Scutellaria barbate extract induces apoptosis of hepatoma H22 cells via the mitochondrial pathway involving caspase-3

AIM： To study the growth inhibitory and apoptotic effects of Scutellaria barbata D.Don （S. barbata） and to determine the underlying mechanism of its antiturnor activity in mouse liver cancer cell line H22.METHODS： Proliferation of H22 cells was examined by MTT assay. Cellular morphology of PC-2 cells was observed under fluorescence microscope and transmission electron microscope （EM）. Mitochondrial transmembrane potential was determined under laser scanning confocal microscope （LSCM） with rhodamine 123 staining. Flow cytometry was performed to analyze the cell cycle of H22 cells with propidium iodide staining. Protein level of cytochrome C and caspase-3 was measured by semi-quantitive RT-PCR and Western blot analysis. Activity of caspase-3 enzyme was measured by spectrofluorometrv.RESULTS： M-I-I- assay showed that extracts from S. barbata （ESB） could inhibit the proliferation of H22 cells in a time-dependent manner. Among the various phasesof cell cycle, the percentage of cells in S phase was significantly decreased, while the percentage of cells in G1 phase was increased. Flow cytometry assay also showed that ESB had a positive effect on apoptosis. Typical apoptotic morphologies such as condensation and fragmentation of nuclei and blebbing membrane of apoptotic cells could be observed under transmission electron microscope and fluorescence microscope. To further investige the molecular mechanism behind ESB-induced apoptosis, ESB-treated cells rapidly lost their mitochondrial transmembrane potential, released mitochondrial cytochrome C into cytosol, and induced caspase-3 activity in a dose-dependent manner. CONCLUSION： ESB can effectively inhibit the proliferation and induce apoptosis of H22 cells involving loss of mitochondrial transmembrane potential, release of cytochrome C, and activation of caspase-3.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography- electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 ± 90, 122 ± 54, 61 ± 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 ± 84, 188 ± 91, and 93 ± 45 ng/ mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 ± 9.4 and 35.8 ± 5.5/highpower field (hpf), respectively, which were significantly more than that in the normal group (29.8 ± 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 ± 9.4, 35.8 ± 5.5, 29.8 ± 4.4/hpf, respectively) than at the duodenum (19.6 ± 4.7, 18.5 ± 6.3, 19.2 ± 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

Efficacy and safety of gemcitabine-oxaliplatin combined with huachansu in patients with advanced gallbladder carcinoma

AIM: To evaluate the efficacy and safety of gemcitabine-oxaliplatin (GEMOX) combined with huachansu (cinobufagin) injection treatment in patients with locally advanced or metastatic gallbladder carcinoma (GBC), and to assess the quality of life (QOL) of such patients. METHODS: Twenty-fi ve patients with locally advanced or metastatic GBC were treated with intravenous gemcitabine (1000 mg/m2) over 30 min on days 1 and 8, 2 h infusion of oxaliplatin (120 mg/m2) on day 1, and 2-3 h infusion of huachansu (20 mL/m2) on days -3-11, every 3-4 wk. Treatment was continued until occurrence of unacceptable toxicity or disease progression. QOL of patients was assessed by the EORTC QLQ-C30 at baseline, at the end of the fi rst, third and sixth chemotherapy cycles, and 1 mo after the treatment. RESULTS: Among the 25 patients with a median age of 64 years (range 42-78 years), 23 were evaluable in the study. A total of 137 cycles of therapy were performed and the median cycle was 5 (range 1-8) per patient. Out of the 23 patients whose response couldbe evaluated, 8 partial responses (PR) were observed (34.8%), while 7 patients (30.4%) demonstrated a stable disease (SD). The disease control rate was 65.2%. Progression of cancer was observed in 8 (34.8%) patients. The median progression-free and overall survival time was 5.8 mo (95% CI: 4.5-7.1 mo) and 10.5 mo, respectively. The therapy was well tolerated, with moderate myelosuppression as the main toxicity. Anemia grade 2 was seen in 16.0%, neutropenia grade 3 in 8.0% and thrombocytopenia grade 3 in 24.0% of patients, respectively. Non-hematologic toxicity ranged from mild to moderate. No death occurred due to toxicity. The QOL of patients was improved after chemotherapy, and the scores of QOL were increased by 10 to 20 points. CONCLUSION: GEMOX combined with huachansu (cinobufagin) injection is well tolerated, effective, thus improving the QOL of patients with advanced GBC.

