear. In this study, we aimed to investigate the potential molecular mechanism of EMT and CD. METHODS: The microarray data of EMT and CD were downloaded from Gene Expression Omnibus. Common genes of EMT and CD were obtained to perform the Gene Ontology and Kyoto Encyclopedia of Gene Genomes enrichments. The protein-protein interaction network was constructed by Cytoscape software and the hub genes were identified by CytoHubba plug-in. Finally we predicted the transcription factors (TFs) of hub genes and constructed a TFs-hub genes regulation network. RESULTS: A total of 50 common genes were identified. Kyoto Encyclopedia of Gene Genomes enrichment showed that the common genes mainly enriched in MAPK pathway, VEGF pathway, Wnt pathway, TGF-beta pathway, and Ras pathway. Fifteen hub genes were collected from the protein-protein interaction network, including FMOD, FRZB, CPE, SST, ISG15, EFEMP1, KDR, ADRA2A, FZD7, AQP1, IGFBP5, NAMPT, PLUA, FGF9, and FHL2. Among them, FGF9, FZD7, IGFBP5, KDR, and NAMPT were both validated in the other 2 datasets. Finally TFs-hub genes regulation network were constructed. CONCLUSION: Our findings firstly revealed the linkage between EMT and CD, including inflammation, angiogenesis, immune regulation, and cell behaviors, which may lead to the risk of CD in EMT. FGF9, FZD7, IGFBP5, KDR, and NAMPT may closely relate to the linkage.

Endoscopic sphincterotomy plus balloon dilation versus endoscopic sphincterotomy for choledocholithiasis: A meta-analysis.

BACKGROUND AND AIM: Endoscopic sphincterotomy (EST) alone and EST combined with balloon dilation (ESBD) are important endoscopic techniques for stone extraction. We were to conduct a meta-analysis to compare the efficacy and safety of ESBD and EST. METHODS: Meta-analysis was performed respectively on randomized controlled trials (RCTs) and nonrandomized studies comparing the efficacy and safety of ESBD and EST. RESULTS: The results of three RCTs showed that stone removal in first session (relative risk [RR] 1.01, 0.92-1.11, P=0.85) and the utility of endoscopic mechanical lithotripsy (EML) (RR 0.78, 0.49-1.23, P=0.29) were equivalent between ESBD and EST. ESBD has equivalent complications (RR 0.61, 0.17-2.25, P=0.46) and post-ERCP pancreatitis (Peto odds ratio [OR] 1.11, 0.37-3.35, P=0.86), but less bleeding (Peto OR 0.10, 0.03-0.30, P<0.0001). The analysis of six retrospective studies suggested higher initial success in stone removal (RR 1.11, 1.02-1.20, P=0.01) and less EML (RR 0.32, 0.22-0.46, P<0.00001) in ESBD group. Less complications (RR 0.60, 0.44-0.83, P=0.02) happened in ESBD group, but equivalent post-ERCP pancreatitis (Peto OR 0.65, 0.37-1.15, P=0.14) and bleeding (Peto OR 0.60, 0.29-1.26, P=0.18). For patients with stones ≥ 15 mm, ESBD required less EML (RR 0.35, 0.24-0.51, P<0.00001) and caused fewer complications (RR 0.67, 0.38-0.92, P=0.02). CONCLUSIONS: ESBD is feasible for the treatment of choledocholithiasis without increased risk of complications, causing less bleeding. However, it warrants more clinical trials to compare the efficacy and safety of ESBD and EST.

Water intubation method can reduce patients' pain and sedation rate in colonoscopy: a meta-analysis.

