Niemann-Pick disease type C (NPC) is an autosomal recessive lysosomal lipid storage disease associated with impaired intracellular cholesterol trafficking. A wide spectrum of clinical phenotype has been described, with a possible onset at all ages of life from the neonatal period to adulthood, more often in childhood. Typically, hepatosplenomegaly, dystaxia, dysphagia, dysarthria and dementia are presented in NPC patients. Neurologic symptoms vary according to the onset age, but prolonged neonatal cholestasis, splenomegaly, cataplexy and vertical supranuclear gaze palsy are more specific signs to the diagnosis of the disease. Impaired cholesterol trafficking and unesterified cholesterol accumulation in the late endosomes and lysosomals, as a results of mutations in NPC1 or NPC2 genes, are initial for the disease, and defective cellular autophagy, defective lysosomal calcium homeostasis and oxidative stress may all play roles in the physiological processes. The definite diagnosis requires demonstration of unesterified cholesterol accumulated in fibroblasts cultured from skin biopsies or of pathogenic mutation of NPC1/NPC2 genes. Miglustat, the only available treatment approved to date, can alleviate neurological symptoms and slow disease progression when administered earlier.
Diagnosis, Differential ; Humans ; Niemann-Pick Disease, Type C ; diagnosis ; etiology ; genetics ; therapy

This study is to investigate the effect of total flavonoids of Uygur medicine bugloss (BTF) on rats with myocardial ischemia/reperfusion injury, and to explore the mechanisms by which it acts. Left anterior descending (LAD) coronary artery in rats was occluded for 30 min followed by 4 h reperfusion. Meanwhile, BTF dissolved in saline was administered intraperitoneally at dosage of 10, 30 and 50 mg x kg(-1). Electrocardiograph, infarction index, serum myocardial enzymes and heart function were determined to evaluate the effect of BTF. Some other observations were carried out to explore whether inhibiting inflammation and apoptosis is involved in the mechanisms underlying BTF. Our results showed that in ischemia/reperfusion injured rats BTF could dose-dependently reduce myocardial infarction index and myocardial enzyme leakage, and enhance heart function, indicating that it possesses significant cardio protection. ELISA analysis showed that BTF could decrease the content of myocardial inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. Western-blotting confirmed that BTF could increase the expression of anti-apoptotic protein Bcl-2 and reduce the expression of proapoptosis protein Bax. Further more, the phosphorylation level of PI3K and Akt was upregulated by BTF treatment. BTF can protect rat against myocardial ischemia/reperfusion injury. Anti-inflammation and inhibition of apoptosis through upregulating PI3K/Akt signal pathway may contribute to the protective effect of BTF.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins ; Boraginaceae ; chemistry ; Flavonoids ; pharmacology ; Heart ; Interleukin-6 ; Myocardial Infarction ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; Phosphatidylinositol 3-Kinases ; Phosphorylation ; Protective Agents ; Proto-Oncogene Proteins c-akt ; Rats ; Signal Transduction ; Tumor Necrosis Factor-alpha ; bcl-2-Associated X Protein

OBJECTIVETo evaluate the synergistic effects of tetrandrine (TET) on the antifungal activity of topical ketoconazole (KCZ) in the treatment of dermatophytoses.

METHODSThe minimum inhibitory concentrations (MICs) for KCZ and combined KCZ and TET were compared in vitro. A randomized, double-blind trial was conducted among 97 patients with dermatophytoses who were assigned to 3 groups and received: treatment with combination of 2% KZC and 2% TET cream (KCZ + TET group), or only 2% KZC cream (KCZ group), or 2% TET cream (TET group). Patients with tinea corporis and/or tinea cruris were treated for 2 weeks, separately. The patients with tinea pedis and/or tinea manuum were treated for 4 weeks.

