Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC₅₀ and CC₅₀ of compound 3 against HBV were 4.5 μmol·L^-1 and 92.3 μmol·L^-1, respectively. This is the first report of the antiviral activity of compound 3.

Objective To analyze the clinical and genetic characteristics of 10 Chinese patients with 17? hydroxylase/17,20 lyase deficiency (17OHD). Methods Clinical features and laboratory data were collected from 7 kindreds with 17OHD. PCR products and subclone sequencing were performed to screen the mutation of CYP17A1 gene. Results All patients had typical clinical presentation of sexual infantilism, hypertension and hypokalemia. The laboratory examinations indicated decreased plasma cortisol, 17-hydroxy progesterone, estradiol and testosterone, and elevated blood adrenocorticotrophic hormone(ACTH), follcie-stimulating hormone(FSH) and luteinizing hormone(LH). CT scan showed bilateral adrenal hyperplasia. 5 CYP17A1 mutations were identified, 4 of which are novel types D487_F489del, the most frequent mutation, was identified in 4 families and 45% alleles. Conclusion Our study indicates that 17OHD should be considered in the diagnosis of patients with sexual infantilism. D487_F489del is the most frequent mutation in Chinese 17OHD patients.

Objective To study the effects of total extracts of Averrhoa carambola L.( Oxalidaceae ) roots ( TEACLR ) in hyperlipidemia rats. Methods Sixty SD rats ( male and female in half ) were subjected to induction of hyperlipidemia by high -fat diet for established hyperlipi-demia rat model and were divided into the following groups:blank group, model group, positive control group ( simvastatin 2.5 mg? kg-1? d -1 orally) , TEACLR high, middle and low doses groups.Hyperlipidemia rats were treated with TEACLR, at doses of 1200, 600 and 300 mg? kg-1? d-1 for 5 weeks by gavages, respectively.After 5-week of treatment with drugs, blood sample and liver were collected for determi-nation.Results In contrast to the model group, TEACLR could reduce the contents of cholesterol, triglyceride, low-density lipoprotein, alka-line phosphatase in rat serum and liver malondialdehyde reduced obvious-ly [ ( 2.48 ±0.43 ) , ( 0.86 ±0.44 ) , ( 0.86 ±0.43 ) mmol? L-1 and (165.55 ±71.71 ) U? L-1 , ( 1.38 ±0.42 ) nmol? prot-1 , respective-ly] .The level of high -density lipoprotein and glutathione elevated evidently [(1.67 ±0.32)mmol? L-1,(3.43 ±0.78)nmol? prot -1]. Liver coefficient was significantly lowered ( 2.92 ±0.03 ) .TEACLR middle dose group could reduce the contents of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) obviously[(38.91 ±10.47),(99.91 ±30.74) U? L-1 ].TEACLR high dose group could increase the contents of superoxide dismutase evidently(24.44 ±3.13) nmol? prot -1 .Comparison with blank group and positive control group, there was no significant difference in TEACLR middle dose group.Conclusion TEACLR is proven to be able to decrease the level of hyperlipidemia markedly, which might be used as an effective therapeutic agent for hyperlipidemia and fatty liver.

BACKGROUNDThe mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.

METHODSMale Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively.

RESULTSAfter SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05).

CONCLUSIONSPFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.

Animals ; Apoptosis ; drug effects ; Benzothiazoles ; pharmacology ; therapeutic use ; Blotting, Western ; Disease Models, Animal ; Endothelial Cells ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; physiopathology ; Toluene ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Suppressor Protein p53 ; physiology ; Vasospasm, Intracranial ; prevention & control

The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage-independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.
Adult ; Animals ; Asian Continental Ancestry Group ; Cell Line, Tumor ; Cell Transformation, Neoplastic ; Colony-Forming Units Assay ; DNA, Viral ; metabolism ; Female ; Herpesvirus 4, Human ; genetics ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; genetics ; metabolism ; pathology ; virology ; Neoplasm Transplantation ; RNA, Viral ; metabolism ; Viral Matrix Proteins ; metabolism ; Viral Proteins ; metabolism

OBJECTIVETo investigate the association of childhood hemophagocytic syndrome (HPS) with human parvovirus B19 (HPVB19) infection, and to analyze the clinical features of this disease.

