Analysis of long-term outcome of modified gastric bypass for type 2 diabetes mellitus in Chinese patients.

BACKGROUND: Bariatric and metabolic surgery have been routinely performed following the rapid increase in obesity and metabolic diseases worldwide. Of all evolving procedures, Roux-en-Y gastric bypass (RYGB) is considered the gold standard for surgical treatment of patients with type 2 diabetes mellitus (T2DM) and obesity. RYGB was introduced in China nearly 20 years ago, but the number of RYGB surgeries only accounts for 3.1% of the total number of weight loss and metabolic surgeries in China, it's effect on Chinese people still needs further study. AIM: To investigate the effect and safety of a modified gastric bypass performed in Chinese patients with T2DM. METHODS: Patients with obesity and T2DM who underwent modified gastric bypass, with > 5-year follow-up data, were analyzed. RESULTS: All 37 patients underwent uneventful laparoscopic surgery, no patient was switched to laparotomy during the surgery, and no severe complications were reported. Average weight and body mass index of the patients reduced from 84.6 ± 17.3 (60.0-140.0) kg and 30.9 ± 5.0 (24.7-46.2) kg/m2 to 67.1 ± 12.2 (24.7-46.2) kg and 24.6 ± 3.9 (17.7-36.5) kg/m2, respectively, and fasting plasma glucose and glycated hemoglobin decreased from 7.4 ± 3.4 mmol/L and 8.2% ± 1.7% preoperatively to 6.5 ± 1.3 mmol/L and 6.5% ± 0.9% 5-years postoperatively, respectively. Only 29.7% (11/37) of the patients used hypoglycemic drugs 5-years postoperatively, and the complete remission rate of T2DM was 29.7% (11/37). Triglyceride level reduced significantly but high-density lipoprotein increased significantly (both P < 0.05) compared with those during the preoperative period. Liver and renal function improved significantly postoperatively, and binary logistic regression analysis revealed that the patients' preoperative history of T2DM and fasting C-peptide were significant prognostic factors influencing complete T2DM remission after RYGB (P = 0.006 and 0.012, respectively). CONCLUSION: The modified gastric bypass is a safe and feasible procedure for Chinese patients with obesity and T2DM, exhibiting satisfactory amelioration of weight problems, hyperglycemia, and combination disease.

Exploration of gene functions for esophageal squamous cell carcinoma using network-based guilt by association principle.

Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.

Exploration of gene functions for esophageal squamous cell carcinoma using network-based guilt by association principle

Gene networks have been broadly used to predict gene functions based on guilt by association (GBA) principle. Thus, in order to better understand the molecular mechanisms of esophageal squamous cell carcinoma (ESCC), our study was designed to use a network-based GBA method to identify the optimal gene functions for ESCC. To identify genomic bio-signatures for ESCC, microarray data of GSE20347 were first downloaded from a public functional genomics data repository of Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) between ESCC patients and controls were identified using the LIMMA method. Afterwards, construction of differential co-expression network (DCN) was performed relying on DEGs, followed by gene ontology (GO) enrichment analysis based on a known confirmed database and DEGs. Eventually, the optimal gene functions were predicted using GBA algorithm based on the area under the curve (AUC) for each GO term. Overall, 43 DEGs and 67 GO terms were gained for subsequent analysis. GBA predictions demonstrated that 13 GO functions with AUC>0.7 had a good classification ability. Significantly, 6 out of 13 GO terms yielded AUC>0.8, which were determined as the optimal gene functions. Interestingly, there were two GO categories with AUC>0.9, which included cell cycle checkpoint (AUC=0.91648), and mitotic sister chromatid segregation (AUC=0.91597). Our findings highlight the clinical implications of cell cycle checkpoint and mitotic sister chromatid segregation in ESCC progression and provide the molecular foundation for developing therapeutic targets.

Application of side-to-side anastomosis of the lesser curvature of stomach and jejunum in gastric bypass.

AIM: To evaluate the feasibility of side-to-side anastomosis of the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Seventy-seven patients received side-to-side anastomosis of the lesser curvature of stomach and jejunum by utilization of linear stapler in LRYGB from April 2012 to July 2015 were retrospectively analyzed. RESULTS: All patients were successfully completed laparoscopic gastric bypass with the side-to-side anastomosis of the lesser curvature of stomach and jejunum. No patient was switched to laparotomy during operation. No early complications including gastrointestinal anastomotic bleeding, fistula, obstruction, deep vein thrombosis, incision infections, intra-abdominal hernia complications were found. One patient complicated with stricture of gastrojejunal anastomosis (1.3%) and six patients complicated with incomplete intestinal obstruction (7.8%). BMI and HbA1c determined at 3, 6, 12, 24 mo during follow up period were significantly reduced compared with preoperative baselines respectively. The percentage of patients who maintain HbA1c (%) < 6.5% without taking antidiabetic drugs reached to 61.0%, 63.6%, 75.0%, and 63.6% respectively. The outcome parameters of concomitant diseases were significantly improved too. CONCLUSION: Present surgery is a safety and feasibility procedure. It is effective to lighten the body weight of patients and improve type 2 diabetes and related complications.

