The modulation and mechanisms of high-altitude hypoxia in drug transport across the blood-brain barrier / 药学学报

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.

Comparison of the predictive value of anthropometric indicators for the risk of benign prostatic hyperplasia in southern China / 亚洲男科学杂志(英文版)

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759-0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753-0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723-0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609-0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587-0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540-0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Effect and Mechanism of Sulforaphane on G / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of sulforaphane (SFN) on G@*METHODS@#KG1a and KG1cells were treated by different concentrations of SFN for 48 h. Flow cytometry (FCM) was used to analyze the phase distribution of cell cycle. High-throughput sequencing was used to detect the effect of SFN on the expression of cell cycle related genes in KG1a cells. The mRNA expression of P53, P21, CDC2 and CyclinB1 were detected by qPCR. The protein expression of P53, CDC2, P-CDC2 and CyclinB1 were detected by Western blot.@*RESULTS@#Cells in the G@*CONCLUSION@#SFN induces leukemia cells to block in G

Changes in the intestinal flora of rats under high altitude hypoxia / 药学学报

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.

Effect of hypoxia on drug metabolizing enzymes and transporters and the role of microRNA / 药学学报

The function of circulatory system, nervous system and endocrine system is significantly changed in hypoxic environments. These changes affect the absorption, distribution, metabolism, and excretion of drugs in the body. Drug metabolizing enzymes and transporters are the main factors affecting drug metabolism; microRNA (miRNA) can act directly on drug metabolizing enzymes and transporters and can regulate their genes through hypoxia-inducible factor, inflammatory cytokines, and nuclear receptors. This article reviews the effect of hypoxia on drug metabolizing enzymes and transporters and the mechanisms by which miRNA modulates these proteins and their expression during hypoxia.

Simultaneous Determination of Seven Constituents in Qinggan Lidan Mixture by HPLC / 中国实验方剂学杂志

Objective: To establish an HPLC method for simultaneous determination of geniposide,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,isochlorogenic acid A,B and C in Qinggan Lidan mixture,in order to provide references for its quality control. Method: The analysis of methanol extract of this drug was performed on a 35℃ Luna C18 column (4.6 mm×250 mm,5μm),with the mobile phase comprised of acetonitrile-0.4% phosphoric acid flowing at 1.0 mL·min-1 in a gradient elution mode (0-10 min,8%-12%A;10-30 min,12%A;30-60 min,12%-35%A),and the detection wavelengths were set at 238 and 327 nm. Result:Geniposide,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,isochlorogenic acid A,B and C were completely separated,and well separated from other constituents. The linear ranges of geniposide,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,isochlorogenic acid A,B and C were 0.188-2.355,0.083-1.040,0.074-0.920,0.075-0.940,0.064-0.800,0.076-0.955,0.071-0.888 μg (r ≥ 0.999 0),respectively. The average recoveries were 99.45%,98.45%,99.06%,98.50%,98.16%,101.01%,96.93%,with the RSDs of 0.5%,1.8%,1.3%,2.4%,2.3%,1.6%,1.6%,respectively.The contents of geniposide,chlorogenic acid,neochlorogenic acid,cryptochlorogenic acid,isochlorogenic acid A,B and C were 3.420-3.794,0.835-0.890,1.222-1.275,1.064-1.210,0.377-0.398,0.419-0.464 and 0.362-0.405 g·L-1,respectively. Conclusion:This method can be used for simultaneous determination of muti-ingredients in Qinggan Lidan mixture,and the established method is simple and accurate,with a good reproducibility and high sensitivity. It can be used for the quality control of Qinggan Lidan mixture.