Fast magnetic reconstruction of the portal vein with allogeneic blood vessels in canines

BACKGROUND： The resection and reconstruction of large vessels, including the portal vein, are frequently needed in tumor resection. Warm ischemia before reconstruction might have deleterious effects on the function of some vital organs and therefore, how to reconstruct the vessels quickly after resection is extremely important. The present study was to introduce a new type of magnetic compression anastomosis （MCA） device to establish a quick non-suture anastomosis of the portal vein after resection in canines.

Dynamic changes in cerebral microcirculation and hypoxia in the early stages of diffuse axonal injury

This study demonstrated that damage to the cerebral microvasculature, the formation of microthrombi and swelling of vascular endothelial cells occur early and peak 12 hours after injury in a rat model of diffuse axonal injury. Moreover, these pathological changes were most evident in the cerebral cortex. Cerebral microcirculatory dysfunction peaked later and had a shorter duration than axonal injury. In addition, the radioactive imaging agent, 99Tcm-4, 9-diaza-2, 3, 10, 10- tetramethyldodecan-2, 11 -dione dioxime, was used to visualize the dynamic changes that occur in tissue with cerebral hypoxia. The results demonstrated that cerebral hypoxia occurs at an early stage in diffuse axonal injury. Cerebral hypoxia was evident 12 hours after injury and declined slightly 24 hours after injury, but was significantly higher than in the control group. The pathological changes that underpin microcirculatory dysfunction did not occur at the same time as axonal injury, but did occur simultaneously with neuronal injury. Cerebral hypoxia plays a key role in promoting the secondary brain injury that occurs after diffuse axonal injury.

MiRNA-429 suppresses the growth of gastric cancer cells in vitro

Micro-RNAs（miRNAs） have been found to be implicated in a very wide range of physiological processes.This study was aimed to investigate the regulation of miRNA-429（miR-429） in gastric cancer cells on cell proliferation and apoptosis.Quantitative PCR was employed to detect the expressions of miR-429 after eukaryotic expression plasmid of miR-429 and its inhibitor were transiently transfected into poorly differentiated human gastric can-cer cell line BGC823.The 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） reduction as-says were used to examine proliferation ability.Apoptosis was analyzed by flow cytometry after transfection.The results showed that 48 h after transfection,overexpression of miR-429 reached maximum efficiency.Compared with mock transfection,miR-429 inhibited tumor cell proliferation significantly（P 〈 0.05） at 48 h and 72 h.of Overexpression of miR-429 promoted tumor cell apoptosis when compared with mock transfected cells（P 〈 0.05）.On the contrary,miR-429 inhibitor promoted tumor cell proliferation and inhibited apoptosis when compared with controls（P 〈 0.05）.Our results suggested that miRNA-429 may serve as a tumor suppressor during tumorigenesis of gastric cancer and may be a potential gastric cancer therapeutic target.

siRNA directed against TrkA sensitizes human pancreatic cancer cells to apoptosis induced by gemcitabine through an inactivation of PI3K/Akt-dependent pathway

Objective To determine the effect of suppressing TrkA expression on pancreatic cancer chemosensitivity to gemcitabine and further disclose the role of PI3K/Akt signal transduction pathway in pancreatic cancer chemoresistance.Methods Human pancreatic cancer cell lines PANC-1,MIA-PaCa2 and ASPC-1 were studied.The expression and kinase activity of TrkA were determined by Western blot analysis and in vitro kinase assay,respectively.RNA interference was used to suppress TrkA expression.Gemcitabine-induced cytotoxicity was determined by tetrazolium reduction assay and caspase profiling was performed.The effect of TrkA-specific siRNA on PI3K/Akt activity was also quantified.Results TrkA expression and kinase activity in cell lines were directly correlated with gemcitabine chemoresistance.TrkA-specific siRNA suppressed TrkA expression and kinase activity,and furthermore increased gemcitabine-induced,caspase-mediated apoptosis.PI3K/Akt activity was decreased by suppression of TrkA expression.Conclusion TrkA is a determinant of pancreatic adenocarcinoma chemoresistance and PI3K/Akt is a key signaling component by which NGF activation of the TrkA signal transduction pathway protects pancreatic cancer cells from chemotherapy-induced cell death.

