Calculated cancer risks for polycyclic aromatic hydrocarbon mixtures in mainstream smoke of cigarettes sold in China.

China is the world's largest consumer of cigarettes. However, the potential cancer risk posed by polycyclic aromatic hydrocarbons (PAHs) in mainstream cigarette smoke, especially species other than benzo[a]pyrene (BaP) remains unclear. In this study, we collected yield data on multiple PAH species from a variety of cigarettes in the China market and calculated their smoking-related incremental lifetime cancer risk (ILCR) values. The computed ILCRs of the total PAHs (ILCRΣPAHs) for ≥95% of the brands were one order of magnitude higher than the acceptable level. ILCRBaP accounted for only 5.0%-37.7% of ILCRΣPAHs among brands, indicating that using single analyte BaP to represent ΣPAHs would significantly underestimate ILCRΣPAHs. No clear trend of changes in ILCRΣPAHs was found for Chinese cigarettes over multiple years, suggesting that smoking cessation is still the best option to minimize the cancer risk of PAHs. The comparison study showed that rarely reported PAHs from Chinese cigarettes can contribute over half of ILCRΣPAHs for several American cigarettes, highlighting the imperativeness to improve the diversity of analytes for Chinese cigarettes. Adults would need to inhale the air-borne PAHs with a BaP equivalent concentration of at least 53.1 ng/m3 to reach the ILCR value comparable to that obtained from smoking.

The PER3rs772027021 SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria.

Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. Although Sterile Alpha motif- and SH3 domain-containing protein 1 (SASH1) and ATP-binding cassette subfamily B, member 6 (ABCB6) have been identified as causative genes for this disorder, some cases involve unknown pathogenic genes. In this study, whole-exome sequencing, data analysis, and Sanger sequencing were utilized for a four-generation extended Chinese family with DUH. A single-nucleotide polymorphism (SNP) (c. 517C > T (p.P173S), rs772027021) variant in exon 5 of Period Circadian Regulator 3 (PER3) (NM_001289861) was detected in each affected individual of the DUH family; the c. 517C > T SNP of PER3 (PER3rs772027021 SNP) and a novel mutation in exon 14 of SASH1 (c. 1574C > G (p.T525R)) were both found in the proband. The affected individuals carrying PER3rs772027021 SNP in this family demonstrated mild-pigmented phenotypes compared to those of the proband carrying PER3rs772027021 SNP and SASH1 T525R mutation. Increased melanin synthesis was induced by PER3rs772027021 SNP in the melanocytes of affected epithelial tissues. Mutated SASH1 or PER3rs772027021 SNP alone or cooperation of mutation of SASH1 and PER3rs772027021 SNP synergistically led to increased melanin synthesis and enhanced proliferation of melanoma cells in vitro. We also phenotypically characterized a commercially available zebrafish mutant line harboring the PER3rs772027021 SNP to induce melanocyte proliferation in vivo. Our results are the first to reveal that this PER3 SNP may be pathogenic for a novel DUH subtype with mild hyperpigmented and/or hypopigmented phenotypes and that mutation of SASH1 and PER3 cooperatively promotes hyperpigmentation phenotypes. KEY MESSAGES: PER3 rs772027021 SNP is identified to be associated with hyperpigmentation and/or hypopigmentation phenotype and the novel pathogenic variant of PER3 rs772027021 SNP probably contributed the pathogenesis of DUH. SASH1T525R mutation is confirmed to associate with DUH. A novel autosomal dominant inheritance DUH subtype with mild pigmentated phenotypes is caused by the PER3rs772027021 SNP.

Mucosal Microbiota and Metabolome in the Ileum of Hu Sheep Offered a Low-Grain, Pelleted or Non-pelleted High-Grain Diet.