Roles and mechanisms of traditional Chinese medicine and its active ingredients in treating epilepsy / 中国中药杂志

At present,Western medicine is widely used in the treatment of epilepsy.However,about 30%-40% of epileptic patients are resistant to them and are affected by the side effects of these drugs.Traditional Chinese medicine is effective in treating epileptic seizures and relieving complications caused by Western medicine.However,the active ingredients and mechanisms of traditional Chinese medicine remain unclear.This article reviews and summarizes the advances and mechanisms in treating epilepsy,such as Chinese medicine monomer,the extracts of single Chinese medicine and Chinese medicine compound.Chinese medicine monomers,including gastrodin,asarone,rhynchophylline,ligustrazine,tanshinone ⅡA,curcumin,etc.,have antiepileptic effects via regulating excitatory neurotransmitters and receptors,the expression of inflammatory factors,sodium/potassium ion channels and the expression of apoptotic protein,therefore protecting neurons.The extracts of single Chinese herbal including the extracts of Gastrodiae Rhizoma,Acori Tatarinowii Rhizoma,Ginseng Radix et Rhizoma,Ganoderma,Scutellariae Radix and Ginkgo Folium,etc.,have antiepileptic effects related to the inhibition of γ-aminobutyric acid receptor,upregulation of phosphatidylinositol 3-kinase signaling pathway and reduction of glutamate-induced excitotoxicity and oxidative stress response.Furthermore,these extracts can regulate ion channels and reduce oxidative damage of neurons.Chinese medicine compounds including Dianxian Qing Granules,Danxing Ningxian Granules,Huoxue Dingxian formulae,etc.,can improve the therapeutic effect on epilepsy through simultaneously regulating excitatory transmitters,apoptosis factors and cytokines.

Progress on Detection of Metals Ions by Functional Nucleic Acids Biosensor / 分析化学

Functional nucleic acids are natural or artificialnucleic acid sequences with specific functions and special structures. Special metal ions are essential trace elements for human health, but excessive metal ions will be harmful to human health. The functional nucleic acids are widely used in the detection of metal ions because of their advantages such as easy modification, low price, high stability and strong specificity. This review describes the function of functional nucleic acid and metal ions, mainly including cutting type, link type, metal ion-mediated base pairing, click chemical type, conformation change type, and other types. Then, biosensor of functional nucleic acid combined with different signal output is introduced. Finally, the research significance and problems of functional nucleic acid in metal ion detection are discussed, and the future development direction and application prospect of functional nucleic acid biosensor are prospected.

Establishment and Application of Functional Nucleic Acid Biosensor for Detection of Mercury Ion / 分析化学

Excessive mercury ions have negative effects on individual health. So, it is of great significance to develop a method for rapid, sensitive and specific detection of Hg2+. In this study, the method for detection of Hg2+ was developed based on specific T-Hg-T mismatche and G-quadruplex. The template sequence mainly included the recognition region which could combine with Hg2+ specifically, the rich G region which could form G-quadruplex, and the speacer 18 partition zone. The target sequence mainly included 5' ends combining area and 3' end T-rich region. Templates and targets could be combined and the elongation was triggered only in the presence of Hg2+. Furthermore, the G-rich sequences were stripped off the templates and could form a single-stranded structure, because Spacer 18 had partition function. The G-quadruplex was formed with the K+and hemin, and catalyzed H2 O2-2,2-azinobis (3-ethylbenzothiozoline)-6-sulfonic acid(ABTS) reaction with color variations. The detection could be done within 35 min, and the Hg2+ concentration exhibited a linear correlation with absorbance at 414 nm within range of 20-500 nmol/ L, with a detection limit of 16. 5 nmol/ L (3σ). The recoveries of Hg2+ spiked in tap water were 98. 5％ - 103. 5％ . The method exhibited the advantages such as simple operation, low cost and short time, and operation value in emergency treatment and real-time environmental detection.

Replenishment of intestinal stem cells during the repair of radiation-induced intestinal injury / 中国组织工程研究

