Objective To investigate the mechanism of an inhibitor of NADPH oxidases,diphenylene iodonium (DPI),in preventing radiation-induced lung injury.Methods Totally 48 adult SD male rats were randomly classified into 4 groups:control group (C),radiation group (R),radiation plus DPI group (R + D) and DPI group (D).The radiation induced pulmonary injury model was preformed by using 6 MV X-rays to deliver 8 Gy per day for 5 consecutive days with 40 Gy in total to the thorax of each animal.Rats in R + D group were subcutaneously administered with 0.02％ DPI (1 mg/kg) at 1 h prior to radiation while rats in D group received the same dose of DPI without radiation.DPI was given from 3 d before radiation to 30 d after the first radiation.Rats in C and D groups received the same dose of saline.Animals were sacrificed at 1 month and 6 months after radiation,respectively.The lungs were removed and processed for HE and Masson staining,hydroxyproline content measurement,and TGF-β1 immunohistochemical detection.Results At 1 month post-radiation,rats in R group showed typical alveolitis,the level of hydroxyproline was (0.69 ± 0.05) μg/mg,and the positive area of TGF-β1 expression was (39.97 ± 0.90) ％,while the level of hydroxyproline in R + D group was (0.55 ± 0.03) μg/mg and the positive area of TGF-β1 expression was(33.83 ± 1.55) ％,rats in R + D group showed less severe alveolitis compared with R group(t =5.32,5.93,P ＜0.05).At 6 months post-radiation,rats in R group showed typical lung fibrosis with hydroxyproline level of (1.04 ±-0.02) μg/mg and TGF-β1 expression of (37.80 ± 0.85) ％,whereas the hydroxyproline level in R + D group was (0.85 ± 0.02) μg/ mg,the TGF-β1 expression was(23.93 ± 1.16)％,rats in R + D group showed moderate lung fibrosis(t =15.77,16.68,P ＜ 0.05),rats in C and D group had no noticeable changes.Conclusions Diphenylene iodonium could prevent radiation-induced lung injury by reducing the level of hydroxyproline and the expression of TGF-β1.

Endothelin(ET)is the most potent mammalian vasoconstrictor identified to data. As a pathogenic factor,ET is involved in the genesis of many diseases. In this study, a pair of primers was designed and synthesized according to the human ETB receptor gene (hETBR)sequence. A 394bp of DNA fragment was amplified by polymerase chain reaction(PCR) and labeled with a-32p-CTP using Random Primer-Labeling method. With this probe, rabbit lung cDNA library was screened by in situ hybridization and 11 positive clones were identified. Sequencing result showed that a complete reading frame of rabbit ETB receptor(rETBR)cDNA could be produced from three positive clones of eleven. By a series of subcloning,a recombinant plasmid including the 1326 bp of rETBR coding sequences, named pBlu Script-rETBR, was constructed. The deduced amino acid sequence indicated that the rETBR is 441 residues in length, with an expected molecular mass of approximately 49.44 kD. N-terminal 18 residues is the potential signal peptide (Score＝11.11)and therefore the molecular mass of mature rETBR is 47.65 kD with 423 amino acid residues. Analysis of the rETBR hydropathy profile indicates the presence of seven hydrophobic regions, putative transmembrane domains. Potential N-glycosylation sites are the 60th and the 118 th. The structure exhibits a significant sequence and topographical similarity with G protein-coupled receptors.

OBJECTIVETo identify factors associated with YMDD mutation in patients with chronic hepatitis B before and after lamivudine treatment in Zunyi region.

METHODS53 patients with chronic hepatitis B were enrolled in this study, HBV DNA,HBV markers, ALT, AST, TBil, albumin in the serum were examined at 0, 3, 6, 12, 18 and 24 months after lamivudine treatment. HBV genotype and YMDD mutation were determined by sequencing before lamivudine treatment. YMDD mutation was checked again if serum HBV DNA rebound to more than 1 x 10(4) copies/ml after the initial decrease.

RESULTSHBV genotype in Zunyi region is constitute of B, C and B+C genotype. YMDD mutation occurred in 18 cases after lamivudine treatment, the rate of YMDD mutation was 15.1%, and 34.0% after 1 year and 2 years treatment. There are four types of mutation: rtL180M/M204V, rtL180M/M204I, rtM204I, rtL180M. rtM204V mutation in C gene was always accompanied by rtL180M mutation (100%). The rate of rtL180M/M204V mutation in genotype C group was significantly higher than that in genotype B group (77.8% to 25.0%), the same was true for the rtL180M/ M204I mutation (22.2% to 12.5%). There was no point mutation in genotype C group. The point mutation of rtM204I and rtL180M appeared only in genotype B group. Gender, nation, family history of hepatitis B and HBeAg were not associated with YMDD mutation (P more than 0.05), while the mutation rate was associated with the disease course and severity of disease. YMDD mutation did not occur in patients with low HBV DNA level (less than 10(5) copies/ml).

