BACKGROUNDHereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasia, and arteriovenous malformations. The efficacy of traditional treatments for HHT is very limited. The aim of this study was to investigate the therapeutic role of thalidomide in HHT patients and the effect in FLI-EGFP transgenic zebrafish model.

METHODSHHT was diagnosed according to Shovlin criteria. Five HHT patients were treated with thalidomide (100 mg/d). The Epistaxis Severity Score (ESS), telangiectasia spots, and hepatic computed tomography angiography (CTA) were used to assess the clinical efficacy of thalidomide. The Fli-EGFP zebrafish model was investigated for the effect of thalidomide on angiogenesis. Dynamic real-time polymerase chain reaction assay, ELISA and Western blotting from patient's peripheral blood mononuclear cells and plasma were used to detect the expression of transforming growth factor beta 3 (TGF-β3) messenger RNA (mRNA) and vascular endothelial growth factor (VEGF) protein before and after 6 months of thalidomide treatment.

RESULTSThe average ESS before and after thalidomide were 6.966 ± 3.093 and 1.799 ± 0.627, respectively (P = 0.009). The "telangiectatic spot" on the tongue almost vanished; CTA examination of case 2 indicated a smaller proximal hepatic artery and decreased or ceased hepatic artery collateral circulation. The Fli-EGFP zebrafish model manifested discontinuous vessel development and vascular occlusion (7 of 10 fishes), and the TGF-β3 mRNA expression of five patients was lower after thalidomide therapy. The plasma VEGF protein expression was down-regulated in HHT patients.

CONCLUSIONSThalidomide reverses telangiectasia and controls nosebleeds by down-regulating the expression of TGF-β3 and VEGF in HHT patients. It also leads to vascular remodeling in the zebrafish model.

Animals ; Animals, Genetically Modified ; Female ; Green Fluorescent Proteins ; genetics ; metabolism ; Humans ; Middle Aged ; Telangiectasia, Hereditary Hemorrhagic ; drug therapy ; metabolism ; Thalidomide ; therapeutic use ; Transforming Growth Factor beta3 ; genetics ; Vascular Endothelial Growth Factor A ; metabolism ; Zebrafish

Objective To compare three different types of donor livers (C-Ⅰ,C-Ⅱ,C-Ⅲ) in clinical efficacy,complications and survival rate of liver transplantation.Methods Using the retrospective descriptive study method,the clinical data of 422 patients undergoing liver transplantation,including 124 cases of C-Ⅰ,81 cases of C-Ⅱ and 81 cases of C-Ⅲ in recent 6 years (from June 2010 to June 2016) were analyzed.The same surgical method was performed with piggyback liver transplantation.Observation indicators contained (1) recipient postoperative liver function;(2) the postoperative complications;(3) the recipient survival rate.SPSS 19.0 statistical software was used for analysis.Results (1) The curative effect was evaluated by the changes of ALT and TBIL among three groups of recipients postoperatively.As compared with C-Ⅰ transplantation group and CⅢ transplantation group,the level of ALT in C-Ⅱ transplantation group was significantly increased (P ＜0.05),the clinical efficacy was poorer.(2) The incidence of PNF was 3.23％ in C-Ⅰ group,9.88％ in C-Ⅱ group and 9.88％ in C-Ⅲ group (P＜0.05).The incidence of acute rejection was respectively 9.68％ in C-Ⅰ group,38.27％ in C-Ⅱ group and 38.27％ in C-Ⅲ group (P＜0.001).The incidence of SIRS was respectively 5.65％ in C-Ⅰ group,39.50％ in C-Ⅱ group and 39.50％ in C-Ⅲ group (P＜ 0.001).There were significant differences in the incidence of other complications among the three groups.(3) There were 14 deaths within 3 months,accounting for 17.28％,and the survival rate was 82.72％ in C-Ⅱ group,the 1-,3-,and 5-year survival rate was 76.55％,74.18％ and 76.55％ respectively in C-Ⅰ group,and that was 88.02％,85.72％ and 81.11％ respectively in C-Ⅲ group.Conclusion Since June 2015,C-Ⅰ donors grow up more quickly on year-on-year basis than C-Ⅱ.Simultaneously,the sort-term and long-term clinical efficacy is better in C-Ⅰ transplantation group than in C-Ⅱ transplantation group.How to repair the three types of Chinese standard donor organs and optimize the quality is still a hot point to ensure the healthy development of organ transplantation in China,which needs further investigation.