RESULTSCompared with KZC alone, combined use of KZC and TET showed lower MICs against clinical isolates of dermatophytes (P<0.05 for all). In the patients with tinea corporis and/or tinea cruris, the rates of overall cure (clinical cure plus mycologic clearance) were 81.25% vs. 33.33% for combined treatment and KZC monotherapy, respectively, after 4 weeks. All clinical indices were significantly different between the combination therapy and only KCZ therapy groups (P<0.05). Among the patients with tinea pedis and/or tinea manuum after 4 weeks treatment, the overall cure rates in the KCZ + TET group and KCZ group were 75.00% vs. 40.00%, respectively. In the KCZ + TET group, all the clinical indices were significantly better than those in the KCZ group and TET group (P<0.05). The rates of overall efficacy in the TET group were all zero. No local skin redness or itching was observed during TET treatment. No clinically significant changes were found in post-treatment routine blood, urine, or stool tests, ECG, or tests for liver and kidney function; no serious adverse events occurred.

CONCLUSIONTET synergistically enhanced the clinical efficacy of topical KZC cream in the treatment of dermatophytoses.

Administration, Topical ; Adult ; Antifungal Agents ; administration & dosage ; adverse effects ; therapeutic use ; Benzylisoquinolines ; administration & dosage ; adverse effects ; therapeutic use ; Drug Synergism ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Ketoconazole ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Microbial Sensitivity Tests ; Tinea ; drug therapy ; Treatment Outcome

Objective To explore the methods of early etiological diagnosis and principles of endovascular embolization in Hunt-Hess Ⅳ—Ⅴ grade subarachnoid hemorrhage(SAH),and to evaluate the therapeutic efficacy.Methods Thirty-one patients underwent imaging examinations such as CT and DSA to make the early diagnosis of SAH.Meanwhile,Guglielmi detachable microcoil(GDC)was used to applying aneurysmal intracapsular embolization in the ruptured aneurysms,and efficient symptomatic treatment was adopted early postoperatively.The results were tested by ?~2 test.Results All 31 cases were diagnosed early and operated successfully.Among them,the aneurysm lumen was 100% occluded in 26 cases,95% occluded in 3 cases;90% occluded in 2 cases.There were 5 cases complicating with cerebral vasospasm.One case recurrent was cured with secondary complementary GDC embolization.Nine cases(29.0%)had permanent sequelae associated with SAH.According to the Glasgow prognosis score, the therapeutic efficacy was as following:6 patients were in grade Ⅰ,9 in grade Ⅱ,4 in grade m,2 in grade Ⅳ,and 10 in grade Ⅴ;10 patients died,and the morality rate was 32.3%.None of them exhibited re-bleeding with follow-up period of 3 to 68 months postoperatively.Morality rates were significantly different between the group with aneurysmal diameter of 11—25 mm and the group of 5—10 mm(?~2=6.60,P

Objective:To detect the expression of six miRNAs for miR-146a,miR-224,miR-34c,miR-200a,miR-148b,miR-375 level in primary hepatocellular carcinoma patients tissues and serum,and to explore the correlation between the expression of miRNA and inflammatory factors,in the hope of verification whether circulating miRNA could be used as an ideal blood borne biomarker for early detection of primary liver cancer.Methods:Venous blood samples were collected from patients with primary liver cancer,hepatitis,cirrhosis and healthy controls,cancer tissues and para cancerous tissues were collected from patients with cancer.After the total RNA was extracted,the relative expression levels of miRNA were detected by real-time quantitative PCR,and the relationship between the expression level of miRNA and the expression of serum tumor markers AFP,CEA,CA19-9 and CA125 was detected.The correlation between the expression level of miRNAs and the expression of HBsAg,anti-HBs,HBeAg,anti-HBe,anti-HBc and inflammatory factors IL-12,IL-4,IL-6,IL-10,IFN-γ,TNF-α was detected as well.Results:Compared with the healthy group,the expression of miR-34c,miR-224 and miR-146a in serum and tissues of PHC group was significantly up-regulated,and the expression of miR-200a,miR-148b and miR-375 in serum and tissues of PHC group was significantly down regulated.The difference was statistically significant.There was a regression relationship between HBsAg and serum miR-375 and miR-146a,and miR-375 decreased with the increase of HBsAg expression,while miR-146a increased with the increase of HBsAg.There was a regression relationship between IFN-γ and miR-146a,miR-146a increased with the decrease of IFN-γ expression.The diagnostic ability of miR-375 and miR-146a was greater than that of CA19-9 and AFP.Conclusion:MiR-146a,miR-224,miR-34c,miR-200a,miR-148b,miR-375 in serum and tissue of primary hepatocellular carcinoma are differentially express,among them,the diagnostic ability of miR-375 and miR-146a is better than that of AFP and CA19-9,and serum miR-375 and miR-146a may be the new markers for early diagnosis of PHC.