Alterations in mucosal microbiota and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC/MS) to investigate mucosal microbiota and their metabolic profiles in the ileum of Hu sheep fed different diets. Here, we randomly allocated 15 Hu sheep to three diets, a non-pelleted low-grain diet (control diet; CON), a non-pelleted high-grain diet (HG), and a pelleted high-grain diet (HP). After 60 days of treatment, ileal mucosal samples were collected for microbiome and metabolome analysis. The results of principal coordinate analysis and permutation multivariate analysis showed that there was a tendency for microbial differentiation between the CON and HG groups (P < 0.1), although no significant difference between the HG and HP groups was observed (P > 0.05). Compared with the CON diet, the HG diet decreased (P < 0.05) the abundance of some probiotic species (e.g., Sphingomonas and Candidatus Arthromitus) and increased (P < 0.05) the abundance of acid-producing microbiota (e.g., Succiniclasticum, Nesterenkonia, and Alloprevotella) in the ileal mucosa. Compared with the HG diet, the HP diet decreased (P < 0.05) the abundance of Alloprevotella and increased (P < 0.05) the abundance of Mycoplasma in the ileal mucosa. Furthermore, partial least squares discriminant analysis and orthogonal partial least-squared discriminant analysis indicated that different dietary treatments resulted in different metabolic patterns in the ileal mucosa of the CON, HG, and HP groups. The HG diet altered (VIP > 1 and P < 0.05) the metabolic patterns of amino acids, fatty acids, and nucleotides/nucleosides (such as increased amounts of ornithine, tyrosine, cis-9-palmitoleic acid, and adenosine) compared with the CON diet. However, 10 differential metabolites (VIP > 1 and P < 0.05; including tyrosine, ornithine, and cis-9-palmitoleic acid) identified in the HG group exhibited a diametrically opposite trend in the HP group, suggesting that the HP diet could partially eliminate the changes brought upon by the HG diet. Collectively, our findings demonstrate that different diets altered the ileal mucosal microbiota and metabolites and provide new insight into the effects of high-grain diets on the intestinal health of ruminant animals.

Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019.

To describe the epidemiological and clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) in Beijing. To analyze the application of corticosteroids in patients with severe pneumonia. We collected information on demographic characteristics, exposure history, clinical characteristics, corticosteroids use, and outcomes of the 65 confirmed cases of COVID-19 at Fifth Medical Center of PLA General Hospital from Jan 20 to Feb 23, 2020. The final follow-up date observed was April 15th, 2020. The number of patients with mild, general, severe, and critical type were 10 (15.38%), 32 (49.23%), 8 (12.31%), and 15 (23.08%), respectively. The median incubation period was 6 days. Notable outliers were 1 patient at 16 days and 1 patient at 21 days. In lymphocyte subgroup analysis, decreases in total, T, CD4, and CD8 lymphocytes were more common as the disease worsened (All P < 0.05). Methylprednisolone (mPSL) was applied to 31 (47.69%) patients with pneumonia, including 10 (31.25%) general, 8 (100%) severe, and 13 (86.67%) critical patients, respectively. Corticosteroids inhibited Interleukin-6(IL-6) production (P = 0.0215) but did not affect T lymphocyte (P = 0.0796). There was no significant difference between patients using lower dose (≤ 2 mg/kg day) and higher dose (> 2 mg/kg day) mPSL in inhibiting IL-6 production (P = 0.5856). Thirty of 31 patients (96.77%) had stopped mPSL due to improvement of pneumonia. Virus RNA clearance time lengthened with disease progression (P = 0.0001). In general type, there was no significant difference in virus clearance time between patients with (15, 12-19 days) and without (14.5, 11-18 days) (P = 0.7372) mPSL use. Lymphocyte, especially T lymphocyte, in severe and critical patients showed a dramatic decrease. Application of lower dose corticosteroids (≤ 2 mg/kg day) could inhibit IL-6 production (a representative of cytokines) as effectively as a higher dose. Proper use corticosteroids in general type patients did not delay virus clearance.

Ganoderma spore lipid protects mouse bone marrow mesenchymal stem cells and hematopoiesis from the cytotoxicity of the chemotherapeutic agent.

Cancer chemotherapeutic agents are frequently toxic to bone marrow and impair bone marrow functions. It is unclear whether ganoderma spore lipid (GSL) can protect bone marrow cells from the cytotoxicity of chemotherapy. To investigate the protective effects of GSL on bone marrow mesenchymal stem cells (MSCs) and hematopoiesis, we examined the effects of GSL on MSCs in vitro and hematopoiesis in vivo after treatment with the chemotherapeutic agent cyclophosphamide. MSCs and peripheral blood cells were isolated and counted from the bone marrow of normal mice were pre-treated with GSL before CTX treatment or co-treated with GSL and CTX, followed by examining the changes in phenotype, morphology, proliferation, apoptosis, and differentiation potentials. The results showed that GSL could reduce the CTX-induced changes in the phenotype of MSCs and maintain the elongated fibroblast-like morphology. MTT and annexin V/propidium iodide (PI) analyses found that GSL pre-treatment and co-treatment increased the proliferation and decreased the apoptosis in CTX-treated MSCs. Furthermore, GSL improved the osteogenic and adipogenic differentiation potentials of CTX-treated MSCs. In vivo, GSL treatment increased the number of peripheral blood cells including white blood cells (WBC) and platelets (PLT) in the CTX-treated mice and enhanced the in vitro formation of hematopoietic lineage colonies (erythrocyte colony forming unit, CFU-E; erythroid burst-forming units, BFU-E; and granulocyte macrophage colony-forming units, CFU-GM) from bone marrow cells in these mice. These findings suggest GSL could protect MSCs and hematopoiesis from the cytotoxicity of CTX and might become an effective adjuvant to attenuate side effects of chemotherapy during cancer treatment.