BACKGROUND:Radiation-induced intestinal injury causes a sharp reduction in the number of intestinal stem cells (ISCs) and their dysfunction.This brings great challenges in the repair of injured intestinal epithelium.Prompting restoration of the number and function of ISCs is a highlight of current research in the treatment of radiation-induced intestinal injury as well as in the repair of injured intestinal epithelium.OBJECTIVE:To review the latest progress in the pathway and mechanism of ISCs replenishment after radiation-induced intestinal injury.METHODS:The first author searched the CNKI,Wanfang and PubMed databases using the keywords of “intestinal stem cell,radiation-induced intestinal injury” in Chinese and English,respectively,to retrieve relevant articles published from January 2010 to June 2016.Then we generalized and summarized the results of these articles.RESULTS AND CONCLUSION:The fate of ISCs is regulated by various signal pathways,mainly including Wnt/β-catenin,BMP,Notch and EGF pathways.Early secretory progenitors (ESPs) are relatively quiescent during homeostasis,and insensitive to radiation injury;moreover,the ESPs can convert to ISCs under certain conditions.So,they are desired source of “reserve stem cells”.Stem cell niche plays an important role in reverse differentiation from ESPs to ISCs,but the exact regulatory mechanism remains largely unknown.Investigation on the above mechanism is of important scientific significance for deeply understanding the restoration process after radiation-induced intestinal injury and thus actively regulating intestinal injury repair.

A review of radiation impact on drug metabolism / 药学学报

The radiation is regarded as the fourth biggest pollution following the water, air and noise pollution, which generates a broad impact on human physiology and healthy. The radiation mainly comes from medical rays, industrial rays, nuclear wastes and atmospheric ultraviolet rays. The universality makes people pay more and more attention to the damage effect and mechanism of radiation. The radiation is divided into ionizing and non-ionizing radiation. It is a good idea to study the effect of ionizing and non-ionizing radiation on drug's metabolism, which may give a guidance to clinical medication to avoid adverse reactions and to support personalized medicine. This article reviews the effect of ionizing radiation (γ-rays, X-rays, uranium and cesium) and non-ionizing radiation (ultraviolet rays) on drug metabolism, their impact on metabolic characteristics of some drugs and the impact on expression of enzymes and transporters in drug metabolism, which is conducted with a focus on clinical significance.

A review of drug metabolism under hypoxia environment at high altitude / 药学学报

The special environmental features of high altitude, such as hypobaric hypoxia, low temperature, arid, high solar radiation, variable climate and geochemical anomaly, cause great effects on human physiology and health. It will provide valuable references and new ideas to study drug's metabolism in special environment of high altitude hypoxia, and give the guidance to clinical reasonable medication, avoiding adverse reactions and personalized medicine in plateau areas. This article reviewed the effect of high altitude hypoxia on drug metabolism, elaborated metabolic characteristics of some drugs and the activity and expression of drug metabolism enzymes under hypoxia environment at high altitude, and discussed related mechanism.

Diatoms in drowned and postmortem immersed rabbits' lungs / 法医学杂志

OBJECTIVE@#To investigate the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs.@*METHODS@#Sixty-two rabbits were randomly divided into drowning group (n = 30), postmortem immersion group (n = 30) and land death group (n=2), and the diatoms in each lung lobe were analyzed quantitatively and qualitatively by microwave digestion and scanning electron microscopy.@*RESULTS@#In the drowning group, the diatoms were detected in each lung lobe with Cyclotella and Melosira in the majority. In the postmortem immersion group, Cyclotella was in the majority. And the diatoms weren't detected in some lung lobes in postmortem immersion. There were significant differences in the detection rates of upper lobe of left lung, middle lobe and cardiac lobe of right lung in two groups (P < 0.05).@*CONCLUSION@#Based on the microwave digestion and scanning electron microscopy, the numbers, sizes and types distribution of diatoms in drowned and postmortem immersed rabbits' lungs can be analyzed and used as references for testing theory.

Effect of Tibetan medicine zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2 / 药学学报