This study was aimed to prepare a reconstructed B. Fragilis-derived recombinant α-galactosidase developed for human B to O blood group conversion. Based on the construction of recombinant E. Coli (DE3) which can express α-galactosidase, the inducing time and inducer concentration were optimized for high expression of α-galactosidase. Then, the expression products in supernatant were purified by cation and anion exchange column chromatography. The purified α-galactosidase was used to treat B group red blood cells in phosphate buffer (pH 6.8) for 2 hours to prepare O group red blood cells. The results showed that the optimal inducing conditions for α-galactosidase expression were IPTG 0.1 mmol/L, 37°C and 2 hours. The specific enzyme activity of purified protein increased from 0.42 U/mg to 2.1 U/mg as compared with pre-purification. And, the conditions of B to O blood group conversion were 26°C, pH 6.8 (neutral pH condition) and 2 hours. Moreover, 225 µg of the enzyme could converse 1 ml B red blood cells to O completely. It is concluded that the technology of expression and purification of recombinant α-galactosidase has been established, and the purified protein can converse B red blood cells to O completely, which means that an effective enzyme conversing B red blood cells to O has been obtained.
ABO Blood-Group System ; immunology ; Bacteroides fragilis ; enzymology ; Cloning, Molecular ; Escherichia coli ; metabolism ; Humans ; Recombinant Proteins ; biosynthesis ; alpha-Galactosidase ; biosynthesis

OBJECTIVETo observe the effects of Yixin Kangtai Capsule (YKC) on sperm concentration and motility, superoxide dismutase (SOD) and malondialdehyde (MDA) in aged SD rats, and to explore its possible mechanisms of action.

METHODSWe randomly assigned fifty 24-month-old male SD rats to five groups of equal number: blank control, testosterone undecanoate, high-dose YKC, medium-dose YKC and low-dose YKC, and treated them intragastrically with physiological saline at 10 ml/kg, testosterone un-decanoate suspension at 4 mg/kg, and YKC at 0.6 g/kg, 0.3 g/kg and 0.15 g/kg, respectively, once a day for 30 days. Then we harvested the epididymides, which were stripped of fat and envelope, cut into pieces and placed in the saline at 37 degrees C for 10 to 15 minutes. Then we detected the sperm parameters with the Weili CASA sperm analysis system, measured the levels of serum SOD and MDA, and, following HE staining, observed the histomorphological changes of the testicular tissue under the light microscope.

RESULTSCompared with the controls, the rats treated with high-, medium- and low-dose YKC exhibited significantly increased sperm concentration ([152.3 +/- 24.0] x 10(6)/ml vs [334.5 +/- 97.7], [302.7 +/- 158.9] and [221.4 +/- 75.6] x 10(6)/ml, P < 0.05) and markedly improved sperm motility ([26.5 +/- 2.0]% vs [35.5 +/- 5.9], [33.1 +/- 5.4] and [28.4 +/- 2.1]%, P < 0.01). High-dose YKC significantly increased the level of serum SOD ([22.0 +/- 5.3] U/ml, P < 0.01) and reduced the content of MDA ([13.6 +/- 4.6] nmol/ ml, P < 0.01). Testicular histology showed that YKC induced more active proliferation of cells, and increased the number of dividing cells and that of mature sperm in the lumen, with little interstitium, abundant blood vessels, and well-developed stromal cells.