Near-UV-enhanced broad-band large third-order optical nonlinearity in aluminum nanorod array film with sub-10 nm gaps.

Plasmonic nanostructures with sub-10 nm gaps possess intense electric field enhancements, leading to their high reputation for exploring various functional applications at nanoscale. Till now, although large amounts of efforts have been devoted into investigation of such structures, few works were emphased on the nonlinear optical properties in near-ultraviolet (UV) region. Here, by combining sputtering technique and an optimized anodic aluminum oxide (AAO) template growing method, we obtain aluminum (Al) nanorod array film (NRAF) with average rod diameter and gap size of 50 and 7 nm, respectively. The Al-NRAF exhibits large third-order optical nonlinear susceptibility (χ(3)) and high figure of merit (χ(3)/α) over a broad wavelength range from 360 to 900 nm, and reaches their maximums at the shortest measured wavelength. In addition, comparisons with Au-NRAF and Ag-NRAF samples further confirm that Al-NRAF has better nonlinear optical properties in the blue and near-UV wavelength regions. These results indicate that Al nanostructures are promising candidates for nonlinear plasmonic applications at blue and near-UV wavelengths.

[Analysis of scatter plots and alarm information in 288 cases of newly diagnosed hematologic malignancies].

This study was aimed to explore the role of full-automatic blood analyzer Sysmex XE-2100 in early screening and diagnosing the hematologic malignancies. A total of 288 samples of the patients with hematologic malignancies was examined. Then, the scatter plots, alarm information and blood smears were analyzed. The results indicated that 76% of these samples showed abnormal scatter plots. CMML and AML-M3 patients had their own characteristic scatter plots, while others hadnt's. The coincident rate of CMML and AML-M3 determined by scatter plots with practical diseases was 100%; the coincident rate of ALL determined by scatter plots with practical disease was 67%. The coincident rate of alarm information of blast cells was 92.5%, the coincident rate of immature granulocytes was 77.1%, the coincident rate of nucleated red blood cells was 33.3%, the coincident rate of atypical lymphocytes was 31.3%. It is concluded that the abnormal scatter plots and alarm information are very important for finding the patients with hematologic malignancies and determining the disease type. The alarm information has high reliability for blast cells and immature granulocytes, but has only mirror value for nucleated red blood cells and atypical lymphocytes.

[The effects of gastric bypass procedures on blood glucose, gastric inhibitory polypeptide and glucagon-like peptide-1 of normal glucose tolerance dogs].

OBJECTIVE: To observe postoperative glucose tolerance, gastric inhibitory polypeptide (GIP) , and glucogan-like peptide-1 (GLP-1) in normal glucose level dogs after undergoing gastric bypass procedures, and to explore the mechanism of gastric bypass procedures to treat type 2 diabetes. METHODS: The 6 dogs with normal glucose tolerance had undergone gastric bypass procedures, and measure preoperative and postoperative oral and intravenous glucose tolerance (at time points 1, 2, and 4 weeks) through changes in blood glucose, insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and measure preoperative and postoperative week 4 pancreatic tissue morphology. RESULTS: Second weeks after operation, the fasting blood sugar was (3.58 ± 0.33) mmol/L, and significantly lower than preoperative (t = 3.571, P < 0.05). The GLP-1 level before oral glucose tolerance test (OGTT) and 30 minutes after OGTT were (0.90 ± 0.21) and (0.91 ± 0.19) pmol/L respectively, and significantly higher than preoperative (t value were -3.660 and -2.971, P < 0.05). GLP-1 levels began to decrease in the second week after surgery. After 4 weeks, the index recovered to the preoperative level. Four weeks after surgery when compared with preoperative, islet morphology, islet number (6.8 ± 0.8 and 7.1 ± 0.8 respectively) and islet cells (16.7 ± 2.5 and 16.3 ± 3.1 respectively) did not change significantly (P > 0.05). CONCLUSION: Gastric bypass procedures could be briefly affect normal glucose tolerance in dogs' blood glucose, insulin and diabetes-related gastrointestinal hormones.

[Application of side to side anastomosis between the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass].