To study the effect of Tibetan medicine Zuotai on the activity, protein and mRNA expression of CYP1A2 and NAT2, three different doses (1.2, 3.8 and 12 mg x kg(-1)) of Zuotai were administrated orally to rats once a day or once daily for twelve days, separately. Rats were administrated orally caffeine (CF) on the second day after Zuotai administration, and the urine concentration of CF metabolite 5-acetylamino-6-formylamino-3-methyl-uracil (AFMU), 1-methyluric acid (1U), 1-methylxanthine (1X), 1, 7-dimethylxanthine (17U) at 5 h after study drug administration was determined by RP-HPLC. The activity of CYP1A2 and NAT2 was evaluated by the ratio of metabolites (AFMU+1X+1U)/17U and the ratio of AFMU/(AFMU+1X+1U), respectively. The protein and mRNA expression of CYP1A2 and NAT2 were determined by ELISA and RT-PCR method, respectively. After single administration of Zuotai 3.8 mg x kg(-1) and repeated administration of Zuotai 3.8 and 12 mg x kg(-1), the activity of CYP1A2 and NAT2 decreased significantly compared with control group and there was no significant difference between other dose group and control group. The protein expression of CYP1A2 was significant lower than that in control group after repeated administration of Zuotai 12 mg x kg(-1), and the mRNA expression of CYP1A2 decreased significantly compared with that of control group after single administration of Zuotai 3.8 mg x kg(-1) and repeated admistration of Zuotai 12 mg x kg(-1), separately. The protein expression of NAT2 decreased significantly compared with that of control group after single and repeated administration of Zuotai 3.8 mg x kg(-1), respectively, and the mRNA expression of CYP1A2 decreased significantly compared with control group after single administration of Zuotai 3.8 mg x kg(-1). This study found that Tibetan medicine Zuotai had significant effect on the activity, protein and mRNA expression of CYP1A2 and NAT2.

Effects of p38MAPK inhibitor on the occurrence of acute GVHD and intestine damage after allogeneic hematopoietic stem cell transplantation in mice / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effects of p38MAPK inhibitor SB203580 (SB) on the occurrence of acute GVHD and intestine damage after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in mice.</p><p><b>METHODS</b>Sixty BALB/c mice, as recipients, were randomized to control group, irradiation group, model group and intervention group. C57BL/6 mice, as donors, were raised to prepare the bone marrow cells (BMCs) and spleen cells (SCs), which were injected into irradiated recipients mice by tail vein. Except control group, other groups accepted 7.5Gy total body irradiation. Model group and intervention group were infused with BMCs 5×10⁶ and SCs 5×10⁵ by less than 4 h after irradiation. SB was injected into intervention group by intraperitoneally, but only DMSO for model group. The general status and survival rate of each group were evaluated. The expression of p-p38MAPK, Fas and FasL in intestine were determined by RT-PCR, Western blot and immunohistochemistry (IHC).</p><p><b>RESULTS</b>The weight changes of intervention group (13.00±0.50)% was significantly lighter than that of model group (25.00±0.75)% (P<0.05). The clinical score of acute GVHD in the intervention group (3.33±0.82) was significantly lower than that of model group (6.33±1.36) (P<0.05). The expression levels of p-p38MAPK, Fas and FasL in small intestine of intervention group (1.43±0.02, 0.81±0.03, 0.97±0.03) were lower than those of model group (1.76±0.05, 1.52±0.04, 1.48±0.04).</p><p><b>CONCLUSION</b>SB inhibited the activation of p38MAPK and Fas/ FasL signal pathway and alleviated the apoptosis of small intestine. And SB could relieve small intestine damages induced by allogeneic T lymphocytes.</p>

Relationship between programmed death-ligand 1 and clinicopathological characteristics in non-small cell lung cancer patients / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics.</p><p><b>METHODS</b>From 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using χ(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages.</p><p><b>RESULTS</b>Positive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021).</p><p><b>CONCLUSION</b>PD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.</p>

New percutaneous absorption herbal patch for asthma of paracmasis and its effect on the relative transcription factors of patients / 中国针灸

