Gaucher disease is a commonly inherited, autosomtic recessive lysosomal storage disorder, due to the mutation of structure gene encoding beta-glucocerebrosidase (GC) resulted in the deficiency of the enzyme. Besides enzyme replacement, there is no good ways to treat it. This review briefly introduced the phenotypes, pathologic physiology and general therapy to the disease, strongly stress the genetherapy. From animals to human, from in vitro to in vivo, the review detaily descibe the rapid progress made in genetherapy of Gaucher disease.

Objective To investigate the significance of Th 17 cells, Treg cells and Th17/Treg cell-associated cytokines in the development of tuberculous pleurisy through detecting the expressions of Th 17 cells and Treg cells (CD4+CD25+Foxp3+) in CD4+T cells, analyzing concentrations of IL-17, IL-23, IL-6 and TGF-βin serum of patients with tuberculous pleurisy and healthy controls and measuring levels of IL -17, IL-23, IL-6 and TGF-βin hydrothorax of patients with tuberculous pleurisy .Methods Flow cytometry was used to detect expressions of Th 17 and Treg cells in peripheral blood of patients with tuberculous pleurisy and healthy controls.ELISA method was performed for quantitative detection of concentrations of IL -17, IL-23, IL-6 and TGF-βin serum and hydrothorax .Differences and correlations between the above measured data were analyzed by the statistical software SPSS 17.0.Results Compared with the healthy control group , the expressions of Th17 cells in peripheral blood of the patients were significantly increased (1.02%±0.20%vs.0.89%±0.13%, P=0.002<0.05), while the expressions of Treg cells were significantly decreased (4.64%±0.77%vs.5.10%±0.90%, P=0.000<0.05).Correspondingly, the ratio of Th17/Treg cells (0.25±0.07) in the patients were significantly higher than that in the healthy controls (0.17±0.05, P=0.000<0.05).Concentrations of IL-17, IL-23 and IL-6 in peripheral blood and in hydrothorax of the pa-tients were (17.49±3.94) ng/L, (90.42±23.06) ng/L, (4.54±1.02) ng/L and (26.13±5.98) ng/L, (122.26±31.71) ng/L, (5.31±0.74) ng/L respectively, which were remarkably higher than the levels of IL-17 (14.45±3.81) ng/L, IL-23 (77.55±20.26) ng/L and IL-6 (4.26±0.91) ng/L in control group. In tuberculous pleurisy group , concentrations of IL-17, IL-23 and IL-6 in hydrothorax were significantly higher than those in peripheral blood with P values of 0.000, 0.000 and 0.003.There was no difference be-tween IL-6 levels in peripheral blood from patients and IL-6 levels in peripheral blood from the healthy con-trols, P=0.274.In comparison with the control group , TGF-βlevels in peripheral blood and in hydrothorax of the patients were significantly decreased (3.95 ng/L±0.79 ng/L, 3.12 ng/L±0.77 ng/L vs.3.32 ng/L ±0.80 ng/L) .In tuberculous pleurisy patients , the expression of Th17 cells in peripheral blood was nega-tively correlated with Treg cells in peripheral blood (r=-0.684, P=0.000<0.05), but was positively relat-ed to the levels of IL-17, IL-23 and IL-6 (r=0.479, 0.441, 0.326, P=0.013, 0.015, 0.017).TGF-βlevel had significantly positive correlations with Treg cells in the peripheral blood of the patients (r=0.297, P=0.024), but no significant correlation with Th17 cells was found (r=0.091, P=0.659).Conclusion Th17/Treg cell-associated cytokines might regulate the expressions of Th 17 and Treg cells and inflammatory reaction.Changes of Th17 cells, Treg cells and related cytokines might be important immunopathological mechanisms for tuberculous pleurisy .