CONCLUSIONYMDD mutation after lamivudine therapy is associated with HBV genotype and P gene mutation type, and prolonged treatment increases the the mutation rate. In order to reduce the incidence of YMDD mutation, patients with shorter disease course, lower HBV DNA level, more serious liver damage should be treated with lamivudine.

Adult ; Alanine Transaminase ; blood ; Antiviral Agents ; pharmacology ; therapeutic use ; Aspartate Aminotransferases ; blood ; China ; epidemiology ; DNA Mutational Analysis ; DNA Primers ; DNA, Viral ; blood ; genetics ; Drug Resistance, Viral ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; drug therapy ; virology ; Humans ; Lamivudine ; pharmacology ; therapeutic use ; Male ; Mutation ; Polymerase Chain Reaction

BACKGROUNDTo study the relationship between human heparanase expression and biological factors regarding invasion, metastasis and prognosis of human non-small cell lung cancer (NSCLC).

METHODSThe expression of heparanase was assessed in 122 paraffin-embedded specimens and 38 freshly-taken tissues by immunohistochemical staining and Western blot. The relationship between heparanase expression and the clinicopathological factors was analyzed by Chi square test, multivariate analysis and Kaplan-Meier method.

RESULTSIn the immunoreactive cells, staining was mainly located in cytoplasma and membrane. Human heparanase was highly expressed in lung cancer tissues (78.7%, 96/122) while negative in epithelia of normal lung tissues. The level of heparanase was remarkably higher in NSCLC than that in normal tissues ( P = 0.043 ). Expression of heparanase significantly correlated with TNM stage ( P =0.025), lymphatic metastasis ( P =0.002) and vascular invasion ( P =0.000 3). The patients with positive heparanase expression had a significantly shorter survival than those with negative heparanase expression ( P =0.000 6). In multivariate analysis, only p-TNM stage, lymphatic metastasis and vascular invasion could be considered as prognostic factors.

CONCLUSIONSHeparanase might play an important role in the development, invasion and metastasis of NSCLC. It is indicated that patients with positive heparanase expression would have a greater chance of metastasis and a poorer prognosis. However, heparanase expression is not an independent prognostic factor.

BACKGROUNDObstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC).

METHODSThirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH + NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnI) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.

RESULTS(1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P < 0.005). The MDA concentration of the NAC group was lower than that of the control group (P < 0.01). (2) The serum cTnI concentration of the CIH and NAC groups was significantly higher than that of the control group (P < 0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P < 0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.

CONCLUSIONThe oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.

Acetylcysteine ; pharmacology ; Animals ; Free Radical Scavengers ; pharmacology ; Heart ; drug effects ; Hypoxia ; physiopathology ; Malondialdehyde ; metabolism ; Mice ; Mice, Inbred ICR ; Myocardium ; metabolism ; pathology ; Oxidative Stress ; physiology ; Random Allocation ; Superoxide Dismutase ; metabolism

Objective To observe the clinical efficacy and safety of alendronate tablets combined with alfacalcidolon capsules in the treatment of perimenopausal women with osteoporosis.Methods A total of 56 perimenopausal women with osteoporosis were randomly divided into control group and treatment group with 28 cases per group.Control group was treated with alfacalcidolon capsule 0.25 μg qd oral.Treatment group was given alendronate sodium tablet 70 mg qd oral,on the basis of control group.The chnical efficacy,serum aquaporin 1 (AQP1),matrix metalloproteinase 2 (MMP-2),bone alkaline phosphatase (BALP),type Ⅰ collagen C end peptide (CTX-Ⅰ)and adverse drug reactions were compared between two groups.Results After treatment,the total effective rates in treatment and control groups were 92.86％ (26/28 cases) and 71.43％ (20/28 cases) with significant difference (P ＜0.05).After treatment,the main indexes in treatment and control groups were compared:AQP1 were (23.53 ± 3.02),(30.65 ± 4.31) μg · L-1;MMP-2 were (60.37 ± 8.35),(66.45 ± 8.47) μg · L-1;BALP were (20.04±2.57),(24.38 ±3.32) pg · L-1;CTX-Ⅰ were (0.75 ±0.06),(0.83 ±0.09)ng · L-1,the differences were statistically significant (P ＜ 0.05).The adverse drug reactions in treatment group were based on diarrhea and nausea,which in control group was based on diarrhea and nausea.The incidence of adverse drug reactions in two groups were 7.14％ without significant difference (P ＞ 0.05).Conclusion Alendronate tablets combined with alfacalcidolon capsules have a definitive clinical efficacy in the treatment of perimenopausal women with osteoporosis,which can significantly reduce the serum levels of AQP1,MMP-2,BALP and CTX-Ⅰ,without increasing the incidence of adverse drug reactions.