Analysis of Predictors of Type 2 Diabetes Mellitus Remission After Roux-en-Y Gastric Bypass in 101 Chinese Patients.

BACKGROUND: To investigate prognostic factors for complete remission in type 2 diabetes mellitus (T2DM) patients who underwent gastric bypass (GBP) and to establish a prognostic model for risk stratification. METHODS: We evaluated the baseline clinical features of patients with T2DM who received at Beijing Tian Tan Hospital from April 2012 to December 2015. Complete remission of T2DM was defined as meeting the following criteria: HbA1c < 6.5%, fasting plasma glucose (FPG) < 100 mg/dL, and absence of hypoglycemic drugs for 1 year following GBP. RESULTS: A total of 101 patients were enrolled in our study, and the complete remission rate of T2DM was 70.3% (71/101). Compared with patients with incomplete remission, patients with complete remission of T2DM had higher C-peptide levels, lower HbA1c, shorter disease duration, better ß cell function, and an absence of insulin therapy. HbA1c level, fasting C-peptide, duration of T2DM, and history of medical therapy were important prognostic factors for complete remission of T2DM (P = 0.001, 0.002, 0.01, 0.028, respectively). Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, fasting C-peptide higher than 1.2 ng/mL, and absence of insulin therapy before GBP achieved a higher complete remission rate of T2DM after GBP (AUC of the model was 0.825, 95% CI, 0.741-0.910; P = 0.001). CONCLUSIONS: The duration of T2DM, history of medical therapy, and levels of HbA1c and fasting C-peptide are independent predictors for the prognosis of T2DM patients undergoing GBP. Patients with HbA1c lower than 7.5%, a history of T2DM shorter than 9.5 years, a fasting C-peptide higher than 1.2 ng/mL, and an absence of insulin therapy may have a higher complete remission rate of T2DM after GBP.

lncRNA PVT1 promotes the angiogenesis of vascular endothelial cell by targeting miR­26b to activate CTGF/ANGPT2.

Angiogenesis is essential for various biological processes, including tumor blood supply delivery, cancer cell growth, invasion and metastasis. Plasmacytoma variant translocation 1 (PVT1) long noncoding RNA (lncRNA) has been previously reported to affect angiogenesis of glioma microvascular endothelial cells by regulating microRNA (miR)­186 expression level. However, the specific underlying molecular mechanism of PVT1 regulation of angiogenesis in vascular endothelial cells remains to be elucidated. The present study investigated the role of PVT1 in cell proliferation, migration and vascular tube formation of human umbilical vein endothelial cells (HUVECs) using MTT assay, Transwell migration assay and in vitro vascular tube formation assay, respectively. In order to determine the effect of miR­26b on cell proliferation, migration and vascular tube formation of HUVECs, miR­26 mimic or miR­26b inhibitor were transfected into HUVECs. Reverse transcription­quantitative polymerase chain reaction and western blotting were conducted to quantify the mRNA and protein expression levels of target genes. The present study confirmed that miR­26b bound 3'­untranslated region (3'­UTR) and subsequently influenced gene expression level using dual luciferase reporter assay. The current study observed that PVT1 affected cell proliferation, migration and in vitro vascular tube formation of HUVECs. In addition, it was determined that PVT1 was able to bind and degrade miR­26b to promote connective tissue growth factor (CTGF) and angiopoietin 2 (ANGPT2) expression. miR­26b was also identified to have a suppressive role in cell proliferation, migration and in vitro vascular tube formation of HUVECs via binding 3'­UTR regions and downregulating CTGF and ANGPT2 expression levels. The current findings may improve the understanding of the underlying mechanism of PVT1 contributing to angiogenesis of vascular endothelial cells and offer rationale for targeting PVT1 to treat angiogenesis dysfunction­associated diseases, including cancer metastasis.