Objective To evaluate the clinical value of elasticity imaging and area ratio by ultrasonography in differential diagnosis of benign and malignant thyroid nodules.Methods Gray-scale ultrasound and elasticity imaging was used to examine 88 patients with thyroid nodules.The elasticity classification and area ratio were retrospectively reviewed and compared with pathology.The elasticity grades 1 - 3 predicted benign,grades 4 - 5 predicted malignant.Results Eighty-eight patients with 116 thyroid nodules were detected,93 nodules were benign and 23 nodules were malignant.( 1 )An elasticity grades of 1 - 3 was observed in 82 (95.3％) of 86 benign nodules,while elasticity grades of 4 - 5 in 19 (63.3％) of 30 malignant nodules.The diagnosis sensitivity,specificity and accurate rate of the elasticity grades was 82.6％,88.2％,87.1％.(2) The mean of elasticity imaging and area ratio of 93 benign nodules (1.31 ± 0.13 ) was statistically lower than that in 23 malignant nodules ( 1.73 ± 0.13 ) (t =13.536,P =0.001 ).( 3 )According to ROC analysis,the cut-off point of elasticity imaging and area ratio was determined as 1.52.With elasticity imaging and area ratio ＜ 1.52,89 nodules [98.9％(89/90)] were confirmed as benign and 22 nodules [84.6％ (22/26)] were confirmed as malignant by pathology.The diagnosis sensitivity,specificity and accurate rate of elasticity imaging and area ratio was 95.7％,95.7％,95.7％.(4)The area under the ROC curve of elasticity imaging and area ratio ≥ 1.52 was 0.996,significantly higher than that of elasticity grades ≥ 4 (0.891).The diagnostic accurate rate of elasticity imaging and area ratio was significantly higher than that of elasticity grades(95.7％ vs.87.1％,x2 =5.472,P=0.019).Conclusions The elasticity imaging and area ratio by ultrasonography can be used in the differential diagnosis of thyroid lesions.It is a new diagnostic indicator for diagnosis of thyroid lesions.

Objective To explore the effects of piperine on cell proliferation and migration in angiotensin Ⅱ (Ang Ⅱ)-treated rat airway smooth muscle cells (ASMCs).Methods The primary ASMCs of rats were cultured by improved tissue-piece digestion inoculation and trypsin digestion.MTT assay was used to detect the effects of Ang Ⅱ and Ang Ⅱ receptor antagonist losartan on cell proliferation activity.After treatment with Ang Ⅱ and piperine, the cell proliferation activity, the cell cycle distribution and the cell migration were detected by MTT, flow cytometry and Transwell assay respectively.ERK1/2 inhibitor PD98059 and losartan were then applied to determine the expression of cyclin D1, MMP-9, p-ERK1/2, ERK1/2, and β-actin proteins by Western blot assay.Results After 24 h culture, Ang Ⅱ treatment promoted the cell proliferative activity in rat ASMCs (P<0.05), and the promotive effect of 10-7 mol/L Ang Ⅱ was the most significant.Additionally, losartan blocked the Ang Ⅱ-induced cell proliferative activity in rat ASMCs (P<0.05).10-7 mol/L Ang Ⅱ treatment resulted in the elevated cell proliferative activity, higher S phase fraction, increased migrated cell number, and enhanced expression of cyclin D1, MMP-9and p-ERK1/2 proteins (P<0.05);these effects were dose-dependently reversed by piperine.Both PD98059 and losartan blocked Ang Ⅱ-induced expression of p-ERK1/2, cyclin D1 and MMP-9 proteins in rat ASMCs.Conclusions Piperine may inhibit Ang Ⅱ-induced cell proliferation and cell migration via ERK1/2 signaling pathway in rat ASMCs.

[ ABSTRACT] AIM:To investigate the effects of sulindac on oxidative stress in autism.METHODS:With an au-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of canonical Wnt pathway in the prefrontal cortex ( PFC) and hippocampus ( HC) of autistic rats treated with sulindac.The protein expression levels of glycogen synthase kinase 3β(GSK-3β), β-catenin and 4-hydroxynonenal (4-HNE) were ob-served by Western blotting.The mRNA expression of thioredoxin(Trx)1 and Trx2 was assessed by semi-quantitative RT-PCR.RESULTS:The protein level of GSK-3βand mRNA levels of Trx1 and Trx2 were lower, whereas the protein expres-sion levels ofβ-catenin and 4-HNE were higher in VPA group than those in control group.In contrast, the protein levels of GSK-3βwere significantly higher in the animals treated with both VPA and sulindac than those in VPA group, while the lev-els ofβ-catenin and 4-HNE were decreased.CONCLUSION:Sulindac attenuates oxidative stress in the pathogenesis of au-tism, suggesting the up-regulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and further facili-tates susceptibility to autism.