Several randomized controlled trials (RCT) have shown that water infusion in lieu of air insufflation reduces sedation rate and pain score and increases cecal intubation rate in colonoscopy. The aim of the present study was to confirm the beneficial effects of the water intubation method over the air method. Electronic databases were searched to identify RCT reporting colonoscopy detection using the water method. The pooled data of sedation rate, pain score and other procedure-related outcomes were analyzed. Then, 15 full-text articles were selected and assessed. Nine trials with high-quality scores were enrolled into this meta-analysis including a total of 1414 participants. Pooled odds ratio (OR) of sedation rate was 0.392 (95% confidence interval (CI): 0.288-0.533, P = 0.000). Pooled weighted mean difference (WMD) of pain score was -1.543 (95% CI: -2.107--1.069,P = 0.000). Pooled OR of cecal intubation rate was 1.90 (95% CI: 1.29-2.82, P = 0.001). Pooled OR of polyp detection rate and adenoma detection rate were 0.805 (95% CI: 0.606-1.069, P = 0.134) and 0.913 (95% CI: 0.681-1.223, P = 0.168), respectively. Pooled WMD of cecal intubation time was 0.701 (95% CI: -0.486-1.889, P = 0.247). This meta-analysis confirmed that the water method significantly reduced sedation rate and degree of pain without decreasing cecal intubation rate and disease detection rate and without requiring more cecal intubation time, suggesting that the novel water method is better than the conventional air method in colonoscopy detection.

Combination of vonoprazan and amoxicillin as the first-line Helicobacter pylori eradication therapy: a multicenter, prospective, randomized, parallel-controlled study.

The eradication rate of Helicobacter pylori (H. pylori) decreased gradually. This study aimed to analyze the efficacy and safety of a 14-day combination of vonoprazan and amoxicillin as the first-line eradication therapy for H. pylori infection and compared them with those of the bismuth quadruple therapy. A prospective randomized clinical trial (RCT) was designed, involving patients with H. pylori infection in 6 institutions who did not receive any treatment yet. They were randomly assigned into the VA-dual group (vonoprazan 20 mg b.i.d + amoxicillin 750 mg q.i.d) or EACP-quadruple group (esomeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg + colloidal bismuth subcitrate 220 mg b.i.d) for 14 days in a ratio of 1:1. At least 28 days later, the eradication rate was detected by the 13C-urea breath test (UBT). A total of 562 patients from February 2022 to September 2022 were enrolled and 316 were random. In the ITT analysis, the eradication rates of H. pylori in the VA-dual group and EACP-quadruple group were 89.9% and 81.0%, respectively, p = 0.037. In the PP analysis were 97.9% and 90.8%, p = 0.009. The different eradication rate was 8.9% (95% CI 1.2-16.5%) and 7.2% (95% CI 1.8-12.4%) in ITT and PP analyses, both lower limit of the 95%CI was still higher than the prespecified margin. In addition, the incidence of adverse events in the VA-dual group was significantly lower than that in the EACP-quadruple group (19.0% vs. 43.0%, P < 0.001). The efficacy and safety of a 14-day combination therapy of vonoprazan and amoxicillin in eradicating H. pylori are superior to bismuth quadruple therapy, and this combination significantly reduces the use of antibiotics.

Endoscopic papillary balloon dilatation versus endoscopic sphincterotomy in the treatment for choledocholithiasis: a meta-analysis.

BACKGROUND AND AIM: Endoscopic papillary balloon dilatation (EPBD) and endoscopic sphincterotomy (EST) are two common nonsurgical treatments endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. The aim of this study was to compare the efficacy and safety of EPBD and EST in the treatment for choledocholithiasis, confining the analysis to work reported in the last decade. METHODS: The rate of overall postoperative complications was chosen as the primary outcome, and 10 other outcomes were secondary outcomes. Relative risk (RR) or Peto odds ratio (OR) were computed as the measures of pooled effects. We planned sensitivity analyses a priori for examining the change in robustness of the sensitivity to excluding studies with some inappropriate objects, technique defects or without full-text acquisition. RESULTS: For complete stone removal, EPBD was similar to EST (95% vs. 96%, P = 0.36) and overall postoperative complications (14.0% vs. 11.7%, P = 0.53). The incidence of post-ERCP cholangitis (2.5% vs. 1.8%, P = 0.40), basket impaction (0.9% vs. 0%, P = 0.16) and perforation (0.0% vs. 0.4%, P = 0.17) were equivalent between EPBD and EST. On the other hand, EPBD caused more post-ERCP pancreatitis (PEP) (9.4% vs. 3.3%, P < 0.00001), but less hemorrhage (0.1% vs. 4.2%, P < 0.00001). People undergoing EPBD required more use of endoscopic mechanical lithotripsy (35.0% vs. 26.2%, P = 0.0004). The results of sensitivity analyses showed no substantial change. CONCLUSION: EPBD is comparable to EST for stone extraction, though it requires more endoscopic mechanical lithotripsy (EML). EPBD may outweigh EST for patients with coagulopathy; however, it may cause more PEP.