METHODSELISA and quantitative real-time PCR were used to detect HPVB19-IgM, HPVB19-IgG and HPVB19-DNA in 65 children with HPS (HPS group) and 65 healthy children (control group). The HPS group was divided into HPVB19-infected (n=14) and non-infected (n=51) groups according to the detection results of HPVB19-DNA. The clinical data of two groups were compared.

RESULTSThe positive rate of HPVB19-IgM in the HPS group (26%, 17/65) was significantly higher than that in the control group (9%, 6/65) (P=0.011), and there was no significant difference in the positive rate of HPVB19-IgG between the HPS (38%, 25/65) and control groups (29%, 19/65) (P=0.266). The infection rate of HPVB19 in the HPS group (22%, 14/65) was significantly higher than that in the control group (3%, 2/65) (P=0.001). Compared with the non-infected group, the HPVB19-infected group had significantly lower platelet count and hemoglobin level on admission, significantly more severe liver function damage, a significantly earlier onset time, and a significantly longer course of disease (P<0.05).

CONCLUSIONSThe pathogenesis of HPS may be associated with HPVBl9 infection. HPVBl9-infected children with HPS have more acute onset, more severe clinical manifestations, and a longer disease duration.

Adolescent ; Antibodies, Viral ; analysis ; Child ; Child, Preschool ; DNA, Viral ; analysis ; Female ; Humans ; Infant ; Lymphohistiocytosis, Hemophagocytic ; etiology ; Male ; Parvoviridae Infections ; complications ; Parvovirus B19, Human

BACKGROUNDTumor intrinsic chemoradiotherapy resistance is the primary factor in concomitant chemoradiotherapy failure in advanced uterine cervical squamous cell carcinoma. This study aims to identify a set of genes and molecular pathways related to this condition.

METHODSForty patients with uterine cervical squamous cell carcinoma in International Federation of Gynecology and Obstetrics stage IIb or IIIb, treated with platinum-based concomitant chemoradiotherapy between May 2007 and December 2012, were enrolled in this trial. Patients included chemoradiotherapy resistant (n = 20) and sensitive (n = 20) groups. Total RNA was extracted from fresh tumor tissues obtained by biopsy before treatment and microarray analysis was performed to identify genes differentially expressed between the two groups.

RESULTSMicroarray analysis identified 108 genes differentially expressed between concomitant chemoradiotherapy resistant and sensitive patients. Functional pathway cluster analysis of these genes revealed that DNA damage repair, apoptosis, cell cycle, Map kinase signal transduction, anaerobic glycolysis and glutathione metabolism were the most relevant pathways. Platelet-derived growth factor receptor alpha (PDGFRA) and protein kinase A type 1A (PRKAR1A) were significantly upregulated in the chemoradiosensitive group, while lactate dehydrogenase A (LDHA), bcl2 antagonist/killer 1 (BAK1), bcl2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1), and cyclin-dependent kinase 7 (CDK7) were upregulated in the chemoradiotherapy resistant group.

CONCLUSIONWe have identified seven genes that are differentially expressed in concomitant chemoradiotherapy resistant and sensitive uterine cervical squamous cell carcinomas, which may represent primary predictors for this condition.

Aged ; Carcinoma, Squamous Cell ; drug therapy ; genetics ; radiotherapy ; Chemoradiotherapy ; Female ; Humans ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Reverse Transcriptase Polymerase Chain Reaction ; Uterine Cervical Neoplasms ; drug therapy ; genetics ; radiotherapy

OBJECTIVETo evaluate the changes in retinal functions using multifocal electroretinography (mfERG) following intravitreal injection of Lucentis for treatment of wet age-related macular degeneration.

METHODSThis prospective study was conducted in 14 patients (9 men and 5 women, 14 eyes) with wet age-related macular degeneration receiving treatment with intravitreal injections of ranibizumab (Lucentis) in our hospital between October, 2014 and January, 2016. All the patients received the treatment following a 1+PRN protocol and after the initial injection, the patients were followed up monthly for 6 months to decide if additional injections were needed. The corrected visual acuity and mfERG findings of the patients were assessed before and at l, 3 and 6 months after the initial injection.

RESULTSAt the last follow-up, the patients received injections for a mean of 2.86∓1.58 times. The best corrected visual acuity (BCVA) at 1 month after the initial treatment was not significantly different from that before treatment (P=0.07), but showed significant improvements at 3 and 6 months (P<0.05). In mfERG, the implicit time of the 6 rings showed no significant decrease after the treatment, but the amplitude density of P1 and N1 in rings 1 and 2 improved significantly at 1, 3, and 6 months after the initial injection (P<0.05).