<p><b>OBJECTIVE</b>To observe the therapeutic effect and mechanism of new percutaneous absorption herbal patch for asthma of paracmasis, and to optimize the form of the patch.</p><p><b>METHODS</b>One hundred and twenty cases of paracmasis asthma were randomly divided into medicine patch group, medicinal vesiculation group and western medication group with 40 cases for each. The new percutaneous absorption herbal patch was applied on medicine patch group. Traditional medicinal herbs cake of the hospital were applied on medicinal vesiculation group. Feishu (BL 13), Fengmen (BL 12) and Dazhui (GV 14) were adopted for both groups. Each patch was applied for 6 hours and once every other day. Accuhaler was applied on the western medicine group with 2 inhalations a time and twice a day. Clinical symptom scores, number of attacks and asymtomatic days were observed right before, after and half a year after the treatment. Meanwhile, the expression level of IgE, IL-4, GATA-3 mRNA and T-bet mRNA were observed and compared before and after the treatment.</p><p><b>RESULTS</b>Clinical symptom scores of all the 3 groups were improved (all P < 0.01). The differences of the total effective rate, number of attacks and asymtomatic days of all the 3 groups are without statistical significance (all P > 0.05). However, the long-term therapeutic effect in half a year after the treatment showed that the total effective rate of the medicine patch group was 80.0% (32/40), and the medicinal vesiculation group was 70.0% (28/40). Both of the them were obviously higher than 47.5% (19/40) of the western medicine group (P < 0.01, P < 0.05). And the medicine patch group surpassed the other 2 groups in controlling the number of attacks and increasing the asymtomatic days (P < 0.05, P < 0.01). The level of IgE and IL-4 of all the 3 groups decreased sharply after the treatment (P < 0.05, P < 0.01). And there was no statistic significance in differences among groups (all P > 0.05). The level of GATA-3 mRNA was obviously decreased, while the level of T-bet mRNA was obviouly increased in the medicine patch and medicinal vesiculation groups (P < 0.05, P < 0.01). And the medicine patch group had obvious superiority on increasing the level of T-bet mRNA when compared with the medicinal vesiculation and western medicine groups (P < 0.01, P < 0.05).</p><p><b>CONCLUSION</b>It is concluded that the new percutaneous absorption herbal patch has exact effect on asthma. The treatment may reverse the imbalance condition of Th1/Th2 through regulation on cell factor and its specific transcription factors.</p>

Effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19 / 药学学报

This study is to investigate the effect of high altitude hypoxia on the activity and protein expression of CYP2C9 and CYP2C19. Rats from plain (P) and rats with acute middle altitude hypoxia (AMH), chronic middle altitude hypoxia (CMH), acute high altitude hypoxia (AHH) and chronic high altitude hypoxia (CHH) were administered orally phenytoin sodium (PHT) and omeprazole (OMZ) to evaluate the activity of CYP2C9 and CYP2C19, separately. The serum concentrations of PHT and metabolite 4'-hydroxyphenytoin (HPPH) at 12 h after treatment and the serum concentrations of OMZ and metabolite 5-hydroxy omeprazole (5-OHOMZ) at 3 h after treatment were determined by RP-HPLC. The activity of CYP2C9 and CYP2C19 was evaluated by the ratio of HPPH to PHT and the ratio of 5-OHOMZ to OMZ, respectively. The protein expressions of CYP2C9 and CYP2C19 were determined by ELISA method. The activities of CYP2C9 (HPPH/PHT) in P, AMH, CMH, AHH and CHH were 0.67 +/- 0.31, 0.75 +/- 0.29, 0.76 +/- 0.23, 0.79 +/- 0.31 and 0.75 +/- 0.18, respectively, and the activities of CYP2C19 (5-OHOMZ/OMZ) in P, AMH, CMH, AHH and CHH were 0.17 +/- 0.06, 0.20 +/- 0.10, 0.11 +/- 0.05, 0.37 +/- 0.13 and 0.19 +/- 0.05, respectively. The protein expressions of CYP2C9 in P, AMH, CMH, AHH and CHH were 4.20 +/- 1.27, 3.95 +/- 0.81, 3.93 +/- 1.11, 4.32 +/- 1.03 and 4.12 +/- 0.86 ng x g(-1), respectively, and the protein expressions of CYP2C19 in P, AMH, CMH, AHH and CHH were 3.91 +/- 1.82, 3.63 +/- 2.07, 2.55 +/- 0.85, 4.78 +/- 2.37 and 3.51 +/- 1.03 ng x g(-1), respectively. The activities and protein expressions of CYP2C9 in AMH, CMH, AHH and CHH were not significantly different with those of P. The protein expressions of CYP2C19 in AMH, CMH, AHH and CHH were not significantly different with those of P, but the activity of CYP2C19 in AHH was significantly higher than that of P. This study found significant changes in the activity of CYP2C19 under the special environment of acute high altitude hypoxia.