An optimal dose of tea polyphenols protects against global cerebral ischemia/reperfusion injury

Previous studies addressing the protection of tea polyphenols against cerebral ischemia/ reperfusion injury often use focal cerebral ischemia models, and the optimal dose is not unified. In this experiment, a cerebral ischemia/reperfusion injury rat model was established using a modified four-vessel occlusion method. Rats were treated with different doses of tea polyphenols （25, 50, 100, 150, 200 mg/kg） via intraperitoneal injection. Results showed that after 2, 6, 12, 24, 48 and 72 hours of reperfusion, peroxide dismutase activity and total antioxidant capacity in brain tissue gradually increased, while malondialdehyde content gradually decreased after tea polyphenol intervention. Tea polyphenols at 200 mg/kg resulted in the most apparent changes. Terminal deoxynucleotidyl transferase-mediated nick end labeling and flow cytometry showed that 200 mg/kg tea polyphenols significantly reduced the number and percentage of apoptotJc cells in the hippocampal CA1 region of rats after cerebral ischemia/reperfusion injury. The open field test and elevated plus maze experiments showed that tea polyphenols at 200 mg/kg strengthened exploratory behavior and reduced anxiety of cerebral ischemia/reperfusion injured rats. Experimental findings indicate that tea polyphenols protected rats against cerebral ischemia/ reperfusion injury and 200 mg/kg is regarded as the optimal dose.

Effects of transforming growth factor β2 and connective tissue growth factor on induction of epithelial mesenchymal transition and extracellular matrix synthesis in human lens epithelial cells

AIM:To Investigate the effects of transforming growth factorβ2(TGF-β2)and connective tissue growth factor(CTGF)on transdifferentiation of human lens epithelial cells(HLECs)cultured in vitro and synthesis of extracellular matrix(ECM).METHODS:HLECs were treated with TGF-β2(0,0.5,1.0,5,10μg/L)and CTGF(0,15,30,60,100μg/L)for different times(0,24,48,72h)in vitro and the expression ofα-smooth muscle actin(α-SMA),the main component of the extracellular matrix typeⅠcollagen(Col-1)and fibronectin(Fn)were measured by using real-time polymerase chain reaction(PCR)and western-blot.RESULTS:TGF-β2 and CTGF significantly increased expression ofα-SMA mRNA and protein(P【0.05,P【0.001),Fn mRNA and protein(P【0.001),Col-1 mRNA and protein(P【0.001).TGF-β2 could induce HLECs expression of CTGF mRNA and protein in dosedependent manner(P【0.05,P【0.001).TGF-β2 and CTGF could induce HLECs to expressα-SMA,Fn and Col-1 in time-dependent manner.Each time of TGF-β2and CTGF induced HELCs expression ofα-SMA,Fn,Col-1 mRNA and protein was significant increase compared with control(P【0.05,P【0.001).CONCLUSION:TGF-β2 and CTGF could induce HLECs epithelial mesenchymal transition and ECM synthesis.

MiR-210 expression reverses radioresistance of stem-like cells of oesophageal squamous cell carcinoma

