[Chemical constituents and anti-liver fibrosis mechanism of Meconopsis quintuplinervia based on UPLC-Q-Exactive-MS/MS and network pharmacology].

In this study, UPLC-Q-Exactive-MS/MS was used to rapidly analyze the chemical constituents of Meconopsis quintupli-nervia, and the anti-liver fibrosis mechanism of M. quintuplinervia was preliminarily analyzed by network pharmacology, molecular docking, and cell experiments. The chemical constituents of M. quintuplinervia were identified according to the information of MS~1 and MS~2, as well as the data in the literature and databases. SwissTargetPrediction and TargetNet were used to predict the potential targets. The targets related to liver fibrosis were collected from GeneCards and OMIM. The protein-protein interaction(PPI) network was constructed by STRING. Cytoscape 3.6.1 was used to construct and analyze the "constituent-target-disease" network to obtain key targets and their corresponding constituents in the network. DAVID 6.8 was used for GO analysis and KEGG signaling pathway enrichment analysis. Finally, the preliminary verification was carried out by molecular docking and cell experiments. As a result, 106 chemical constituents were identified from M. quintuplinervia, including 66 flavonoids, 16 alkaloids, 18 phenolic acids, 1 anthocyanin, and 5 other constituents. Among them, 3 constituents were identified as potential new compounds, and 59 constituents were reported in M. quintuplinervia for the first time. Network pharmacology analysis showed that M. quintuplinervia presumably acted on AKT1, SRC, JUN, EGFR, STAT3, HSP90 AA1, MAPK3, and other core targets through luteolin, isorhamnetin, quercetin, apigenin, kaempferide, amurine, 2-methylflavinantine, allocryptopine, the multi and other active compounds, thereby regulating the PI3 K/AKT signaling pathway, pathways in cancer, proteoglycans in cancer, FoxO signaling pathway, and other pathways to exert anti-liver fibrosis effects. M. quintuplinervia extract(MQE) could significantly down-regulate PI3 K and AKT protein levels in the HSC-T6 cell model induced by TGF-ß1, suggesting that MQE may have the ability to regulate the PI3 K/AKT signaling pathway. The findings of this study indicated that the anti-liver fibrosis effect of M. quintuplinervia had multi-constituent, multi-target, and multi-pathway characteristics, which may provide a scientific basis for the research on the pharmacodynamic materials, action mechanism, and quality markers of M. quintupli-nervia.

Dinuclear Nickel Complexes Using Hexadentate Benzothiazole-Based Diamine-Bisphenolate Ligands: Highly Active Catalysts for Copolymerization of Carbon Dioxide with Epoxides.

We reported for the first time the utilization of hexadentate benzothiazole-based diamine-bisphenolate ligands to synthesize structurally well-characterized dinickel dicarboxylate complexes and studied their catalysis for copolymerization of carbon dioxide with epoxides. Dinickel carboxylate complexes having a 1,3-diamine-bridged backbone were demonstrated to be high-performance catalysts for alternating copolymerization of CO2 and cyclohexene oxide (CHO) with high product selectivity. Particularly, acetate-supported nickel complex 2 enabled us to promote such CO2-copolymerization of this kind with a maximum turnover frequency of up to 2600 h-1 and gave good molecular weight controllability under high-pressure conditions. It is worth noting that bimetallic Ni catalyst 2 was also capable of mediating the catalytic CO2-polymerization of alicyclic epoxides at atmospheric pressure. Kinetic investigations of CO2/CHO copolymerization by 2 allowed us to determine the rate equation of -d[CHO]/dt = kp[2]1[CHO]1, and such catalysis exhibited a first-order dependence on both dinickel complex and CHO concentrations.

Simultaneous enhancement of nitrate removal flux and methane utilization efficiency in MBfR for aerobic methane oxidation coupled to denitrification by using an innovative scalable double-layer membrane.

