The function of the central nervous system was significantly altered under high-altitude hypoxia, and these changes lead to central nervous system disease and affected the metabolism of drugs in vivo. The blood-brain barrier is essential for maintaining central nervous system stability and plays a key role in the regulation of drug metabolism, and barrier structure and dysfunction affect drug transport to the brain. Changes in the structure and function of the blood-brain barrier and the transport of drugs across the blood-brain barrier under high-altitude hypoxia are regulated by changes in brain microvascular endothelial cells, astrocytes and pericytes, and are regulated by drug metabolism factors such as drug transporters and drug metabolizing enzymes. This article reviews the effects of high-altitude hypoxia on the structure and function of the blood-brain barrier and the effects of changes in the blood-brain barrier on drug metabolism. We investigate the regulatory effects and underlying mechanisms of the blood-brain barrier and related pathways such as transcription factors, inflammatory factors and nuclear receptors on drug transport under high-altitude hypoxia.

The structure and diversity of the intestinal flora in rats exposed to high altitude hypoxia was investigated. Animal experiments strictly follow the regulations of Medical Laboratory Animal Ethics Committee of Qinghai University, School of Medicine. SD rats were randomly divided into a control group, a moderate altitude hypoxia group, and a high altitude hypoxia group. The pH value of the feces was measured and histopathological changes in the small intestine were determined by HE staining, and the intestinal flora were characterized by 16S rDNA high throughput sequencing technology on the 3rd, 7th, 15th, and 30th day of hypoxia exposure. Compared with the control group, the fecal pH value of rats in the moderate altitude hypoxia group and the high altitude hypoxia group was decreased significantly. The lamina propria and submucosa capillaries were slightly dilated and congested on the 3rd day in the moderate altitude hypoxia group. In the high altitude hypoxia group the submembrane capillaries were dilated and congested, the lamina propria of the mucosa showed mild edema, and the lymphatic vessels were dilated on the 7th day. The composition and diversity of intestinal flora in these rats changed significantly with prolonged exposure to the high altitude hypoxic environment. A total of 35 phyla, 87 classes, 205 orders, 337 families, 638 genera, and 256 species were annotated in the three groups of rats, including Firmicutes, Clostridia, Clostridiales, Ruminococcaceae, Akkermansia, and Lactobacillus_murinus. Compared with the control group, the intestinal flora of the hypoxic groups showed the most significant changes by the 15th day. There were 9 microbiota of gut microorganisms with relative abundance in the moderate altitude hypoxia group, of which Rikenellaceae_RC9_gut_group bacteria was the most common, there were 19 different microbiota of gut microorganisms with higher relative abundance in the high altitude hypoxia group, of which Ruminococcaceae bacteria was the most common. The results of this study indicate significant changes in the intestinal flora with high altitude hypoxia, and establish a foundation for further research on the initiation and development of diseases and drug metabolism in high altitude hypoxia.

OBJECTIVE: To study the value of serum gamma-glutamyl transpeptidase (GGT) combined with direct bilirubin (DB) in the diagnosis of biliary atresia. METHODS: A total of 667 infants with cholestasis who were hospitalized and treated from July 2010 to December 2018 were enrolled as subjects. According to the results of intraoperative cholangiography and follow-up, they were divided into biliary atresia group with 234 infants and cholestasis group with 433 infants. The two groups were compared in terms of age of onset, sex, and serum levels of total bilirubin (TB), DB, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), and GGT. A receiver operating characteristic (ROC) curve analysis was performed for indices with statistical significance, and the area under the ROC curve (AUC) and the optimal cut-off value for diagnosis were calculated. RESULTS: The biliary atresia group had a significantly younger age of onset than the cholestasis group (P<0.001). There were no significant differences in sex, ALT, and AST between the two groups (P>0.05), while the biliary atresia group had significantly higher serum levels of TB, DB, TBA, and GGT than the cholestasis group (P<0.05). GGT combined with DB had the highest AUC of 0.892 (95% confidence interval: 0.868-0.916) in the diagnosis of biliary atresia. At the optimal cut-off values of 324.0 U/L for GGT and 115.1 μmmol/L for DB, GGT combined with DB had a sensitivity of 79.8% and a specificity of 83.2% in the diagnosis of biliary atresia. CONCLUSIONS GGT combined with DB has high sensitivity and specificity in the diagnosis of biliary atresia and can be used as an effective indicator for diagnosis of biliary atresia in infants.
Alanine Transaminase ; Aspartate Aminotransferases ; Biliary Atresia ; diagnosis ; Bilirubin ; Humans ; Infant ; gamma-Glutamyltransferase ; blood