Association between inflammatory bowel disease and the risk of parenteral malignancies: A two-sample Mendelian randomization study

Abstract Aim: Using Mendelian Randomization (MR) analysis to investigate the potential causal association between Inflammatory Bowel Disease (IBD) and the occurrence of parenteral malignancies, in order to provide some reference for the parenteral malignancy prevention in patients with IBD. Methods: This was a two-sample MR study based on independent genetic variants strongly linked to IBD selected from the Genome-Wide Association Study (GWAS) meta-analysis carried out by the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). Parenteral malignancy cases and controls were obtained from the FinnGen consortium and the UK Biobank (UKB) release data. Inverse Variance Weighted (IVW), weighted median, MR-Egger, and strength test (F) were utilized to explore the causal association of IBD with parenteral malignancies. In addition, Cochran's Q statistic was performed to quantify the heterogeneity of Instrumental Variables (IVs). Results: The estimates of IVW showed that patients with IBD had higher odds of diffuse large B-cell lymphoma (OR = 1.2450, 95% CI: 1.0311‒1.5034). UC had potential causal associations with non-melanoma skin cancer (all p < 0.05), melanoma (OR = 1.0280, 95% CI: 0.9860‒1.0718), and skin cancer (OR = 1.0004, 95% CI: 1.0001‒1.0006). Also, having CD was associated with higher odds of non-melanoma skin cancer (all p < 0.05) and skin cancer (OR = 1.0287, 95% CI: 1.0022‒1.0559). In addition, results of pleiotropy and heterogeneity tests indicated these results are relatively robust. Conclusions: IBD has potential causal associations with diffuse large B-cell lymphoma and skin cancers, which may provide some information on the prevention of parenteral malignancies in patients with IBD. Moreover, further studies are needed to explore the specific mechanisms of the effect of IBD on skin cancers.

In vivo Imaging of a Novel Strain of Bacteroides fragilis via Metabolic Labeling.

Non-toxigenic Bacteroides fragilis is regarded as a potential candidate for probiotic owing to its various advantages. We previously isolated a new strain of B. fragilis (ZY-312) and verified its biosafety and capability of inhibiting the growth of pathogens in vivo. However, the colonization of ZY-312 in gastrointestinal (GI) tract remains to be determined. To track the colonization of ZY-312, mice were gavaged with ZY-312 labeled by means of metabolic oligosaccharide engineering and bioorthogonal click chemistry or given AF647-dibenzocyclooctyne (DIBO) directly. Then the fluorescence was detected in GI tract, spleen and kidneys. Results showed that ZY-312 could be labeled by metabolic oligosaccharide engineering, and the optimal incubation time with AF647-DIBO was 5 h in vitro. Following oral gavage with AF647-DIBO labeled ZY-312 or AF647-DIBO alone, mice were subjected to in vivo imaging and the fluorescence intensity was similar in both groups 3 h, 6 h, and 12 h post the gavage. The fluorescence of AF647-DIBO group disappeared 24 h post gavage which was probably due to the excretion via GI tract. While the fluorescence of AF647-DIBO labeled ZY-312 retained in the cecum for as long as 48 h. Immunofluorescence assay further confirmed that labeled ZY-312 transiently colonized not only in cecum but also in stomach, ileum and colon of mice 48 h post-gavage and that no massive accumulation of ZY-312 was detected in other organs such as kidneys and spleen. In conclusion, ZY-312 could transiently colonize in GI tract, mainly in cecum, for at least 48 h, and it hardly disseminate to other organs, which shed new light on the future development of B. fragilis as a probiotic product.

Effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality: A clinical observation study.