AIM: To investigate the expression of miR-210 and the role it plays in the cell cycle to regulate radioresistance in oesophageal squamous cell carcinoma(ESCC). METHODS: Mi R-210 expression was evaluated in 37 pairs of ESCC tissues and matched para-tumorous normal oesophageal tissues from surgical patients who had not received neoadjuvant therapy, and in the cells of two novel radioresistant cell lines, TE-1R and Eca-109 R, using quantitative reverse transcription-polymerase chain reaction(q RT-PCR). The transient up-regulation of mi R-210 expression in TE-1R and Eca-109 R cells was studied using liposomes and was confirmed using qR T-PCR. The rate of cell survival after a series of radio-treatment doses was evaluated using the cloneformation assay. Flow cytometry was used to detect the changes to the cell cycle patterns due to radiation treatment. RT-PCR and Western blot were used to detect the expression of ataxia telangiectasia mutated(ATM) and DNA dependent protein kinase(DNA-PKcs) after irradiation, and the cell sphere formation assay was used to evaluate the proliferative ability of the cancer stem-like cells.RESULTS: The level of mi R-210 expression was significantly decreased, by 21.3% to 97.2%, with the average being 39.2% ± 16.1%, in the ESCC tissues of most patients(81.1%, 30 of 37 vs patients with high mi R-210 expression, P < 0.05). A low level of expression of miR-210 was correlated with a poorly differentiated pathological type(P < 0.01) but was not correlated with the T-stage or lymph node infiltration(both P > 0.05). Early local recurrences(< 18 mo, n = 19) after radiotherapy were significantly related with low miR-210 expression(n = 13, P < 0.05). The level of mi R-210 was decreased by approximately 73%(vs TE-1, 0.27 ± 0.10, P < 0.01) in the established radioresistant TE-IR cell line and by 52%(vs Eca-109, 0.48 ± 0.17, P < 0.05) in the corresponding Eca-109 R line. Transient transfection with a mi R-210 precursor increased the level of mi R-210 expression, leading to a significant increase in cell survival after radiotherapy(P < 0.05). Twenty-four hours after radiation, the proportion of pmiR-210 cells in S phase was increased(vs control cells, 30.4% ± 0.4%, and vs untreated TE-1R cells, 23.3% ± 0.7%, P < 0.05 for both). The levels of DNA-PKcs(0.21 ± 0.07) and ATM(0.12 ± 0.03, P < 0.05) proteins were significantly lower in the PmiR-210 cells than in control cells, but no differences were found in the levels of the corresponding mR NAs in the two cell types(P > 0.05 for all). Exogenous mi R-210 expression decreased the diameter of pmi R-210 cell spheres(vs control cells, 0.60 ± 0.14, P < 0.05).CONCLUSION: Mi R-210 expression is negatively correlated with the pathological type and the local survivalrate after radiotherapy, and high expression of miR-210 may reverse the radioresistance of ESCC stem-like cells.

Combined treatment of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer

AIM:To investigate the efficacy and side effects of the combined therapy of oxaliplatin and capecitabine in patients with metastatic esophageal squamous cell cancer(ESCC) and the survival of the patients.METHODS:Sixty-four patients(median age of 63 years) with histological or cytological confirmation of ESCC received oxaliplatin 120 mg/m2 intravenously on day 1 and capecitabine 1000 mg/m2 orally twice daily on days 1 to 14 in a 21-d treatment cycle as palliative chemotherapy.Each patient received at least two cycles of treatment.The efficacy,side effects and patient survival were evaluated.RESULTS:The partial response(PR) rate was 43.8%(28/64).Stable disease(SD) rate was 47.9%(26/64),and disease progression rate was 15.6%(10/64).The clinical benefit rate(PR + SD) was 84.4%.The main toxicities were leukopenia(50.0%),nausea and vomiting(51.6%),diarrhea(50.0%),stomatitis(39.1%),polyneuropathy(37.5%) and hand-foot syndrome(37.5%).No grade 4 event in the entire cohort was found.The median progression-free survival was 4 mo,median overall survival was 10 mo(95% CI:8.3-11.7 mo),and the 1-and 2-year survival rates were 38.1% and 8.2%,respectively.High Karnofsky index,single metastatic lesion and response to the regimen indicated respectively good prognosis.CONCLUSION:Oxaliplatin plus capecitabine regimen is effective and tolerable in metastatic ESCC patients.The regimen has improved the survival moderately and merits further studies.

Abrupt onset of type 1 diabetes mellitus during recombinant interferon-alpha 2b therapy in a patient with chronic hepatitis B

We describe a case of a 33-year-old female patient with chronic hepatitis B who developed type 1 diabetes mellitus (DM) after a 13-mo period of treatment with recombinant human interferon-alpha (IFN-α) 2b. The patient presented with polydipsia, polyuria, hypergly-cemia, diabetic ketoacidosis, combined with C-peptide secretion defi ciency and positive islet cell autoantibody (ICAb). IFN-α 2b treatment was terminated and in-stead insulin treatment was initiated. Five months after cessation of the recombinant human IFN-α 2b therapy, the patient remained insulin-dependent. Her serum HBV DNA became negative and serum transaminase returned to the normal level after a 10-mo period of IFN therapy. Type 1 DM induced by IFN-α is relatively rare in patients with chronic hepatitis B. We should pay more attention to patients on IFN-α therapy to avoid destruction of pancreatic beta cells. This is the first case report from China.