OBJECTIVETo observe the changes of sex hormones and sexual function in male patients with Graves' disease (GD) after Radioiodine-131 (I-131) therapy.

METHODSThirty-four male GD patients, aged 21 -40 (32.3 +/- 6.7) years, were treated with I-131 at the dose of 111 - 407 (237.8 +/- 51.8) MBq. The levels of serum sex hormones were measured, and the patients'scores on erectile function (IIEF-5) were obtained before and 3 and 6 months after the treatment. Another 20 healthy men aged 25 - 37 (31 +/- 3.1) years were enlisted as controls.

RESULTSThe baseline levels of estrogen (E2), testosterone (T) and luteinizing hormone (LH) were (132.5 +/- 40.4) pmol/L, (21.6 +/- 4.6) nmol/L and (10.1 +/- 4.4) IU/L in the GD patients, significantly higher than (80.4 +/- 31.2) pmol/L, (14.5 +/- 4.2) nmol/L and (6.2 +/- 1.9) IU/L in the healthy controls (P < 0.05). The E2, T and LH levels showed a significant decrease in the GD patients after 3 months of treatment ([110.2 +/- 20.6] pmol/L, [17.7 +/- 5.5] nmol/L and (9.4 +/- 3.9) IU/L, P < 0.05), but exhibited no statistically significant differences from the healthy controls at 6 months ([82.6 +/- 30.1] pmol/L, [13.8 +/- 3.4 ] nmol/L and [6.6 +/- 1.5] IU/L, P > 0.05). The IIEF-5 score of the GD patients was 5 - 25 (15.5 +/- 3.5) before I-131 treatment, significantly lower than that of the controls (19 - 25, 24 +/- 0.5) (P < 0.05), and it was 8 - 25 (19.5 +/- 1.0) at 3 months and 10 - 25 (23.5 +/- 1.5) at 6 months, significantly higher in the latter than in the former (P < 0.05), and with no significant difference between the 6-month treated patients and the healthy controls (P > 0.05).

CONCLUSIONThe E2, T and LH levels are increased while the IIEF-5 score decreased markedly in male GD patients. Six-month treatment with I-131 can not only restore the E2, T and LH levels to normal but also significantly improve the patient's sexual function.

Adult ; Case-Control Studies ; Estrogens ; blood ; Follicle Stimulating Hormone ; blood ; Graves Disease ; blood ; therapy ; Humans ; Iodine Radioisotopes ; therapeutic use ; Luteinizing Hormone ; blood ; Male ; Testosterone ; blood ; Young Adult

OBJECTIVETo explore the roles of basic fibroblast growth factor (bFGF) on tube formation induced by xuefu zhuyu decoction (XZD) under non-anoxia condition.

METHODSUsing serum pharmacology technique, endothelial cell line ECV304 cells were incubated in routine 95% O2. ECV304 cells were intervened by 1.25%, 2.50%, and 5.00% XZD containing serums and the vehicle serum for 48 h. The effects of XZD on tube formation, bFGF contents and its transcription levels were assessed by in vitro tube formation assay, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR), respectively.

RESULTSThree concentrations of XZD containing serums could not only obviously promote the tube formation bFGF level, but also up-regulate bFGF contents in the supernate and its transcription levels. The shapes of lumens were more regular in those induced by 1.25% and 2.50% XZD containing serums.

CONCLUSIONXZD induced angiogenesis via up-regulating the bFGF expression under non-anoxia condition.

Animals ; Cell Line ; Drugs, Chinese Herbal ; pharmacology ; Endothelial Cells ; drug effects ; metabolism ; Female ; Fibroblast Growth Factor 2 ; metabolism ; Humans ; Male ; Neovascularization, Physiologic ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the possible mechanisms of miR-21-mediated regulation of proliferation and activation of hepatic oval cells.

