Objective To investigate the prevalence and spectrum of β-thalassemia mutations in C, uangdong province, and provide a reference for prenatal diagnosis and genetic counseling in this population. Methods Three thousand two hundred and forty-seven blood samples were randomly selected from Guangzhou and 2984 blood samples from Shenzhen from January in 2005 to January in 2009. PCR and reverse dot blot hybridization (RDB) were adopted for detection of β-thalassemia mutations in Guangzhou and Shenzhen city. Results Seven hundred and fifty-one individuals in Guangzhou were found to have β-hemoglobin gene mutations, the detection rate was 23.13%(751/3247); 10 different mutations were identified, namely CD41-42(-TCTT), IVS-Ⅱ-654(C→T), -28(A→G), CDI7(A→T), CD71-72(+A), 13E, IVS-I-1(G→T), CD43(G→T), -29(A→G), CDI4-15(+G), which accounted for 42.53% (336/790) ,25.19% (199/790), 12.66% (100/790), 10.89% (86/790) ,3.29% (26/790), 2.15%(17/790), 1.27%( 10/790), 1.14%(9/790) ,0.51%(4/790) ,0.38%(3/790), respectively; the most common mutation was CD41-42(-TCTT), which accounted for 42.53%(336/790). In Shenzhen, 179 individuals were found to have β-thalassemia mutations, the detection rate was 6.00% (179/2984); 8 different mutations were identified excluding CD43 (G→T) and CD14-15 (+G); the most common mutation, however, was IVS-lI--654(C→T), which accounted for 40.44% (74/183). Conclusions The β-thalassemia mutations in Guangdong province are not only frequent, but also obviously heterogeneous, and the mutations differ from region to region. CD41-42 (-TCTT),ⅣS-Ⅱ-654(C→T), -28(A→G), CD17(A→T) were the 4 predominant mutations.

Objective To explore the effect of intravenous immunoglobulin (IVIG) on immunity and outcome for sepsis in children.Methods Eighty-four children who met the diagnosis of sepsis were included in study and divided into treatment group (36 cases) and control group (48 cases ).The patients in teatment group were administered IVIG with the dose of 1 g/kg.Peripheral venous blood samples of patients in both groups were collected before (0 h),24 h,72 h and 5 d after administration to detect the numbers of immunocyte including CD3 +,CD4 +,CD56 +,CD19 +,CD8 +cells by flow cytometry and the levels of cytokines including tumor necrosis factor (TNF)-at,interleukin (IL)-10,IL-1 7 by enzyme linked immunosorbent assay.The numbers of immunocyte and levels of cytokines and TNF-a/IL-10 were compared and the mortality at 28 days was assessed between two groups.Results The numbers of CD3 +,CD4 +,CD56 +,CD19 +cells and the levels of TNF-a,IL-17 and TNF-α/IL-10 of patients in teatment group were significantly decreased than those in control group at 24 h,72 h and 5 d afte administration ( P ＜0.05 ) and showed downtrend.However,the level of IL-10 increased significantly (P ＜ 0.05 ) and showed uptrend in treatment group.The number of CD8+ cells had no change.No difference of mortality was observed between two groups (27.7％,10/36 vs 16.6％,8/48,x2 =1.50,P =0.169,OR =1.92,95％ CI:0.671 ～5.510).Conclusion IVIG can suppress the immunity of children with sepsis and has no survival benefit.