Endevours on the enhancement of nitrate removal efficiency during methane oxidation coupled with denitrification (AME-D) has always overlooked the role of membrane employed. It would be highly beneficial to enrich the biomass content and to manage biofilm on the membrane, in the utilization of methane and denitrification. In this study, an innovative and scalable double-layer membrane (DLM) was designed and prepared for a membrane biofilm reactor (MBfR), to simultaneously enhance nitrate removal flux and methane utilization efficiency during aerobic methane oxidation coupled with the denitrification (AME-D) process. The DLM allowed quick bacterial attachment and biomass accumulation for biofilm growth, which would be then self-regulated for well distribution of functional microbes on/within the DLM. Upon a high biofilm density of over 70 g-VSS m-2 achieved on the DLM, the methane utilization efficiency of the MBfR was enhanced significantly to over 1.3 times than the control MBfR with conventional polypropylene membrane. The MBfR employed DLM also demonstrated the maximum nitrate removal flux of 740 mg-NO3--N m-2 d-1 that was approximately 1.64 times of that in control MBfR at continuous-mode operation. This DLM indeed favored the enrichment of Type II aerobic methanotrophs of Methylocystaceae, and methanol-utilization denitrifiers of Rhodocyclaceae that preferentially utilize methanol as the cross-feeding intermediates to promote the methane utilization efficiency, and thus to enhance the nitrate removal flux. These results raised from new designed DLM confirmed the importance of membrane surface properties on the effectiveness of MBfR, and offered great potential to address challenging problems of MBfRs during engineering application.

Assessment of the radiation effect of aerosols on maize production in China.

With the recent increases in atmosphere aerosol concentration, its impact on agriculture in China is of considerable concern for scientific community. In this study, the effects that aerosols have on radiation and consequently the production of maize in China were investigated from 2002 to 2014 using the AErosol RObotic NETwork (AERONET) data, Second Simulation of a Satellite Signal in the Solar Spectrum radiative transfer (6S) model, and Agricultural Production Systems sIMulator (APSIM) model. Ten stations in the maize planting areas including Beijing, Xianghe, Taihu, Nanjing, Shanghai, Hefei, Baotou, Lanzhou, Qinghaihu, and Xuzhou stations were selected. The results showed that the APSIM-maize model, which was further calibrated, was able to simulate the interactions between maize and the climatic constraints in the maize planting areas of China. Our results indicated that aerosols obviously reduced the amount of solar radiation reaching the surface during the maize growing season in China. We also found that the aerosols have negative effects on both biomass and yield of maize in China at ten stations. The average annual maize biomass during the maize growing season from 2002 to 2014 decreased by 23.70%. The average yield of maize from 2002 to 2014 decreased by 15.10%. However, the influence of aerosol on different varieties of maize varied. We found the aerosols had greater negative impacts on summer maize than on spring maize. For spring maize, the average biomass and yield from 2002 to 2014 decreased by 10.36% and 5.16%, respectively. However, as for the summer maize, the average biomass and yield from 2002 to 2014 were reduced by 19.72% and 20.56%, respectively. Our findings can provide a useful method for estimating the effect of aerosols on crops at the national level, supporting local agricultural production in coping with the ongoing climate change.

[Significance of Neutrophil/Lymphocyte Ratio and Platelet/Lymphocyte Ratio in Patients with Multiple Myeloma].