CONCLUSIONYixin Kangtai Capsule can improve spermatogenesis in aged SD rats by regulating the levels of SOD and MDA.

Aging ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Sperm Motility ; drug effects ; Spermatogenesis ; drug effects ; Superoxide Dismutase ; blood

αGal, a xenotransplantations antigen (XTA), can lead to hyper acute reaction (HAR) in xenotransplantation. α-Galactosidase from B. fragilis is a novel galactosidase belong to CAZy GH110 which can clear the terminal αGal from branched and linear oligosaccharides. This study was purposed to investigate the removal effect of a novel α-galactosidase on α-Gal XTA on surface of red blood cells. The αGal XTA from the red blood cells of cattle, pig, dog and rabbit was digested by using recombinant α-galactosidase; the α-Gal antigens on surface of cells was detected by flow cytometry. The results showed that the XTA was disappeared completely or mainly. It is concluded that the novel α-galactosidase is a potential enzyme to remove the XTA on the surface of xenotransplants and can be used to overcome the HAR in xenotransplantation.
Animals ; Antigens, Heterophile ; immunology ; Cattle ; Dogs ; Epitopes ; Erythrocytes ; immunology ; Macaca mulatta ; Mice ; Mice, Inbred BALB C ; Rabbits ; Swine ; Transplantation, Heterologous ; alpha-Galactosidase ; immunology

OBJECTIVETo search for an effective therapy for functional anejaculation (AE).

METHODSFifty-five AE patients were randomized into a treatment group (n = 30) and a control group (n = 25), the former treated with Yangjing Capsule (once 5 pills, tid) and low-dose tadalafil (5 mg, qd alt, 1 h before bedtime), while the latter with oral ephedrine (25 mg before bedtime). Meanwhile, the patients were advised to expose themselves to sexual stimulation, reduce the frequency of sexual intercourses and quit masturbation. The medication lasted 1-3 months, followed by observation of the therapeutic effects.

RESULTSThe total effectiveness rate was 83.34% in the treatment group, 11 cases cured, 8 obviously improved, 6 improved and 5 unimproved, significantly higher than 40.00% in the control group, 4 cases cured, 3 obviously improved, 3 improved and 15 unimproved (P < 0.05).

CONCLUSIONYangiing Capsule plus low-dose tadalafil is safe and effective for the treatment of functional anejaculation.

Adult ; Capsules ; Carbolines ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Infertility, Male ; drug therapy ; Male ; Phytotherapy ; Sexual Dysfunction, Physiological ; drug therapy ; Tadalafil ; Treatment Outcome ; Young Adult

To screen potential hamster chymase 2 inhibitors, a high-throughput screening (HTS) model was established. Recombinant hamster chymase 2 with active form was cloned and expressed in E. coli. The HTS model with total volume of 50 microL in 384-well microplate was based on fluorescence analysis and was proved sensitive as well as specific (Z' = 0.84). A total of 40 080 samples (including 28 060 compounds and 12 020 natural products) were screened, and 613 samples with inhibition greater than 90% were selected for further rescreening. Finally, compounds J16647 and J16648 were identified with high inhibitory activity on chymase 2, and whose IC50 values were 0.823 and 0.690 micromol x L(-1), respectively.
Animals ; Chymases ; analysis ; antagonists & inhibitors ; Cricetinae ; Enzyme Inhibitors ; analysis ; pharmacology ; Escherichia coli ; metabolism ; High-Throughput Screening Assays ; methods ; Inhibitory Concentration 50 ; Rats ; Structure-Activity Relationship