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.

Acute Lymphoblastic Leukemia in the Course of Polycythemia Vera: A Case Report and Review of Literature.

INTRODUCTION: Polycythemia vera (PV) is one of the most common forms of myeloproliferative neoplasms. Acute myeloid leukemia secondary to PV is well reported, and the mechanism has been clarified to some extent. Only a limited number of cases have been reported about the development of acute lymphoblastic leukemia (ALL) in the course of PV, and the possible underlying mechanism has not been explored well. CASE PRESENTATION: A 75-year-old patient who developed ALL 3 years after he was diagnosed with PV. The presence of remarkable splenomegaly, typical immunophenotyping of the peripheral blood and increased expression of serum fibrosis markers indicated the existence of extramedullary hematopoiesis which may ascribe to myelofibrosis. After the treatment of dosage-modulated chemotherapy, the patient got complete remission. CONCLUSION: The JAK2 mutation may the underlying factor that contributes to the development of ALL, and the existence of MF may indicate the progression to post- polycythemic MF, which may be a risk factor for the accelerated transformation.

PTP4A3 is a target for inhibition of cell proliferatin, migration and invasion through Akt/mTOR signaling pathway in glioblastoma under the regulation of miR-137.

Glioblastoma multiforme (GBM) is one of the most common primary malignant adult brain tumors. It is characterized by aggressive progression and poor prognosis. There is significant need to understand the mechanism of GBM malignancy and develop improved therapeutic options for GBM patients. We systematically studied the function of PTP4A3 in the malignancy of GBM. We found that PTP4A3 was upregulated in GBM tissues and cells. Knockdown of PTP4A3 expression in GBM cells inhibited cell proliferation, migration, and invasion. PTP4A3 knockdown modulated the activity of the Akt/mTOR signaling pathway by inducing de-phosphorylation of Akt and mTOR. We identified PTP4A3 as a direct target of miR-137. MiR-137 has been reported as a tumor suppressor in GBM development. In this study, overexpression of miR-137 in GBM cells also inhibited cell proliferation, migration, and invasion. Finally, restoration of PTP4A3 expression in miR-137 overexpressing cells partially reversed the inhibition of GBM cell malignancy, and the de-phosphorylation of Akt and mTOR. We identified that PTP4A3 regulated GBM via miR-137-mediated Akt/mTOR signaling pathway.

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.

Antithrombotic effect of grape seed proanthocyanidins extract in a rat model of deep vein thrombosis.

OBJECTIVE: Proanthocyanidins are abundantly found in grape seeds and have been suggested to inhibit the pathogenesis of systemic diseases. We investigated the antithrombotic effects of proanthocyanidins in a rat model of deep vein thrombosis (DVT) and examined the underlying mechanisms. METHODS: DVT was induced in rat model by inferior vena cava (IVC) ligation. Grape seed proanthocyanidins extract (GSPE, 400 mg/kg/d) dissolved in saline (2 mL) was orally administered to the experimental rats. Control rats were administrated saline (2 mL) only. The thrombi were harvested and weighed. The IVC was analyzed histologically and by transmission electron microscopy. The cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay. Expression of cellular adhesion molecules (CAMs) in thrombi was examined by Western blot. RESULTS: GSPE significantly reduced thrombus length and weight (P < .01) and protected the integrity of the endothelium. GSPE inhibited thrombogenesis-promoting factors P-selectin, von Willebrand factor, and CAMs, and promoted thrombogenesis-demoting factors CD34, vascular endothelial growth factor receptor-2, and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type one motif, member 13). Compared with the control, GSPE significantly lowered the cytokines IL-6 (74.19 ± 13.86 vs 189.54 ± 43.76 pg/mL; P < .01), IL-8 (80.71 ± 21.42 vs 164.56 ± 39.54 pg/mL; P < .01), and TNF-α (43.11 ± 17.58 vs 231.84 ± 84.11 pg/mL; P < .01). CONCLUSIONS: GSPE significantly inhibited the propagation of thrombus induced by IVC ligation in a rat model. The antithrombotic properties of proanthocyanidins are likely to be directly associated with endothelial protection and regeneration, platelet aggregation, and inhibition of inflammatory cell and thrombus adhesion. Thus, proanthocyanidins may have a clinical application in DVT treatment.