Objective To study the relationships of hemoglobin(Hb)level with the levels of neurohormones,and cytokines,and the effect of them on ventricular remodeling in patients with congestive heart failure(CHF). Methods Hb level,serum angiotensinⅡ(Ang Ⅱ ),tumor necrosis factor-α(TNF-α),nitric oxide(NO),soluble intereellular adhesion molecule-1(sICAM-1)and B-type natriuretic peptide(BNP)were measured in 121 CHF patients.The left ventrieular ejection fraction (LVEF)from echocardiography,left ventricular mass index(LVMI),and mean wall stress(MWS)were calculated. Results The levels of Ang Ⅱ,TNF-α,NO,siCAM-1,BNP[(144.5±64.1)ng/L,(92.3±6.4)ng/L,(65.2±4.2)μmol/L,(253.6±26.0)μg/L,(1294.0±223.0)ng/L]and LVMI,MWS in the anemia group of CHF patients were higher than those in the non-anemia group[(76.7±48.5)ng/L,(55.6±10.2)ng/L,(42.1±11.9)μmol/L,(237.18±33.26)μg/L,(437.0±115.0)ng/L,all P＜0.01].With the increase of anemia severity,the levels of AngⅡ,TNF-α,NO,siCAM-1,BNP and LVMI,MWS were significantly increased.There were negative correlations between Hb level and the 1evels of AngⅡ,TNF-α,NO,siCAM-1,BNP,LVMI,MWS(r=-0.8173,-0.8509,-0.6001,-0.6692,-0.6283,-0.8604,-0.8733,all P＜0.01),and negative correlations between LVMI,MWS and Hb levels and LVEF(P＜0.01). Conclusions Neurohormones and cytokines play roles in ventrieular remodeling and anemia in CHF aggravates the severity of ventricular remodeling.

Objective To investigate the effects of edaravone (EDA) on cell apoptosis induced by endoplasmic reticu?lum stress (ESR) after spinal cord injury (SCI) in rats. Methods Thirty-six healthy adult SD rats were randomly divided in?to three groups (12 rats for each group):Sham group, SCI group and EDA group. The rat model of SCI was made by Allen’s method and the sham group was only received laminectomy and kept the spinal cord intact. Rats in sham group and SCI group accepted the same volume and frequency of saline injection as EDA group. The EDA group was given 10 mg/kg EDA once every 12 h intraperitoneally. Three days after injuring, the spinal cords were harvested, and the protein levels of C/EBP homologous protein (CHOP), Cleaved caspase-12 and Cleaved caspase-3 were detected by Western blot assay. Immunofluo?rescence staining was used to analyze the positive ratio of caspase-12 and CHOP in spinal cord of three groups. Meanwhile, TUNEL staining was used to identify cell apoptosis of spinal cord. Results Compared with sham group, the protein levels of CHOP, Cleaved caspase-12 and Cleaved caspase-3 were obviously higher in SCI group (P<0.01);the proportion of Cas?pase-12 and CHOP positive cells was significantly increased (P<0.01), and the apoptotic rates were also significantly in?creased in spinal cord (P<0.01). However, compared with SCI group, the protein levels of CHOP , Cleaved caspase-12 and Cleaved caspase-3 were significantly decreased in EDA group (P<0.01);the proportion of Caspase-12 and CHOP positive cells was significantly reduced (P<0.01), and the apoptotic rates were also significantly decreased in spinal cord (P<0.01). Conclusion EDA has neuroprotective potential to spinal cord injury. The mechanism of its neuroprotective effect may asso?ciate with its inhibitory effect to the cell apoptosis induced by endoplasmic reticulum stress after SCI.

Objective To study the effect of Exendin-4 on oxidative stress and neural apoptosis following spinal cord injury (SCI). Methods Adult male SD rats, with weight between 200-250 g, were randomly divided into three groups (12 in each group):Sham group, SCI group and Exendin-4 group (Ex-4 group). Rats in Sham group achieved spinal cord exposure. SCI group and Ex-4 group were induced according to Allen′s test (using a weight-drop device). Rats in Ex-4 group were ad?ministrated with Exendin-4 (10 μg/rat) through intraperitoneal injection immediately after establishment of SCI models. Rats in Sham group and SCI group were given the same volume of normal saline solution instead. Level of malondialdehyde (MDA) and the activity of catalase (CAT) were assessed in spinal cord tissues 24 hour after drug administrations. Neural apoptosis was detected by TUNEL staining and the expression levels of caspase-9 and AIF were determined using Western blot. Results Compared with Sham group, the levels of MDA, caspase-9 and AIF as well as neuronal apoptosis rate in?creased obviously, while activity of CAT decreased markedly in SCI group(P<0.01). Compared with SCI group, the levels of MDA, caspase-9 and AIF as well as the neuronal apoptosis rate decreased obviously, while activity of CAT increased re?markably in Exendin-4 group(P < 0.01). Conclusion Exendin-4 restrain neural apoptosis following spinal cord injury through relieving oxidative damage.