Objective To study the diagnosis and treatment of omental torsion.Methods 73 patients with omental torsion from Jan 1995 to Dec 2009 in literatures together with the one we reported were reviewed and analyzed The range of ages was from 3 to 65 years,and the median age was 25.3 years.Among them,35 cases were less than 18 years old(47%,and 27 with obesity) and others more than 18 years old(53%,1 with obesity).The accurate diagnosis before operation exsited in 9 patients.49 patients(66%) were diagnosed as primary omental torsion,and childhood obesity was the most related factor.Conversely,25(34%) were diagnosed as secondary omental torsion,while the most common reason was adhersion.In contrast with other clinical symotoms and signs,abdominal pain and tenderness were occurred in almost every people.Bultro sonography(positive rate:24%,6/25) was hardly useful in diagnosis but CT (positive rate:96%,23/24) and MRI(positive rate:100%,2/2) were beniticial.Operation was applied in all patients,while laparoscopy was uesed in 23 patients.As a rule,the appendix was removed together in 61 persons.The cobort of patients was recoverd fully without serious complications such as hemorrhage and intestinal infarction.Conclusion Omental torsion was a relatively rare disease,and the diagnosis should be easy with the help of CT and MRI,and the laparoscopy was the better choice for surgeons.

Objective To observe the effects of hedysari polysaccharide (HPS) on myocardial fibrosis and the expression of MMP-2/TIMP-2 in model mice of diabetic cardiomyopathy; To discuss the mechanism of action of prevention and treatment of myocardial fibrosis in diabetes.Methods Sixty mice were randomly divided into model group, rosiglitazone group and HPS high-, mediume- and low-dose groups. The normal group was 12 non-transgenic male BKS.Cg-Dock7m+/+Leprdb/JNjumice with the same age. Each group was given relevant medicine for gavage, for 8 weeks. Blood glucose of mice before and after medication 2, 4, 6, and 8 weeks was detected. The levels of MMP-2, MMP-2 and MMP-9 in myocardium were measured by Masson staining. The protein expressions of MMP-2 and TIMP-1 in myocardium were detected by Western blot.Results Compared with the model group, the blood glucose of HPS (high- and medium dose) groups and rosiglitazone group decreased significantly. Masson staining showed that the green fibers in the model group significantly increased and rosiglitazone group and HPS high-dose group decreased compared with the model group. Western blot showed that the expressions of MMP-2 in model group and MMP-2/TIMP-2 ratio were declined significantly, while the expression of MMP-2 was increased and TIMP-2 was decreased significantly, and the ratio of MMP-2/TIMP-2 increased in rosiglitazone group and HPS high- and medium-dose group.Conclusion HPS may reduce the degree of myocardial fibrosis in model mice with diabetic cardiomyopathy. The therapeutic effect of HPS may be to relieve myocardial fibrosis in model mice by increasing the ratio of MMP-2/TIMP-2.