OBJECTIVE: To investigate the significance of neutrophil/lymphocyte ratio(NLR) and platelet/lymphocyte ratio(PLR) in patients with multiple myeloma (MM). METHODS: Eighty patients with multiple myeloma admitted in our hospital from August 2007 to August 2010 were selected. The clinical data of the patients, including hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), white blood cell(WBC) count, absolute neutrophil count (ANC), platelet count (PC), glomerular filtration rate (GFR), calcium, albumin, ß2 microglobulin and so on were collected and analyzed. RESULTS: The optimal threshold of NLR was 2.78 (sensitivity: 83.3%, specificity: 43.1%). The optimal threshold of PLR was 155.58 (sensitivity: 67.7%, specificity: 36.9%). All patients were grouped according to NLR and PLR values, patients with high NLR and PLR had lower albumin levels and higher clinical stages. High NLR patients were mainly men, hemoglobin, GFR values, albumin levels were lower, and the white blood cells count and ß2 microglobulin level were higher. High PLR patients showed low albumin level and higher clinical stage. Multivariate analysis showed that ß2 microglobulin and NLR were prognostic factors in patients with multiple myeloma (P<0.05). Kaplan-Meier survival analysis showed that the median survival time was 37 months (95% CI: 21.80-52.19) for patients with high NLR and 66 months (95% CI: 53.19-78.80) for patients with low NLR. The median survival time was 45 months (95% CI: 0.00 to 91.18) in patients with high PLR and 62 months (95% CI: 45.67-78.33) in patients with low PLR. CONCLUSION: High NLR (>2.78) associates with poor prognosis in patients with MM, and it may be considered as an independent prognostic factor for MM patients.

[Expression and Significance of PTEN and BCL-2 in Acute Myeloid Leukemia].

OBJECTIVE: To explore the expression of phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B-cell lymphoma/leukemia-2 (BCL-2) in acute myeloid leukemia (AML) and its significance. METHODS: The expression levels of PTEN and BCL-2 mRNA and protein in bone marrow samples from 80 AML patients including 56 de novo patients, 16 patients in remission, 8 relapsed patients and 30 cases of non-hematologic diseases (as control) were detected by real-time PCR and Western blot, respectively, and the relationship between PTEN and BCL-2 expression and clinical pathological parameter was analyzed. RESULTS: The expression levels of both mRNA and protein of PTEN in newly diagnosed AML group and relapse group were significantly lower than those in the control and remission group (P<0.01). The expression levels of both mRNA and protein of BCL-2 in newly diagnosed group and relapse group were significantly higher than those in the control and remission group (P<0.01). The mRNA expression of PTEN and BCL-2 was did not related with the age, sex and white blood count in AML patients. The expression levels of PTEN negatively correlated with expression BCL-2 with AML(r=-0.432, r=-0.569). CONCLUSION: PTEN and BCL-2 participate in the occurrence and development of AML, and may be used as indicators for the evaluation of chemotheraeutic efficacy.

[Transurethral diode laser enucleation versus transurethral electrovaporization resection of the prostate for benign prostatic hyperplasia with different prostate volumes].

OBJECTIVE: To compare the clinical effect of diode laser enucleation of the prostate (DIOD) with that of transurethral resection of the prostate (TURP) on benign prostate hyperplasia (BPH) with different prostate volumes. METHODS: This retrospective study included 256 BPH patients treated by DIOD (n = 141) or TURP (n = 115) from March 2012 to August 2015. According to the prostate volume, we divided the patients into three groups: <60 ml (42 for DIOD and 31 for TURP), 60－80 ml (51 for DIOD and 45 for TURP), and >80 ml (48 for DIOD and 39 for TURP). We obtained the relevant data from the patients before, during and at 6 months after surgery, and compared the two surgical strategies in operation time, perioperative levels of hemoglobin and sodium ion, post-operative urethral catheterization time and bladder irrigation time, pre- and post-operative serum PSA levels, International Prostate Symptoms Score (IPSS), post-void residual urine (PVR) volume and maximum urinary flow rate (Qmax), and incidence of post-operative complications among different groups. RESULTS: In the <60 ml group, there were no remarkable differences in the peri- and post-operative parameters between the two surgical strategies. In the 60－80 ml group, DIOD exhibited a significant superiority over TURP in the perioperative levels of hemoglobin (ï¼»3.25 ± 1.53ï¼½ g/L vs ï¼»4.77 ± 1.67ï¼½ g/L, P <0.05) and Na+ (ï¼»3.58 ± 1.27ï¼½mmol/L vs ï¼»9.67 ± 2.67ï¼½ mmol/L, P <0.01), bladder irrigation time (ï¼»30.06 ± 6.22ï¼½h vs ï¼»58.32 ± 10.25ï¼½ h, P <0.01), and urethral catheterization time (ï¼»47.61 ± 13.55ï¼½ h vs ï¼»68.01 ± 9.69ï¼½ h, P <0.01), but a more significant decline than the latter in the postoperative PSA level (ï¼»2.34 ± 1.29ï¼½ ng/ml vs ï¼»1.09 ± 0.72ï¼½ ng/ml, P <0.05), and similar decline was also seen in the >80 ml group (ï¼»3.35 ± 1.39ï¼½ ng/ml vs ï¼»1.76 ± 0.91ï¼½ ng/ml, P <0.05). No blood transfusion was necessitated and nor postoperative transurethral resection syndrome or urethral stricture observed in DIOD. However, the incidence rate of postoperative pseudo-urinary incontinence was significantly higher in the DIOD (22.7%, 32/141) than in the TURP group (7.83%, 9/115) (P <0.05). CONCLUSIONS: DIOD, with its obvious advantages of less blood loss, higher safety, faster recovery, and more definite short-term effectiveness, is better than TURP in the treatment of BPH with medium or large prostate volume and similar to the latter with small prostate volume.