Objective To analyse the secondary structure of glutathions S-transferase of Echinoccocus granulosus(EgGST)and predict the B cell and T cell epitopes with informatics tools,in order to provide basic data and references for the following design of epitope vaccine.Methods The B cell and T cell epitopes of EgGST were predicted by DNAstar,Biosun software and Propred MHC class-Ⅱ Binding Peptide Prediction Server software.Results Many distinct antigenic epitopes of EgGST were identified by comput-er,there existed 8 B cell epitopes and 7 T cell epitopes.Conclusion Analysis of predicted epitopes of EgGST antigenic might be sig-nificant for future research of epitope vaccine.

Objective:To investigate the value of serum IL-23 in predicting the progression of prostate cancer at different stages of treatment.Methods:A total of 124 patients with metastatic prostate cancer diagnosed in Beijing Hospital from June 2018 to March 2019 were collected.Patients were TNM-staged according to the Prostate Cancer Guidelines of the European Association of Urology.Serum IL-23 levels were measured in patients with metastatic castration resistance prostate cancer(mCRPC), metastatic castration sensitive prostate cancer(mCSPC)and benign prostatic hyperplasia(BPH), respectively.Patients with mCRPC were subgrouped based on disease stability, and serum IL-23 levels were compared between the subgroups.Serum IL-23 levels in the groups were analyzed and compared with the Gleason score and the prostate-specific antigen(PSA)level.Results:The median value of serum IL-23 in the mCRPC group was 79.73(45.61, 95.63)μg/L, which was higher than that in the BPH group[30.88(15.01, 44.94)μg/L, Z=22.66, P=0.000]and the mCSPC group[46.10(35.27, 80.92)μg/L, Z=11.46, P=0.001]. Serum IL-23 levels were higher in the mCSPC group than in the BPH group( Z=7.17, P=0.007). Analysis for the subgroups showed that the median value of serum IL-23 was 110.25(88.47, 159.09)μg/L in mCRPC patients with unstable disease, which was higher than that in mCRPC patients with stable disease[46.52(44.97, 80.33)μg/L, Z=33.99, P=0.000]. There was no significant difference in serum IL-23 levels between mCRPC patients with stable disease and mCSPC patients[46.10(35.27, 80.92)μg/L]( Z=0.35, P=0.554). Conclusions:Serum IL-23 can be used as a potential biological indicator to predict the therapeutic effect of mCSPC and to predict tumor metastasis.

As the lymphocytes of immuno-mediated aplastic anemia (IMAA) are in active state, and the hematopoietic stem cells are in silence, this study was aimed to design a new strategy to treat IMAA. To utilize the difference of radiosensitivity between active lymphocytes and silent hematopoietic stem cells, the animals suffered from IMAA were treated with a single low dose of irradiation, killing the active lymphocytes to release its suppression to hematopoietic stem cells without injuring the hematopoietic stem cells. Therefore, the hematopoiesis can be restored. Experiments were completed in IMAA mouse model. At day 4 after making IMAA, the model mice were giren total body irradiation of 150 cGy, the non-treated model mice and normal mice irradiated with 150 cGy were used as control. The survive time and survive rate of mice, blood picture, the account of nucleated cell of bone marrow, and pathological changes of bone marrow and lymphoid tissues of each group mice were observed. The results were as follows: (1) Survive rate of IMAA mice in non-treated group was 12.5%, the average survive time was 27.4 +/- 13.4 days. 100% of IMAA mice in irradiation-treated group survived over 60 days. The mice of irradiation control group all survived. (2) The account of WBC of IMAA mice in non-treated group dramatically decreased until to die, and in the irradiation-treated group it was gradually increased since the 10th day after treatment and close to normal level at the 28th day. (3) The RBC hematocrit of IMAA mice in non-treated group progressively decreased at day 14, and IMAA mice of irradiation-treated group gradually recovered closely to normal level after slightly fall at day 14, similar to the mice of irradiation control group. (4) The account of nucleated cells of bone marrow in non-treated IMAA mice dramatically decreased, and in the IMAA mice of the irradiation-treated group it was rapidly increased following transient fall, and restored to normal. (5) Pathological observations showed that the bone marrow and spleen of non-treated IMAA mice demonstrated typical aplastic anemia pattern, including bone marrow failure, marked splenatrophy, but the bone marrow and lymphoid tissues in the IMAA mice of irradiation-treated group were recovered to normal at day 28 after treatment. It is concluded that the low dose of irradiation displayed a significant therapeutic effect to IMAA mice, their hematopoisis could be completely restored to normal. The mechanism of therapeutic effect may contribute to low dose of irradiation killing the immunocompetent lymphocytes, therefore, suppressing hematopoiesis. The experiment results not only set up a new strategy for IMAA treatment, but also provided a clue to study the mechanism of IMAA.
Anemia, Aplastic ; etiology ; immunology ; radiotherapy ; Animals ; Dose-Response Relationship, Radiation ; Female ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred DBA