Objective To observe the value of SS-3DUNet model based on spatially separable convolutions for automatically segmenting anal fistula in enhanced MR T1WI.Methods Totally 2 405 pelvic axial enhanced MR T1WI of 29 patients with anal fistula were retrospectively analyzed,and 1 537 images from 19 cases were randomly selected as training set,424 images from 5 cases were as validation set,444 images from 5 cases were as test set.A SS-3DUNet model was constructed based on spatially separable convolutions to automatically segment anal fistula in enhanced MR T1WI,and inter-layer feature enhancement module was incorporated to improve the location of fistula features.The model was trained in training set and the best one was selected based on validation set.Taking the results of manual labeling by clinicians,the efficacy of SS-3DUNet model for automatically segmenting anal fistulas was observed based on test set.Results The time of SS-3DUNet automatically segmenting anal fistula in a single image in test set was 0.59-0.61 s,and the coincidence of the boundary of fistula segmented by the model and manual label was high.The average Dice similarity coefficient,sensitivity and accuracy of SS-3DUNet for automatically segmenting anal fistula in test set was 0.746,70.04%and 82.93%,respectively.Conclusion SS-3DUNet model based on spatially separable convolutions could effectively automatically segmenting anal fistula in enhanced T1WI.

OBJECTIVETo investigate the genetic diversity of main germplasm of Atractylodes macrocephala in China and the genetic differentiation of the germplasm of A. macrocephala.

METHODA molecular marker ISSR was used to analyze the genetic diversity of 7 populations of A. macrocephala and a population of A. lancea.

RESULTTwelve primers were used in the PCR amplification of 86 samples of A. macrocephala and 5 samples of A. lancea. Sixty-three bands with sizes ranged from 100 to 2500 bp were generated from 12 primers. Of all the 63 bands, 55 bands were polymorphic among 86 individuals of A. macrocephala, the percentage of polymorphic bands were 87.30% at the species level. The percentage of polymorphic bands (PPL) for a single population ranged from 58.73% to 71.43% (mean, 64.85%). Among the 7 populations, a population from Panan, GM exhibited highest variability (PPL =71.43%; HE = 0.2835; I = 0.4267). A dendrogram constructed by an unweighted pair group method of cluster analysis showed that populations from Panan constructed one branch and separated from other populations. In the AMOVA analysis, low level of genetic differentiation among populations was detected, 90.52% of the variability existed in population.

CONCLUSIONThe genetic diversity of cultivated A. macrocephala in China is high, which is good for the production of high quality herb medicine.

Atractylodes ; classification ; genetics ; Genetic Variation ; Phylogeny ; Plants, Medicinal ; genetics ; Polymorphism, Genetic

OBJECTIVETo investigate the influence of vitamin D receptor (VDR) gene polymorphisms on susceptibility to type 1 diabetes mellitus (T1DM) in the Chinese Han population.

METHODOne hundred and thirty-six Chinese Han people, including 54 T1DM patients and 82 unrelated healthy subjects as control were genotyped by polymerase chain reaction-restriction fragment length polymorphism for three restriction sites in the VDR gene, which were ApaI, TaqI, and BamI.

RESULTSThe frequency of B allele of BsmI site in VDR gene was significantly higher in T1DM patients than in healthy subjects (P = 0.033) while no difference was found between the two groups in the distribution of ApaI and TaqI polymorphisms.

CONCLUSIONThe BsmI polymorphism of VDR gene may be associated with the susceptibility to T1DM in the Chinese Han population of Beijing.

Adolescent ; Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Child ; China ; DNA Primers ; genetics ; Diabetes Mellitus, Type 1 ; genetics ; Female ; Gene Frequency ; Humans ; Male ; Polymorphism, Restriction Fragment Length ; Receptors, Calcitriol ; genetics

Objective To observe the effects of Jieduan Niwan Prescription on IL-6 and TNF-α in serum and hepatic tissue in acute-on-chronic liver failure rats (ACLF); To study the partial mechanism of the treatment for ACLF. Methods The ACLF rat model was established by using human serum albumin immuno-induced hepatic fibrosis followed with D-galactosamine and lipopolysaccharide joint acute attack. The SPF Wistar male rats were randomly divided into normal group, model group and Jieduan Niwan Prescription group, respectively. The Jieduan Niwan Prescription group was treated by Jieduan Niwan Prescription after the acute attack for 24 h, and the rats were sacrificed respectively at 5, 10 and 15 days after gavage administration. Transmission electron microscope was employed to observe the ultrastructural changes in liver cells and ELISA was used to detect the contents of IL-6 and TNF-α in serum and liver tissue, respectively. Results Compared with the normal group, the contents of serum and liver tissue IL-6 and TNF-α in model group increased at each time point. Compared with the model group, the contents of serum and liver tissue IL-6 and TNF-α decreased in Jieduan Niwan Prescription group, especially in 15 days. Under the transmission electron microscope, the changes of ultrastructure of liver tissue were observed. With the passage of time, the degree of hepatocyte injury in model group gradually increased, but decreased significantly in Jieduan Niwan Prescription group at each time point. Conclusion Jieduan Niwan Prescription can effectively reduce the levels of IL-6 and TNF-α in serum and liver tissue, reduce the degree of liver damage, and has a certain protective effect on the liver.