Treatment and Prognosis of Anaplastic Thyroid Carcinoma: A Clinical Study of 50 Cases.

INTRODUCTION: Although anaplastic thyroid carcinoma (ATC) is rare, it is one of the most aggressive human cancers. The optimal multimodal therapy policy of ATC is still debated, and a standardized treatment strategy remains to be established. This study aimed to evaluate the management aspect and prognosis of ATC. MATERIALS AND METHODS: The data were analyzed retrospectively for 50 patients with ATC to evaluate the clinical characters, management and factors influencing survival. Survival analysis was performed by Kaplan-Merier method and log-rank test, and multivariate analysis was performed using Cox proportional hazard model. RESULTS: The 1-year and 2-year overall survival rates (OS) were 48.0% and 26.0% respectively in all patients, with the 2-year OS of 40.0% and 31.0% and 6.3% for stage IVA, IVB and IVC respectively (P <0.05). In stage IVA and IVB patients, combined surgery with radiotherapy improved overall survival, and the 2-year OS were 50.0% and 35.7% respectively in the group with combined surgery with radiotherapy and the group with surgery with only (P <0.05). Postoperative radiotherapy improved local control rate in stage IVA and IVB patients (P <0.05). However, surgery, radiotherapy or chemotherapy could not improve the survival of stage IVC patients. Multivariate analysis showed that distant metastases, surgery, radiotherapy and tumor residue could predict the prognosis. CONCLUSION: Combined surgery and radiotherapy could improve overall survival in stage IVA and IVB patients. Patients with ATC have a bad prognosis. Distant metastases, surgery, radiotherapy and tumor residue are the most important factors affecting the prognosis.

Correction: Xiang, S., et al. Schisandrin B Induces Apoptosis and Cell Cycle Arrest of Gallbladder Cancer Cells. Molecules 2014, 19, 13235-13250.

We would like to change the Affiliation addresses on Page 13235 of paper [1], [...].

Baicalein inhibits progression of gallbladder cancer cells by downregulating ZFX.

Baicalein, a widely used Chinese herbal medicine, has multiple pharmacological activities. However, the precise mechanisms of the anti-proliferation and anti-metastatic effects of baicalein on gallbladder cancer (GBC) remain poorly understood. Therefore, the aim of this study was to assess the anti-proliferation and anti-metastatic effects of baicalein and the related mechanism(s) on GBC. In the present study, we found that treatment with baicalein induced a significant inhibitory effect on proliferation and promoted apoptosis in GBC-SD and SGC996 cells, two widely used gallbladder cancer cell lines. Additionally, treatment with baicalein inhibited the metastasis of GBC cells. Moreover, we demonstrated for the first time that baicalein inhibited GBC cell growth and metastasis via down-regulation of the expression level of Zinc finger protein X-linked (ZFX). In conclusion, our studies suggest that baicalein may be a potential phytochemical flavonoid for therapeutics of GBC and ZFX may serve as a molecular marker or predictive target for GBC.