OBJECTIVETo perform a Meta-analysis on peginterferon with interferon in treatment of HIV patients coinfected with refractory genotype HCV.

METHODSA literature search of Medline was conducted to identify eligible randomized controlled trials. Meta analysis was conducted to evaluate peginterferon and interferon in treatment of coinfected HCV genotype 1 or 4 in HIV patients.

RESULTSix trials of 88 matched the selection criteria. Total 1,131 patients with coinfection of HCV genotype 1 or 4 and HIV were included. Sustain viral response was higher in patients treated with peginterferon plus ribavirin compared with that of interferon plus ribavirin (26 % compared with 8 %) or peginterferon alone (26 % compared with 13 %). Severe adverse effects and withdrawal rates were similar for patients treated with peginterferon and patients treated with interferon.

CONCLUSIONPeginterferon plus ribavirin in treatment of patients with coinfection of genotype 1 or 4 HCV and HIV can achieve higher sustain viral response and the likelihoods of serious adverse effects and withdrawal rates are similar to other therapies.

Adult ; Antiviral Agents ; administration & dosage ; Drug Therapy, Combination ; Female ; Genotype ; HIV Infections ; complications ; drug therapy ; immunology ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; complications ; drug therapy ; virology ; Humans ; Interferon-alpha ; administration & dosage ; Male ; Polyethylene Glycols ; administration & dosage ; Randomized Controlled Trials as Topic ; Recombinant Proteins ; Ribavirin ; administration & dosage

AIMTo prepare the breviscapine liposomes and study the pharmacokinetics of breviscapine liposomes in Beagle dogs.

METHODSThe cross-over design (two periods) was employed. Six Beagle dogs were administrated a single intravenous dosage of 28 mg of breviscapine liposomes and reference preparation, respectively, scutellarin in plasma of 6 dogs at different sampling time was determined by RP-HPLC. The pharmacokinetic parameters were calculated by 3P97 program and compared by statistic analysis.

RESULTSThe mean concentration-time curves of breviscapine liposomes and reference preparation were both fitted to two-compartment model with the main pharmacokinetic parameters as follows: T 1/2 alpha were (4.4 +/- 0.7) min and (1.8 +/- 1.3) min respectively; T 1/2 beta were (55 +/- 27) min and (28 +/- 23) min respectively; V(c) were (1 580 +/- 265) mL and (2 460 +/- 2 200) mL respectively; CL(s) were (88 +/- 10) mL x min(-1) and (324 +/- 69) mL x min(-1) respectively; and AUC(0-720) were (363 +/- 42) microg x min x mL(-1) and (102 +/- 19) microg x min x mL(-1) respectively. The T 1/2 alpha, CL(s) and AUC(0-720) of breviscapine liposomes all had significant difference from those of reference preparation, after the data were examined by a one-way analysis of variance (ANOVA).

CONCLUSIONCompared with the reference preparation, breviscapine liposomes had a much more higher concentration in plasma and contained characteristic of sustained-release, which ameliorated the pharmacokinetic properties of scutellarin.

Animals ; Apigenin ; blood ; Area Under Curve ; Brain ; metabolism ; Cross-Over Studies ; Delayed-Action Preparations ; Dogs ; Drug Compounding ; Drug Stability ; Erigeron ; chemistry ; Female ; Flavonoids ; administration & dosage ; isolation & purification ; pharmacokinetics ; Glucuronates ; blood ; Injections, Intravenous ; Liposomes ; Male ; Plants, Medicinal ; chemistry