OBJECTIVE: To evaluate the application of side-to-side anastomosis of the lesser curvature of stomach and jejunum in laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Clinical data of 29 patients with type 2 diabetes mellitus (T2DM) undergoing side to side anastomosis of the lesser curvature of stomach and jejunum in LRYGB from May 2012 to November 2012 in Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University were analyzed retrospectively. RESULTS: All the procedures were successfully completed without conversion to laparotomy. The side-to-side anastomosis of the lesser curvature of stomach and jejunum avoided the laparoscopic suture. No gastrojejunostomy anastomotic bleeding, fistula, obstruction and other complications occurred after operation and no complications of gastrojejunostomy anastomosis were found during a follow up of 1 to 7 months. CONCLUSIONS: Side-to-side anastomosis of the lesser curvature of stomach and jejunum in LRYGB can manipulate the size of anastomosis accurately and avoid the laparoscopic suturing. It is simple and easy to learn.

Knockdown of Ezrin by RNA interference reverses malignant behavior of human pancreatic cancer cells in vitro.

BACKGROUND: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. METHODS: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. RESULTS: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). CONCLUSIONS: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

Knockdown of radixin by RNA interference suppresses the growth of human pancreatic cancer cells in vitro and in vivo.

Radixin, encoded by a gene on chromosome 11, plays important roles in cell motility, invasion and tumor progression. However, its function in pancreatic cancer remains elusive. In this study, radixin gene expression was suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method. We found that radixin shRNA caused down-regulation of radixin in PANC-1 cells, associated with inhibition of pancreatic cancer cell proliferation, survival, adhesion and invasive potential in vitro. When radixin-silenced cells were implanted in nude mice, tumor growth and microvessel density were significantly inhibited as compared to blank control cells or nonsense shRNA control cells. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin-silenced PANC-1 cells. Our results suggest that radixin might play a critical role in pancreatic cancer progression, possibly through involvement of down-regulation of TSP-1 and E-cadherin expression.

[Rhodiola sachalinensis suppresses T241 fibrosarcoma tumor cells proliferation in vitro and growth in vivo].

OBJECTIVE: To study the anticancer activity of Rhodiola sachalinensis in vitro and in vivo experiments. METHODS: The effect of Rhodiola sachalinensis extracts at various concentrations on T241 fibrosarcoma cells proliferation and cytotoxic potential were measured. We divided T241 fibrosarcoma-bearing C57Bl6/J mice into two groups, the tumor inhibition rate were observed. RESULTS: Rhodiola sachalinensis extracts inhibited T241 tumor cells growth in a dose-dependent manner. The concentrations of Rhodiola sachalinensis extracts from 50 microg/ml to 250 microg/ml did not reduced the survival rate of T241 tumor cells. The daily administration of Rhodiola sachalinensis resulted in a significant suppression of the growth of primary tumors, compared to control group, tumor inhibition rate in Rhodiola sachalinensis group reached 70.9%. CONCLUSION: Rhodiola sachalinensis can inhibit T241 tumor cells growth and does not cause a direct cytotoxicity against tumor cells in vitro and in vivo.

[Ganoderma spores may regulate the levels of mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension].

OBJECTIVE: To investigate the effects of Ganoderma spores on mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension. METHODS: Nitric oxide synthase (NOS) inhibitor Nw-nitro-L-arginine methylester (L-NAME) was intraperitoneally injected into pregnant rats to induce gestational hypertension, and Ganoderma spores were administered orally. The effects of Ganoderma spores on levels of mitochondria-related molecular substances in hippocampus of young rats birthed by the rats with gestational hypertension were evaluated with immunoradiometric assay of cAMP, RT-PCR analysis of related genes, and detection of enzyme activity. RESULTS: In hippocampus of the new-born rats birthed by rats with gestational hypertension, the cAMP level, mitochondrial DNA (mtDNA) level and adenosine triphosphatase (ATPase) activity were decreased, and the expression level of peroxisome proliferator activated receptor gamma coactivator 1 alpha (pgc1 alpha) was unchanged compared to the normal control group. The cAMP level, mtDNA level, ATPase activity and pgc1 alpha expression level in hippocampus of 30-day post-natal rats were lower than those of the rats in normal control group. After oral administration of Ganoderma spores, the cAMP and mtDNA levels in hippocampus of the new-born rats and 30-day post-natal rats recovered almost to the levels of normal control rats, and the ATPase activity and pgc1 alpha expression level were also increased significantly. CONCLUSION: Ganoderma spores may regulate the levels of mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension.

[Pre-administration of Ganoderma lucidum spore reduces incidence of neural tube defects induced by retinoic acid in pregnant mice].

OBJECTIVE: To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. METHODS: Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. RESULTS: The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. CONCLUSION: Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.