Magnetic resonance cholangiopancreatography for the detection of pancreatic duct stones in patients with chronic pancreatitis

AIM:To assess the role of magnetic resonance cholangiopancreatography(MRCP) in detection of pancreatic duct stones(PDS) in patients with chronic pancreatitis(CP).METHODS:Clinical data of 78 CP patients who were treated at the First Affi liated Hospital of Xi'an Jiaotong University(China) between January 2004 and July 2008 were retrospectively analyzed.A predictive model of pancreatic duct stones was established through logistic regression and its effectiveness was verifi ed.Among these patients, MRCP was performed in 60 patients who served as a control group, while 44 patients with a higher predictive value than the entry threshold of the predictive model served as an experimental group.RESULTS:The positive rate of PDS in the 78 patients with CP was 19.2%(15/78).The predictive entry threshold of the predictive model was 5%(P < 0.05).The possibility of existence of PDS could be predicted according to the following 4 indexes:gastrointestinal symptoms, intermittent abdominal pain, diabetes mellitus(DM)/impaired glucose tolerance(IGT) and positive B-mode ultrasound results.The incidence of PDS in the experimental group was higher than that in the control group(P < 0.05).CONCLUSION:MRCP is strongly suggested for the detection of PDS in patients with gastrointestinal symptoms, intermittent abdominal pain, DM/IGT and positive B-mode ultrasound results.

Methylation status of the interferon-gamma gene promoter in chronic hepatitis B

Objective To evaluate the methylation status at CpG site -55 in the interferon-gamma (IFN-γ) gene promoter and its effect on IFN-γ expression in chronic hepatitis B. Method The authors recruited 30 patients with HBeAg-positive chronic hepatitis B (CHB), 30 HBeAg-negative CHB patients, and 30 healthy blood donors. Pyrosequencing was used to determine the methylation status at CpG site -55 in the IFN-γ gene promoter following bisulfite treatment of DNA in peripheral blood mononuclear cells (PBMCs). The expression of IFN-γ was analyzed by real-time RT-PCR and ELISA. HBV DNA in PBMCs was detected by nested PCR. Results The methylation level at CpG site -55 in the IFN-γ gene promoter was significantly increased, resulting in subsequent down-regulation of the expression of this cytokine in CHB. The methylation level at CpG site -55 was significantly higher in HBeAg-positive patients than in HBeAg-negative ones (P<0.01) and was also significantly higher in PBMCs from HBV DNA-positive patients than from HBV DNA-negative ones (P<0.01); the methylation level at CpG site -55 was positively correlated with the amount of HBV DNA in serum (P<0.01). Conclusion IFN-γ gene expression appears to be regulated by methylation of the IFN-γ gene promoter in CHB; the methylation level at CpG site -55 is associated with HBV infection.

Olfactory ensheathing cell transplantation for spinal cord injury An 18-year bibliometric analysis based on the Web of Science