The utility of fluorescence in situ hybridization for diagnosis and surveillance of bladder urothelial carcinoma.

PURPOSE: To evaluate the clinical value of fluorescence in situ hybridization (FISH) for diagnosis and surveillance of bladder urothelial carcinoma (BUC). MATERIALS AND METHODS: Between November 2010 and December 2013, patients suspected of having BUC were examined using urine cytology and FISH assay. Based on histopathological examination results, FISH results were com­pared with urine cytology. In addition, patients with a history of non-muscle invasive BUC were also examined using urine cytology and FISH assay at the first time of visit and then monitored with cystoscopy during follow-up period. RESULTS: A total of 162 patients included in this study and 12 patients were excluded due to uninformative FISH assays. The remaining 150 patients consisted of 108 patients suspected for BUC and 42 patients with a history of non-muscle invasive BUC. The sensitivities of FISH analysis and urine cytology were 72.8% and 27.2%, respectively, and the difference was statistically significant (P <.05). Difference between specificity of urine cytology (100%) and FISH assay (85%) was not statistically significant (P >.05). At the first visit, of 42 patients, one patient had positive cystoscopy, and FISH assay was positive in 26 of 41 patients with negative cystoscopy. During the follow-up period (mean, 29.5 months), 18 of 26 patients developed recurrence, and recurrence occurred in only one of 15 patients with negative FISH analysis. CONCLUSION: Our results suggest that FISH analysis can be used as a non-invasive diagnostic tool for patients suspect­ed of having new BUC. In addition, FISH analysis may provide important prognostic information to better define the individual risk for BUC recurrence.& nbsp;

Bufalin induces cell cycle arrest and apoptosis in gallbladder carcinoma cells.

Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine Chan Su, has been shown to exert a potential for anticancer activity against various human cancer cell lines in vitro. However, no detailed studies have so far been reported on its action on human gallbladder carcinoma cells. In this study, bufalin remarkably inhibited growth in human gallbladder cancer cells by decreasing cell proliferation, inducing cell cycle arrest and apoptosis in a dose-dependent manner. Bufalin also disrupted the mitochondrial membrane potential (ΔΨm) and regulated the expression of cell cycle and apoptosis regulatory molecules. Activation of caspase-9 and the subsequent activation of caspase-3 indicated that bufalin may be inducing mitochondria apoptosis pathways. Intraperitoneal injection of bufalin for 3 weeks significantly inhibited the growth of gallbladder carcinoma (GBC-SD) xenografts in athymic nude mice. Taken together, the results indicate that bufalin may be a potential agent for the treatment of gallbladder cancer.

Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study.

BACKGROUND: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection. METHODS: We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration. RESULTS: The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen. CONCLUSIONS: Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.

Cordycepin induces S phase arrest and apoptosis in human gallbladder cancer cells.

Gallbladder cancer is the most common malignant tumor of the biliary tract, and this condition has a rather dismal prognosis, with an extremely low five-year survival rate. To improve the outcome of unresectable and recurrent gallbladder cancer, it is necessary to develop new effective treatments and drugs. The purpose of the present study was to evaluate the effects of cordycepin on human gallbladder cells and uncover the molecular mechanisms responsible for these effects. The Cell Counting Kit-8 (CCK-8) and colony formation assays revealed that cordycepin affected the viability and proliferation of human gallbladder cancer cells in a dose- and time-dependent manner. Flow cytometric analysis showed that cordycepin induced S phase arrest in human gallbladder cancer cell lines(NOZ and GBC-SD cells). Cordycepin-induced apoptosis was observed using an Annexin V/propidium iodide (PI) double-staining assay, and the mitochondrial membrane potential (ΔΨm) decreased in a dose-dependent manner. Additionally, western blot analysis revealed the upregulation of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP and Bax and the downregulation of Bcl-2, cyclin A and Cdk-2 in cordycepin-treated cells. Moreover, cordycepin inhibited tumor growth in nude mice bearing NOZ tumors. Our results indicate that this drug may represent an effective treatment for gallbladder carcinoma.

Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells.

Gallbladder cancer, with high aggressivity and extremely poor prognosis, is the most common malignancy of the bile duct. The main objective of the paper was to investigate the effects of schisandrin B (Sch B) on gallbladder cancer cells and identify the mechanisms underlying its potential anticancer effects. We showed that Sch B inhibited the viability and proliferation of human gallbladder cancer cells in a dose-, time -dependent manner through MTT and colony formation assays, and decrease mitochondrial membrane potential (ΔΨm) at a dose-dependent manner through flow cytometry. Flow cytometry assays also revealed G0/G1 phase arrest and apoptosis in GBC-SD and NOZ cells. Western blot analysis of Sch B-treated cells revealed the upregulation of Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP and downregulation of Bcl-2, NF-κB, cyclin D1 and CDK-4. Moreover, this drug also inhibited the tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data demonstrated that Sch B induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that Sch B may be a promising drug for the treatment of gallbladder cancer.

[Shang Ring circumcision by transverse incision in the distal penis foreskin and pull-up of the interior board for short frenulum praeputii].

OBJECTIVE: To investigate the effectiveness of surgical strategies for Shang Ring circumcision in the treatment of short frenulum praeputii in patients with redundant prepuce or phimosis. METHODS: Totally, 130 cases of short frenulum praeputii with redundant prepuce or phimosis were randomly assigned to an experimental group and a control group of equal number to receive Shang Ring circumcision, the former by transverse incision in the distal penis foreskin and pull-up of the interior board, and the latter by conventional transverse incision and longitudinal suture of the frenulum praeputii. Comparisons were made between the two groups in the surgical duration, intraoperative blood loss, 24 h postoperative pain visual analog score (VAS), postoperative complications, satisfaction with the penile appearance, and the quality of sexual life. RESULTS: The surgical duration, intraoperative blood loss, 24 h postoperative VAS, postoperative sexual satisfaction, and satisfaction with penile appearance were (4.60 +/- 1.20) min, (2.61 +/- 1.81) ml, 1.73 +/- 0.76, 98.5%, and 98.5%, respectively, in the experimental group, as compared with (21.60 +/- 6.30) min, (11.10 +/- 3.40) ml, 5.37 +/- 1.84, 70.3% and 69.8% in the control, with statistically significant differences between the two groups (P < 0.05). The incidence rates of such major complications as wound dehiscence, infection, and moderate to severe edema were 1.5% (1/65), 3.1% (2/65), and 4.6% (3/65), respectively, in the experimental group in comparison with 12.3% (8/65), 15.3% (10/65), and 30.7% (20/65) in the control, with statistically significant differences between the two groups (P < 0.05). None of patients had any serious complications. CONCLUSION: Shang Ring circumcision by transverse incision in the distal penis foreskin and pull-up of the interior board, with its advantages of shorter operation time, less blood loss, mild pain, fewer complications, and higher satisfaction and acceptance of the patients, can be used as an safe and effective approach to the treatment of short frenulum praeputii.

Effects of oxymatrine on the apoptosis and proliferation of gallbladder cancer cells.