METHODSThe 2-acetamidofluorene/partial hepatectomy (2-AAF/PH) method was applied to generate hepatic oval cell activation model in male Sprague-Dawley rats; after the 7 days of 2-AAF/PH or PH alone (control), the rats were sacrificed at 0 h, 6 h, 12 h, 24 h, 72 h and 168 h. Expression of miR-21 was detected by real-time PCR and differences between groups were evaluated using the two-sample t-test. Differential transcription of miR-21 target genes was assessed bioinformatically, and with western blotting to detect changes in protein expression of the target gene.

RESULTSThe rat hepatic oval cell activation model was successfully established.The 2-AAF/PH rats showed miR-21 expression beginning to increase at 12 h, peaking at 24 h, and decreasing thereafter until an increase at 168 h.For the control group, the miR-21 expression began to increase at 6 h, until 24 h when expression began steadily declining to reach the original level.Compared to the control group, the experimental group showed expression of miR-21 that was significantly less at 6 h (P=0.039, t =3.029) and significantly more at 24 h and 168 h (P=0.026, t =-3.433 and P=0.007, t =-5.105). Among the predicted target genes of miR-21 were WW domain containing E3 ubiquitin protein ligase 1 (WWD), Smad family member 7 (Smad7), and polybromo-1 (Pbrm1).Smad7 protein expression began to decrease at 6 h in the control group, until reaching its minimum at 24 h when it increased; in the experimental group, SMAD7 expression increased at 6 h, then began to decrease with the minimum detected at 168 hour.In the control group, the Smad7 mRNA expression decreased slightly at 6 h, then began to increase, reaching its peak at 24 h when the expression fell to the original level. In the experimental group, the Smad7 mRNA expression began to increase at 6 h and reached its peak at 24 h when it decreased; the expression was little more than its original level at 168 h.Smad7 protein expression was negatively correlated with miR-21, and Smad7 mRNA expression was positively correlated with miR-21 but negatively correlated with Smad7 protein expression.

CONCLUSIONmiR-21 may play a vital role in the activation and proliferation of hepatic oval cells.As a target gene of miR-21, Smad7 might be involved in the process.

2-Acetylaminofluorene ; Animals ; Cell Proliferation ; Hepatectomy ; Hepatocytes ; cytology ; Liver ; cytology ; Male ; MicroRNAs ; genetics ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction

Objective To observe the influence of targeted gene VEGF silencing of bladder cancer cell line T 24 on differentiation, maturation and function of dendritic cells .Methods A lentiviral vector named LV-VEGFA-RNAi ( experimental group ) for gene silencing targeting VEGF and a lentiviral vector named LV-CON ( negative control group ) without any valid sequences were constructed .The blank control group accepted no intervention measures . The expression of VEGF's mRNA and protein of T24 cells from each group were detected by RT-PCR and ELISA respectively .Then the immature DCs were co-cultured respectively with the supernatant of all the groups as men-tioned above.CD1a, CD83 as the maturation marker and CD86 as the immunity marker of the DCs were detected by flow cytometry.Results The expression of VEGF's mRNA and protein of T24 cells in the experimental group were obviously inhibited ( P<0.05 ) as compared with that in the negative control group and the blank control group.DCs of the experimental group had an obviously increased ( P<0.05 ) expression of CD1a, CD83 and CD86 compared with the negative control group and the blank control group .Conclusions Targeted gene VEGF silencing by RNAi has advantages to the growth and immunity of DCs , which may strengthen the anti-tumor ca-pacity of the DCs by repairing their damaged immune monitoring function .

Cognitive dysfunction is the impairment of higher brain functions.Cognitive impairment caused by neuropsychiatric diseases has caused serious impact on patients'quality of life and the outcome of the disease.The transcranial alternating current stimulation(tACS)improves cognitive function by modulating neural oscillations of specific frequencies,affecting the release of neurotransmitters such as serotonin and dopamine,and enhancing local and distal synchronization of brain networks.Specific frequencies of tACS can improve the cognitive impairment caused by Alzheimer disease(AD),schizophrenia,and depression,among which the gamma and theta frequencies of tACS have the most significant effects on cognitive function.tACS has high safety and low operational difficulty,and has great potential to improve cognitive function.