Objective To investigate the effect of hepatitis B virus X (HBx)protein on the apoptosis of placental trophoblastic cells and its potential mechanism.Methods A pcDNA3.1 expression vector of HBx gene was constructed and transfected into JEG-3 and HTR-8 human placental trophoblastic cell lines,respectively.After transfection for 48 h,RT-PCR and immunofluorescence analyses were made to detect HBx mRNA and protein expressions.Flow cytometry was used to detect the early apoptosis status of JEG-3 and HTR-8 cells.The expressions of PI3K and p-Akt were detected by immunofluorescence and Western blotting.Results After transfection for 48 h,RT-PCR and immunofluorescence analyses showed that HBx mRNA and protein expressions were detected in JEG-3 and HTR-8 cells.Flow cytometry revealed that early apoptosis of JEG-3 and HTR-8 cells was reduced by pcDNA-HBx transfection (P <0.05).Immunofluorescence and Western blotting showed that PI3K and p-Akt were significantly upregulated in HTR-8 cells (P < 0.05 ).Conclusion HBx gene can be transfected into JEG-3 and HTR-8 human placental trophoblastic cell lines,respectively.After the transfection,the early apoptosis of JEG-3 and HTR-8 cells is reduced.Its inhibition on apoptosis is related to the activation of the PI3K/Akt signaling path-way.

OBJECTIVETo identify the anti-inflammatory effects of artificial musk aqueous extract(AME)on lipopolysaccharide-stimulated cytokines secreted or released by RAW264.7 cells.

METHODSCytokines including interleukin(IL)-6,IL-10,and tumor necrosis factor Α were determined using cytokine enzyme-linked immunosorbent assay kits.

RESULTCompared with model group,the levels of major cytokines such as tumor necrosis factor Α,IL-6,and IL-10 significantly decreased in different AME groups in a dose-dependent manner.

CONCLUSIONIn lipopolysaccharide-stimulated RAW264.7 macrophages,AME can remarkably inhibit the release of inflammatory cytokines and thus exerts its anti-inflammatory effects.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Cell Line, Tumor ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Fatty Acids, Monounsaturated ; pharmacology ; Inflammation Mediators ; metabolism ; Interleukin-6 ; metabolism ; Lipopolysaccharides ; Macrophages ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues.

METHODSTwo groups (n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR.

RESULTSAfter 4 weeks, the hemoglobin (Hb) level and red blood cell (RBC) count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney.

CONCLUSIONFindings from our study provides new understandings about the relative expression, regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2, divalent metal transporter 1, ferritin, iron regulation proteins 1 and 2, hereditary hemochromatosis protein, hepcidin, ferroportin 1 and hephaestin in intestine, liver, spleen, kidney, heart, and lung of rat.

Animals ; Ferritins ; blood ; Gene Expression ; Hepcidins ; Iron ; Liver ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of heme oxygenase-1 (HO-1) expression on cell growth and apoptosis in imatinib resistant chronic myeloid leukemia (CML) cells (K562/A02-IM), and explore the relationship between HO-1 gene and CML.

METHODSThe expression of HO-1 in 20 drug-resistant CML patients was detected by RT-PCR. Different concentrations of hemin were used to induce HO-1 expression of K562/A02-IM, HO-1 expression at different time was detected by RT-PCR and Western blot analysis. Cell apoptosis was detected by Annexin V/PI staining, and MTT assay was used to detect viability of K562/A02-IM cells after induction or inhibition of HO-1 gene by hemin and zinc protoporphyrin (ZPP).

RESULTSRT-PCR showed that HO-1 was expressed in the bone marrow mononuclear cells (BMMNCs). When treated with hemin at different concentrations (0, 10, 20, 40 µmol/L) for 16 h, the expression of HO-1 in K562/A02-IM was increased in a dose-dependent manner, and peaked at 20 µmol/L of hemin for 16 h. The apoptosis rates were (17.61 ± 0.01)%, (12.13 ± 0.11)%, (7.94 ± 0.03)% and (4.62 ± 0.15)% at 0,10, 20 and 40 µmol/L of hemin respectively for 16 h and were (14.7 ± 0.05)%, (8.1 ± 0.07)% and (16.3 ± 0.13)% at 20 µmol/L of hemin treatment for 8,16, and 24 h respectively. Hemin induced apoptosis of K562/A02-IM cells in a dose-dependent manner. The expression of HO-1 was induced in K562/A02-IM cells in a dose-dependent manner, and the survival of K562/A02-IM cells was significantly increased as compared to that of control group. When HO-1 was inhibited by ZPP, the cells survival was sharply decreased compared to that of the control group (P < 0.05).

CONCLUSIONHO-1 was expressed in the BMMNCs. It is a kind of molecules whose expression can be induced and can promote the growth of drug-resistant cells. Inhibition of HO-1 expression probably be used for the treatment of drug-resistant CML.