Gallbladder carcinoma is the most common malignancy of the biliary tract and is associated with a very poor outcome. The aim of the present study was to investigate the effects of oxymatrine (OM) on gallbladder cancer cells and the possible mechanism of its effects. The effects of OM on the proliferation of gallbladder cancer cells (GBC-SD and SGC-996) were investigated using cell counting kit-8 and colony formation assays. Annexin V/propidium iodide double staining was performed to investigate whether OM could induce apoptosis in gallbladder cancer cells. The mitochondrial membrane potential (ΔΨm) and expression of apoptosis-associated proteins were evaluated to identify a mechanism for the effects of OM. In addition, the RNA expression of relevant genes was measured by qRT-PCR using the SYBR Green method. Finally, a subcutaneous implantation model was used to verify the effects of OM on tumor growth in vivo. We found that OM inhibited the proliferation of gallbladder cancer cells. In addition, Annexin V/propidium iodide double staining showed that OM induced apoptosis after 48 h and the ΔΨm decreased in a dose-dependent manner after OM treatment. Moreover, the activation of caspase-3 and Bax and downregulation of Bcl-2 and nuclear factor κB were observed in OM-treated cells. Finally, OM potently inhibited in-vivo tumor growth following subcutaneous inoculation of SGC-996 cells in nude mice. In conclusion, OM treatment reduced proliferation and induced apoptosis in gallbladder cancer cells, which suggests that this drug may serve as a novel candidate for adjuvant treatment in patients with gallbladder cancer.

MALAT1 promotes the proliferation and metastasis of gallbladder cancer cells by activating the ERK/MAPK pathway.

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway.

Baicalin induces apoptosis of gallbladder carcinoma cells in vitro via a mitochondrial-mediated pathway and suppresses tumor growth in vivo.

Baicalin, the main active ingredient in the Scutellaria baicalensis (SB), is prescribed for the treatment of various inflammatory diseases and tumors in clinics in China. In the present study, we evaluated the antitumor activity of baicalin for gallbladder carcinoma and the underlying mechanisms both in vitro and in vivo. Our results indicate that baicalin induced potent growth inhibition, cell cycle arrest, apoptosis and colony-formation inhibition in a dose-dependent manner in vitro. We observed inhibition of NF-κB nuclear translocation, up-regulation of Bax and down-regulation of Bcl-2, as well as increased caspase-3 and caspase-9 expression after baicalin treatment in vitro and in vivo, which indicates that the mitochondrial pathway was involved in baicalin-induced apoptosis. In addition, daily intraperitoneally injection of baicalin (15, 30 and 60 mg/kg) for 21 days significantly inhibited the growth of NOZ cells xenografts in nude mice, which improved the survival of baicalin-treated mice. In summary, baicalin exhibited a significant anti-tumor effect by suppressing cell proliferation, promoting apoptosis, and inducing cell cycle arrest in vitro, and by suppressing tumor growth and improving survival in vivo, which suggested that baicalin represents a novel therapeutic option for gallbladder carcinoma.

Evaluation of two inflammation-based prognostic scores in patients with resectable gallbladder carcinoma.

BACKGROUND: Survival after surgery for gallbladder cancer is generally poor. A number of inflammation-based prognostic scores have been established to help predict survival after surgery for several types of cancer. The objective of this study was to analyze and compare the utility of two inflammation-based prognostic scores, the Glasgow prognostic score (GPS) and the neutrophil-to-lymphocyte ratio (NLR), for predicting survival in patients with gallbladder cancer after surgery with curative intent. METHODS: We retrospectively reviewed the medical records of 85 patients with histologically confirmed, resectable gallbladder carcinoma (GBC), who were to receive curative surgery in our department. Univariate and multivariate analyses were performed to evaluate the relationship between the variables to overall survival (OS). RESULTS: A significant difference was detected in OS in patients with low and high GPS and NLR scores. Univariate analyses using clinicopathological characteristics revealed that tumor differentiation; tumor invasion; lymph node metastasis; tumor, node, metastasis classification system stage; positive margin status; combined common bile duct resection; serum levels of C-reactive protein, albumin, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and CA125; white blood cell count; and GPS and NLR were all associated with OS. Among these characteristics, multivariate analysis demonstrated that a high GPS was independently associated with poorer OS, together with tumor invasion, lymph node metastasis, and positive margin status. CONCLUSIONS: GPS is superior to NLR with respect to its prognostic value for patients with GBC after surgery with curative intent. GPS is not only associated with tumor progression but is also an independent marker of poor prognosis.