OBJECTIVE： Olfactory ensheathing cell （OEC） transplantation is a promising new approach for the treatment of spinal cord injury （SCI）, and an increasing number of scientific publications are devoted to this treatment strategy. This bibliometric analysis was conducted to assess global research trends in OEC transplantation for SCI. DATA SOURCE： All of the data in this study originate from the Web of Science maintained by the Institute for Scientific Information, USA, and includes SCI-EXPANDED, SSCI, A＆HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, CCR-EXPANDED and IC. The Institute for Scientific Information＇s Web of Science was searched using the keywords ＂olfactory ensheathing cells＂ or ＂OECs＂ or ＂olfactory ensheathing gila＂ or ＂OEG＂ or ＂olfactory ensheathing glial cells＂ or ＂OEGs＂ and ＂spinal cord injury＂ or ＂SCI＂ or ＂spinal injury＂ or ＂spinal transection＂ for literature published from January 1898 to May 2012. DATA SELECTION： Original articles, reviews, proceedings papers and meeting abstracts, book chapters and editorial materials on OEC transplantation for SCI were included. Simultaneously, unpublished literature and literature for which manual information retrieval was required were excluded. MAIN OUTCOME MEASURES： All selected literatures addressing OEC transplantation for SCI were evaluated in the following aspects： publication year, document type, language, author, institution, times cited, Web of Science category, core source title, countries/territories and funding agency.RESULTS： In the Web of Science published by the Institute for Scientific Information, the earliest literature record was in April, 1995. Four hundred and fourteen publications addressing OEC transplantation for SCI were added to the data library in the past 18 years, with an annually increasing trend. Of 415 records, 405 publications were in English. Two hundred and fifty-nine articles ranked first in the distribution of document type, followed by 141 reviews. Thirty articles and 20 reviews, cited more than 55 times by the date the publication data were downloaded by us, can be regarded as the most classical references. The journal Experimental Neurology published the most literature （32 records）, followed by Glia. The United States had the most literature, followed by China. In addition, Yale University was the most productive institution in the world, while The Second Military Medical University contributed the most in China. The journal Experimental Neurology published the most OEC transplantation literature in the United States, while Neural Regeneration Research published the most in China. CONCLUSION： This analysis provides insight into the current state and trends in OEC transplantation for SCI research. Furthermore, we anticipate that this analysis will help encourage international cooperation and teamwork on OEC transplantation for SCI to facilitate the development of more effective treatments for SCI.

Whole-cell recordings of calcium and potassium currents in acutely isolated smooth muscle cells

AIM： To record calcium and potassium currents in acutely isolated smooth muscle cells of mesenteric arterial branches in rats. METHODS： Smooth muscle cells were freshly isolated by collagenase digest and mechanical trituration with polished pipettes. Patch clamp technique in whole-cell mode was employed to record calcium and potassium currents. RESULTS： The procedure dissociated smooth muscle cells without impairing the electrophysiological characteristics of the cells. The voltage-gated Ca^2＋ and potassium currents were successfully recorded using whole-cell patch clamp configuration. CONCLUSION： The method dissociates smooth muscle cells from rat mesenteric arterial branches. Voltage-gated channel currents can be recorded in this preparation.

Effect of ziprasidone on QTc interval in Chinese patients with schizophrenia

Objective： To investigate the effect of ziprasidone on QTc in Chinese patients with schizophrenia. Methods： The study involved 27 patients with schizophrenia. Ziprasidone was initiated with 40 mg/day. From day 3 to day 7, the dose was increased gradually to 120-160 mg/d according to the effectiveness and tolerahility. QTc values were measured at the beginning and month 6. Results： At the beginning of the 6 months treatment, the mean QTc interval of patients was （387.5±19.0） ms. At the end of the study, it was （402.9±23.6） ms. The difference has statistically significance （P〈0.05）. The mean QTc interval changed significantly throughout 6-months period but no one exceed the QTc dangerous limits. Significant correlation was found between QTc interval and the dose. Conclusion： In summary, our results suggest that ziprasidone has good tolerance in patient with schizophrenia despite its dose-related QTc prolongation. Ziprasidone have no pro-arrhythmic profile

Effects of HSP70 Antisense Oligonucleotide on the Proliferation and Apoptosis of Human Hepatocellular Carcinoma Cells