AIM: To evaluate the effects of hydrotalcite combined with esomeprazole on gastric ulcer healing quality. METHODS: Forty-eight patients diagnosed with gastric ulcer between June 2014 and February 2016 were randomly allocated to the combination therapy group or monotherapy group. The former received hydrotalcite combined with esomeprazole, and the latter received esomeprazole alone, for 8 wk. Twenty-four healthy volunteers were recruited and acted as the healthy control group. Endoscopic ulcer healing was observed using white light endoscopy and narrow band imaging magnifying endoscopy. The composition of collagen fibers, amount of collagen deposition, expression of factor VIII and TGF-ß1, and hydroxyproline content were analyzed by Masson staining, immunohistochemistry, immunofluorescent imaging and ELISA. RESULTS: Following treatment, changes in the gastric microvascular network were statistically different between the combination therapy group and the monotherapy group (P < 0.05). There were significant differences (P < 0.05) in collagen deposition, expression level of Factor VIII and TGF-ß1, and hydroxyproline content in the two treatment groups compared with the healthy control group. These parameters in the combination therapy group were significantly higher than in the monotherapy group (P < 0.05). The ratio of collagen I to collagen III was statistically different among the three groups, and was significantly higher in the combination therapy group than in the monotherapy group (P < 0.05). CONCLUSION: Hydrotalcite combined with esomeprazole is superior to esomeprazole alone in improving gastric ulcer healing quality in terms of improving microvascular morphology, degree of structure maturity and function of regenerated mucosa.

Effects of metformin on survival outcomes of pancreatic cancer: a meta-analysis.

BACKGROUND AND AIM: Recent epidemiological studies indicated that metformin might improve the survival of various cancers. However, its benefit on pancreatic cancer was controversial. METHODS: We performed this meta-analysis to investigate the benefit of metformin on pancreatic cancer. A comprehensive literature search was performed through PubMed, Cochrane Library and Embase. Relative risk (RR) and hazard ratio (HR) with 95% confidence interval (CI) were pooled. RESULTS: The meta-analysis of 2 randomized controlled trials including181 pancreatic patients, revealed that metformin use was not associated with an improved overall survival at 6 months (RR=0.90, 95% CI=0.67-1.21), overall survival (HR=1.19, 95% CI=0.86-1.63) and progression-free survival (HR=1.39, 95% CI=0.97-1.99). But the meta-analysis of 8 cohorts, involving 2805 pancreatic patients with diabetes, demonstrated a favorable result with improved overall survival (HR=0.78, 95% CI=0.66-0.92). CONCLUSIONS: Observations in the cohort studies supported a favorable role of metformin while the data from randomized controlled trials did not support that. Therefore, more high-quality RCTs are warranted.

Prognostic significance of neutrophil-to-lymphocyte ratio in rectal cancer: a meta-analysis.

BACKGROUND: Inflammatory responses play decisive roles in tumor development, immune surveillance, and responses to therapy. High neutrophil-to-lymphocyte ratio (NLR), as an inflammation index, has been reported to be a predictor for poor prognosis of various cancers. The purpose of this meta-analysis was to evaluate the prognostic value of NLR in patients with rectal cancer. METHODS: A comprehensive search of the literature was conducted through PubMed and EMBASE. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to evaluate the association between NLR and three outcomes: overall survival, disease-free survival, and recurrence-free survival. RESULTS: Seven cohorts involving 959 patients were included in this meta-analysis. Our pooled results demonstrated that elevated NLR was associated with poor overall survival (HR: 13.41, 95% CI: 4.90-36.72), disease-free survival (HR: 4.37, 95% CI: 2.33-8.19), and recurrence-free survival (HR: 3.64, 95% CI: 1.88-7.05). CONCLUSION: An elevated NLR is a valuable and easily available prognostic marker for rectal cancer. It is associated with unfavorable overall survival, disease-free survival, and recurrence-free survival. NLR could be a useful candidate factor for making treatment decisions for individual patients with rectal cancer.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. OBJECTIVE: We conducted this systematic review to assess the efficacy and safety of FMT in UC. DATA SOURCES: PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. DATA EXTRACTION AND SYNTHESIS: We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. RESULTS: Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. CONCLUSION: FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.

The role of PTEN in chronic growth hormone-induced hepatic insulin resistance.

Chronic growth hormone (GH) therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.