ABSTRACT:OBJECTIVE To observe the effects of iridoid glycoside extract from Corni Fructus(ECO)on glucose consump-tion and isoproterenol (ISO)-induced lipolysis in 3T3-L1 mature adipocytes and possible mechanism.METHODS Glucose consumption of mature adipocytes intervened by ECO for 24 h was detected in GOP-POD method.After 2 d of ECO interven-tion,colorimetric method was used to evaluate the release amount of glycerol from 30 min ISO-induced lipolysis.The expres-sion of AMPK,GLUT4 and HSL mRNA were detected by Real-time PCR and phosphorylation levels of AMPK and ACC were evaluated by immunoblot.RESULTS In mature 3T3-L1 adipocytes,1 g/L ECO intervention increased glucose consumption and reduced the glycerol release amout from lipolysis induced by ISO with different concentrations.0.2 g/L and 0.04 g/L ECO decreased 100 nmol/L ISO-induced lipolysis.After 2 d intervention,ECO upregulated the levels of AMPK and GLUT4 mRNA and decreased the gene expression of HSL.1 g/L ECO promoted the phosphorylation of AMPK and ACC.CONCLUSION ECO can increase glucose consumption and inhibited ISO-induced lipolysis in 3T3-L1 mature adipocytes and the effects might be related to AMPK regulation.

Objective To explore the knowledge,attitude and practice about insulin injection among patients with diabetes and identify the factors that influencing patients' practice,so as to provide foundation for making effective interventions.Methods Totals of 100 patients with diabetes who needs insulin injection by self or families were conveniently selected to complete a self-designed questionnaire on the knowledge,attitude and practice about insulin injection.Results The knowledge score and practice score were (66.25 ± 9.84) and (43.67 ± 18.78),respectively.Analysis showed that "unnecessary" and "waste" were two main reasons influencing patients' practice.Patients' knowledge about insulin injection was related to patients' practice.Patients with complications or those in endocrinology wards had better knowledge.Patients who have complications or retired or were injected by families were more comply with standard injection,compared to those who do not.Conclusions The knowledge about insulin injection was insufficient among patients with diabetes who needs self injections,and so the practice was not optimistic.New education model should be introduced to help patients better understand the importance of standard practice procedure and actively undertake self-management responsibility and change the misconduct.

OBJECTIVE: Clozapine is one of the most commonly used antipsychotic drugs in China. To date, few studies have investigated the patterns the prescription of clozapine nationwide. The present study examined these patterns in China in 2006 and identified the demographic and clinical characteristics associated with the use of clozapine. METHODS: Using a standardized protocol and data collection procedure, we surveyed 5,898 patients with schizophrenia in 10 provinces with differing levels of economic development. RESULTS: Overall, clozapine had been prescribed for 31.9% (n=1,883) of the patients; however we found considerable variation among the 10 provinces. The frequency of clozapine use was highest in Sichuan (39.3%) and lowest in Beijing (17.3%). The mean daily dose of clozapine was 210.36+/-128.72 mg/day, and 25.1% of the patients were treated with clozapine in combination with other antipsychotics. Compared with the group not receiving clozapine, clozapine-user had been treated for longer durations and had experienced a greater number of relapses and hospitalizations. Furthermore, those in the clozapine-user had lower family incomes, were less able to seek psychiatric services, and more likely to be male and have a positive family history of schizophrenia. A multiple logistic regression analysis revealed that age, sex, professional help-seeking behaviors, duration of illness, economic status, educational level, and clinical manifestations were associated with the use of clozapine. CONCLUSION: Clozapine use is common in China. However, use of the antipsychotic varies among provinces, and demographic and clinical factors play important roles in the prescription of clozapine.
Antipsychotic Agents ; China ; Clozapine ; Data Collection ; Educational Status ; Hospitalization ; Humans ; Logistic Models ; Male ; Prescriptions ; Recurrence ; Sampling Studies ; Schizophrenia