BACKGROUND:Bone marrow mesenchymal stem cel transplantation has not been thoroughly reported on its effects on apoptosis in hepatoma carcinoma cel s and inflammatory factor level.
OBJECTIVE:To investigate the effect of rat bone marrow mesenchymal stem cel s on dynamic change of inflammatory factors and cel apoptosis during hepatocarcinogenesis.
METHODS:Sixty healthy Sprague-Dawley rats were divided randomly into healthy group (n=30), control group (n=30) and transplantation group (n=30). Healthy group was given ordinary feed and normal water, while other groups were given diethylnitrosamine solution in drinking water to induce liver cancer models. Then, rats in the transplantation group were subjected to bone marrow mesenchymal stem cel transplantation via the tail vein. Two weeks after cel transplantation, CXCL5, interleukin-8 and interleukin-6 levels were tested by ELISA, mRNA level of hepatocyte nuclear factor 1αdetected by RT-PCR, expression of Bcl-2 and Bax in liver tissue measured by immunohistochemical method, and liver cancer cel apoptosis index detected by TUNEL technique.
RESULTS AND CONCLUSION:After modeling, the expressions of CXCL5, interleukin-8 and interleukin-6 in the control group were significantly higher than those in the healthy group (P<0.05), while these indexes were reduced significantly after bone marrow mesenchymal stem cel transplantation (P<0.05) and close to the normal levels (P>0.05). Bone marrow mesenchymal stem cel transplantation significantly up-regulated the mRNA level of hepatocyte nuclear factor 1αin the liver tissue that was decreased obviously after modeling (P<0.05). In addition, the expression of Bcl-2 was reduced, while the expression of Bax and the apoptosis index increased significantly in the transplantation group compared with the control group (P<0.05). These findings indicate that bone marrow mesenchymal stem cel transplantation contributes to hepatocyte differentiation and regeneration in liver cancer rats by reducing serum inflammatory factor levels and promoting apoptosis in hepatoma carcinoma cel s.

OBJECTIVE:To prepare transferrin modified paclitaxel-loaded liposome(TF-PTX-LP),and to study the tumor in-hibition effect. METHODS:TF-PTX-LP was prepared by thin-film method,and morphology of TF-PTX-LP was observed. Qualita-tive and quantitative investigation were used to value the uptake efficiency of TF-LP and LP by HepG2 cells. The proliferation inhi-bition rate of HepG2 cells was investigated after treated with PTX,PTX-LP and TF-PTX-LP for 24,48 and 72 h. Tumor spheres were prepared by using HepG2 cells. Effects of normal saline,PTX,PTX-LP and TF-PTX-LP on the volume of tumor spheres were investigated after 0,1,2,4,5,6 and 7 d treatment. HepG2 tumor-bearing nude mice model was induced. Inhibitory effects of normal saline,PTX,PTX-LP and TF-PTX-LP(8.5 mg/kg by PTX)on transplantable tumor of tumor-bearing nude mice were in-vestigated. RESULTS:TF-PTX-LP showed uniform spherical shape,with particle size of 100-120 nm. The fluorescence intensity of HepG2 cells treated with TF-LP was stronger than that treated with LP(P<0.01). Compared with PTX and PTX-LP,TF-PTX-LP showed higher proliferation inhibition rate(P<0.01). Compared with normal saline,PTX and PTX-LP,tumor spheres were small-er in volume after treated with TF-PTX-LP,and inhibition rate of tumor was higher in tumor-bearing nude mice;there were statisti-cal significance after treated for 6,7 d(P<0.01). The proliferation inhibition rate and tumor spheres volume changed in time-de-pendent manner. CONCLUSIONS:TF-PTX-LP which owns good tumor inhibition effect is prepared successfully.

Objective To observe the efficacy and side effects of anlotinib combined with paclitaxel and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma (ESCC). Methods We retrospectively analyzed 50 cases of advanced esophageal squamous cell carcinoma diagnosed pathologically. Among them, 24 cases were treated with the combination of anlotinib and paclitaxel plus cisplatin (experimental group), and 26 cases were treated with paclitaxel plus cisplatin regimen (control group). The efficacy and adverse reactions were observed and followed up. Results The objective response rates of the experimental and control groups were 83.33% and 53.84% (P < 0.05), the disease control rates were 100% and 96.15% (P > 0.05), mPFS were 10.6 and 9.13 months (P < 0.05), and mOS were 13.4 and 11.8 months (P < 0.05). The common adverse events in the experimental group were hand-foot syndrome (12.5%), hypertension (12.5%), epistaxis (8.33%) and proteinuria (4.16%), all of which were grade Ⅰ-Ⅱ and controllable without affecting the continuity of chemotherapy. Conclusion The combination of anlotinib, paclitaxel and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma can improve the curative effect and the adverse effects are endurable.