CONCLUSIONMultifocal electroretinography can serve as a useful modality for evaluating visual function changes in patients receiving intravitreal injection of Lucentis for wet age-related macular degeneration.

OBJECTIVETo analyze possible difference in bronchial asthma between ethnic and geographic groups and explore its correlates among Uygur and Han adults in Turpan Prefecture, Xinjiang.

METHODSOne hundred and sixty-six clinically diagnosed asthmatic patients at Turpan Prefecture Hospital, Xinjiang, 86 of Uygur and 80 of Han ethnic, and 166 1:1 matched controls from ophthalmological outpatient department at the same hospital were recruited into the study. Interview with questionnaire was conducted and serum levels of eosinophilic cation protein (S-ECP), total IgE (T-IgE) and specific IgE (S-IgE) were measured for all of the participants to study related factors for asthma with univariate and multivariate conditional logistic regression analyses.

RESULTSBronchial infection (OR(U) = 5.111, 95%CI: 1.203 - 21.710; OR(H) = 2.498, 95%CI: 1.471 - 5.069), family history of asthma (OR(U) = 3.078, 95%CI: 1.812 - 5.188; OR(H) = 2.711, 95%CI: 1.010 - 6.176), personal allergy history (OR(U) = 2.083, 95%CI: 1.043 - 4.162; OR(H) = 3.998, 95%CI: 1.739 - 9.198), weather change (OR(U) = 2.218, 95%CI: 1.199 - 3.778; OR(H) = 1.733, 95%CI: 1.004 - 2.994) and positive S-IgE (OR(U) = 1.592, 95%CI: 1.018 - 2.491; OR(H) = 3.858, 95%CI: 2.246 - 8.507) correlated with asthma in patients of both Uygur and Han ethnic. Percentage of asthma attack induced by respiratory infection [59.30% (51/86)] and weather change [36.05% (31/86)] in Uygur patients was significantly higher than that in Han ethnic [42.50% (34/80) and 21.25% (17/80), respectively], but percentage of those with personal allergy history [48.75% (39/80)] and positive S-IgE [52.50% (42/80)] in Han ethnic was significantly higher than that in Uygur [32.56% (28/86) and 30.23% (26/86), respectively]. Levels of S-ECP and T-IgE in patients with moderate and severe asthma of both Uygur and Han ethnic [(S-ECP(U) = 7.95 +/- 3.98) microg/L, S-ECP(H) = (11.21 +/- 4.74) microg/L, T- IgE(U) = (72.23 +/- 45.92) kU/L, T-IgE(H) = (108.81 +/- 64.07) kU/L, respectively]were significantly higher than those in controls of the same ethnic [S- ECP(U) = (1.94 +/- 1.16) microg/L, S-ECP(H) = (2.07 +/- 1.63) microg/L, T-IgE(U) = (46.19 +/- 32.47) kU/L, T-IgE(H) = (50.97 +/- 38.51) kU/L; t values were 8.96, 10.52, 2.81, 4.97, P < 0.01], higher in Han ethnic than those in Uygur (t values were 3.01, 2.68, P < 0.01).

CONCLUSIONBronchial infection, family asthma history, personal allergy history, weather change and positive S-IgE all were important correlates of asthma in Turpan Prefecture, Xinjiang. Levels of S-ECP and T-IgE in patients with moderate and severe asthma increased during its attacks, higher in Han ethnic than those in Uygur. Genetic and environmental factors may be involved in occurrence and development of asthma.

Adult ; Asthma ; blood ; epidemiology ; ethnology ; Causality ; China ; epidemiology ; Climate ; Environmental Exposure ; Eosinophil Cationic Protein ; blood ; Female ; Humans ; Immunoglobulin E ; blood ; Logistic Models ; Male ; Pedigree ; Surveys and Questionnaires

OBJECTIVETo evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension.

METHODSEight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender.

RESULTSA total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent.

CONCLUSIONIn males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.

Antihypertensive Agents ; pharmacology ; Blood Pressure ; drug effects ; genetics ; Cytochrome P-450 CYP11B2 ; genetics ; Female ; Humans ; Hydrochlorothiazide ; pharmacology ; Hypertension ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; Renin-Angiotensin System ; drug effects ; genetics