Antineoplastic Agents ; pharmacology ; Benzamides ; Cell Cycle ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Heme Oxygenase-1 ; genetics ; Humans ; Imatinib Mesylate ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology

Objective To understand distribution of the endemic fluorosis areas and running status of water-improving defuoridation projects in Gausu province. Methods In 2006, Gansu province endemic fluorosis areas, the content of fluoride in drinking water was measured in villages where water was not improved, running status of delluoridation projects was investigated and the content of fluoride in drinking water were determined in villages where water was improved. Dental fluorosis and skeletal fluorosis prevalence were examined in children in identified high-fluorlde villages. The fluorine content in drinking water was determined by F-ion selective electrode, dental fluorosis of children was diagnosed using Dean method, and adults skeletal fluorosis was diagnosed according to "National Standard for Clinical Diagnosis of Endemic Skeletal Fhiorosis" (GB 16396-1996). Results Water samples were examined in 1997 villages of 26 countries, among which water fluoride content was higher than 1.0 mg/L in 598 villages, accounting for 29.94%(598/1997). All 1215 water-improving and defluoridation projects had been investigated, among which 94.90%(1153/1215) of the projects were functioning well, and intermittent and abandoned projects accounted for 2.96%(36/1215) and 2.14%(26/1215). Mean fluoride of treated water of 1084 water-improving and defluoridation projects had water fluoride content ≤ 1.0 mg/L, accounted for 90.79%(1084/1194) ; mean fluoride of water from 1068 water-improving and defluoridation projects had water fuoride content ≤ 1.0 mg/L, accounting for 91.75%(1068/1164). Total 86 390 children of 8 to 12 year-old were examined, the detectable rate of dental fluorosis was 22.47%(19 414/86 390) and 142 211 adults above 16 year-old were examined, the detectable rate of skeletal fluorosis was 4.20%(5967/142 211). Conclusions Some villages yet have water fluoride content exceeding the standard. Some projects are abandoned and running badly, leading to fluoride content exceeding the standard. In a few areas, the prevalence of children dental fluorosis and adult skeletal fluorosis still exists in Gansu province, the task of prevention and control for endemic fluorosis is still arduous. We must raise the effect of prevention and treatment of this disease.

Objective To investigate the effect of seafood intake on the urinary iodine level in women for exploring an alternative to iodine supplementation.Methods Healthy pregnant women and non-pregnant women, aged 20～40 years,were selected during their health examination in local women'S health care in 2006.The types of seafood and its intake frequency were recorded from these women.and urine and kitchen salt samples were collected for iodine determination.Results A total of 198 women including 148 pregnant and 50 non-pregnant women were recmitod for this study;they had a median level of urine iodine of 87.51 mg/L.The median levels of urine iodine of83.49,91.52,166.45μg/L in three group women classified as hardly,seldom and often intake of see food showed significant difference(X2=6.202,P<0.05).Urine iodine level in non-pregnant women taking seafood (90.94μg/L)was higher than that in pregnant women(84.79μg/L),the difference being statistically significant (U=3318.00,P<0.05).The urine iodine in pregnant women with seldom intake of seafood(94.46 μg/L)was significantly higher than that in the hardly intake women(83.28 μg/L),the difference being statistically significant (U=1257.5,P<0.05).During late period of gestation,the urinary iodine in the women ofthree statUS of hardly. Seldom and often intake of seafood were 81.93,97.97 and 140.18 μg/L,respective,with significant differences among them.Conclusions A certain amount of seafood taken every week Can increase urine iodine levels,and a direct relationship Was observed.Therefore,we suggest that it is necessary to advocate taking seafood to pregnant women for prevention of cretinism,particularly in the air.as where iodized salt was difficult to implement.

OBJECTIVETo investigate the expression of human annexin-V (HA-V) in relation to HBV infection in different fetal tissues.

METHODSImmunohistochemistry was employed to detect the expression and distribution of HA-V in the liver, kidney, ovary, heart, fallopian tube, spleen, and thymus gland of human fetus.

RESULTSHA-V expression was detected in different tissues including the ovary, liver, intrahepatic bile duct, heart, kidney, lymphocytic cells in the thymus gland, epithelial cells of the fallopian, and cortical and medullary cells of the spleen. HA-V was distributed mainly in the cytoplasm of the cells. The liver tissues exhibited greater gray scale for HA-V expression than in the other tissues (P<0.05) and no significant difference was observed in the other tissues than the liver (P>0.05) in image analysis with Photoshop 7.0.

CONCLUSIONHA-V is an inherent protein in fetal tissues with possible relation to HBV infection of different tissues as a HBV receptor. Greater amount of HA-V in the liver may account for the vulnerability of the liver to HBV infection.

Annexin A5 ; analysis ; Fetus ; chemistry ; virology ; Hepatitis B ; metabolism ; virology ; Hepatitis B virus ; growth & development ; Humans ; Immunohistochemistry ; Liver ; chemistry ; virology ; Tissue Distribution