The study investigated the effects of heat shock protein 70(HSP70) antisense oligonucleotide(ASODN) on the proliferation and apoptosis of a human hepatocellular carcinoma cell line(SMMC-7721 cells) in vitro.HSP70 oligonucleotide was transfected into SMMC-7721 cells by the mediation of SofastTM transfection reagent.Inhibition rate of SMMC-7721 cells was determined by using MTT method.Apoptosis rate and cell cycle distribution were measured by flow cytometry.Immunocytochemistry staining was used to observe the expression of HSP70,Bcl-2 and Bax.The results showed that HSP70 ASODN at various concentrations could significantly inhibit the growth of SMMC-7721 cells,and the inhibition effect peaked 48 h after transfection with 400-nmol/L HSP70 ASODN.Cytometric analysis showed the apoptotic rate was increased in a dose-and time-dependent manner in the HSP70 ASODN-treated cells.The percentage of cells in the G2/M and S phases was significantly decreased and that in the G0/G1 phase increased as the HSP70 ASODN concentration was elevated and the exposure time prolonged.Immunocytochemistry showed that treatment of SMMC-7721 cells with HSP70 ASODN resulted in decreased expressions of HSP70 and Bcl-2 proteins,and an increased expression of Bax protein.It was concluded that the HSP70 ASODN can inhibit the growth of the SMMC-7721 cells and increase cell apoptosis by down-regulating the expression of HSP70.HSP70 ASODN holds promise for the treatment of hepatocellular carcinoma.

Randomized trial of weekly docetaxel and cisplatin combined with concurrent 3DCRT in patients with locally advanced esophageal cancer

Abstract Objective： This randomized controlled clinical study was to assess and compare the efficacy and safety of two chemoradiotherapy regimens [cisplatin ＋ 5-fluorouracil ＋ 3 dimensional conformal radiation therapy （3DCRT） and cisplatin ＋ weekly docetaxel ＋ 3DCRT] in patients with locally advanced esophageal squamous cell carcinoma. Methods： A total of seventy-four patients with clinical stages liB to IIIB esophageal squamous cell carcinoma were enrolled. Chemotherapy for PF group comprised 5-fluorouracil at days 1-5 （250 mg/m2/d） and cisplatin （20 mg/m2） at days 1-3 of every 28-day cycle; full treatment course included 2 cycles. Chemotherapy for DP group comprised docetaxel （20 mg/m2） and cisplatin （20 mg/m2） at days 1,8, 15, 22, 29, and 36. Both groups treated with concurrent 60 Gy 3DCRT at 200 cGy/d. Results： Seventy-four patients were enrolled and 71 completed the planned treatment, with a follow-up rate of 95.94%. Short-term curative effect was not statistically significant between the two groups （P = 0.471）. The 2-year survival rates were 65.7% and 61.1%, respectively （P = 0.806）, 5 years survival rates were 34.29% and 27.78%, respectively （P = 0.221）, and there was no significant difference by Fisher test （P = 0.734）. As common side effects, incidence rates of radioactive esophagitis and hematological toxicity were lower in DP group. Conclusion： For locally advanced esophageal cancer patients, current chemoradiotherapy with chemo- therapy regimen of weekly docetaxel plus cisplatin has equal curative effect with 5-fluorouracil plus cisplatin, but well-tolerated by reducing side effects such as radioactive esophagitis and bone marrow suppression.

The clinical value of enzyme-multiplied immunoassay technique monitoring the plasma concentrations of cyclosporine A after renal transplantation

The feasibility and the clinical value of the enzyme-multiplied immunoassay technique （EMIT） monitoring of blood concentrations of cyclosporine A （CsA） in patients treated with CsA were investigated after kidney transplantation. The validation method was performed to the EMIT determination of CsA blood concentration, the CsA whole blood trough concentrations （Co） of patients in different time periods after renal transplantation were monitored, and combined with the clinical complications, the statistical results were analyzed and compared. EMIT was precise, accurate and stable, also with a high quality control. The mean postoperative blood concentration of CsA was as follows： 〈1 month, （281.4± 57.9）ng/mL; 2 - 3 months, （264.5 ± 41.2） ng/mL; 4 - 5 months, （236.4 ± 38.9） ng/mL; 6 - 12 months, （206.5± 32.6）ng/mL; 〉12 months, （185.6± 28.1）ng/mL. The toxic reaction rate of CsA blood concentration within the recommended therapeutic concentration was 14.1%, significantly lower than that of the none-recommended dose group （37.2%） （P〈0.05）; the transplantation rejection rate was 4.4%, significantly lower than that of the none- recommended dose group （22.5%） （P〈0.05）. Using EMIT to monitor the blood concentration of CsA as the routine laboratory method is feasible, and is able to reduce the CsA toxicity and rejection significantly, leading to achieving the desired therapeutic effect.