Effect of recipient mouse age on occurrence of graft-versus-host disease following allogenic bone marrow transplantation / 中国实验血液学杂志

This study was aimed to explore the influence of recipient age on the occurrence of acute graft-versus-host disease (aGVHD) in mice. 8 - 10 weeks aged C57BL/6 (H-2K(b)) mice were selected as donors, 18 - 20 weeks aged and 8 - 10 weeks aged BALB/c (H-2K(d)) mice were served as recipients. 18 - 20 weeks and 8 - 10 weeks aged mice were all randomly divided into three groups: normal control group (without any treatment); irradiation alone group [administered a total body irradiation (TBI) without bone marrow transplantation] and model group [infused with bone marrow mononuclear cells 5 × 10(6) and splenocytes 5 × 10(5) from donor C57BL/6 (H-2K(b)) mice through caudal vein no more than 4 h after TBI]. The general state and survival rate of all mice were observed everyday. The factors (the chimerism in peripheral blood, T lymphocyte and their subsets, the percentage of Th1 cells) of mice in model groups were measured by flow cytometry on day 5, 10, 15, 20, 25, 30 after TBI, the leukocytes in peripheral blood were also calculated by direct microscopic counting. The histological examinations of liver, intestine and skin were done by hematoxylin and eosin staining on day 5, 15, and 25 after TBI. All above data were compared between model groups. The results indicated that murine model with aGVHD was established in two model groups. Compared with 8 - 10 weeks aged mice, the 18 - 20 weeks aged mice showed higher survival rate and lower clinical scores (P < 0.05); the reconstitution time of leukocyte and chimerism in peripheral blood were delayed (P < 0.05); The ratio of CD8(+)T lymphocytes and Th1 cells in peripheral blood were lower (P < 0.05); the histological changes of liver, intestine and skin were little. It is concluded that 18 - 20 weeks aged recipient mice exhibited a lower incidence of aGVHD than 8 - 10 weeks aged recipient mice.

Pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain and in native Han and Tibetan healthy volunteers living at high altitude / 药学学报

The paper is to report the pharmacokinetics of sulfamethoxazole in healthy Han volunteers living at plain (PH) and native Han and Tibetan healthy volunteers living at high altitude (HNH and HNT). After healthy volunteers were administrated orally cotrimoxazole tablets, plasma concentration of sulfamethoxazole and metabolite N4-acetylsulfamethoxazole was determined by RP-HPLC, and plasma concentration-time data were analyzed by DAS 2.0 software to get the related pharmacokinetic parameters. The main pharmacokinetic parameters t(1/2) of sulfamethoxazole in PH, HNH and HNT were, respectively, 9.30 +/- 1.11, 10.99 +/- 1.23 and 10.44 +/- 1.05 h; tmax were 1.4 +/- 0.3, 2.0 +/- 1.1 and 1.8 +/- 0.4 h; Cmax were 94.42 +/- 15.26, 89.33 +/- 7.67 and 87.43 +/- 11.61 micro x mL(-1); AUC(0-t) were 1202.5 +/- 238.3, 1 434.7 +/- 193.9 and 1302.8 +/- 103.0 microg x h x mL(-1); AUC(0-infinity) were 1240.7 +/- 255.3, 1511.5 +/- 211.9 and 1363.9 +/- 116.5 microg x h x mL(-1); CL were 1.01 +/- 0.22, 0.81 +/- 0.12 and 0.89 +/- 0.08 L x h(-1) x kg(-1); V were 13.27 +/- 1.73, 12.81 +/- 2.15 and 13.28 +/- 1.20 L x kg(-1). Sulfamethoxazole pharmacokinetic parameters of HNH and HNT were significantly different from that of PH. The t(1/2) was significantly higher and the CL was significantly lower in HNH and HNT than that in PH, and the AUC(0-infinity) was significantly lower in HNT compared with HNH. This study found significant changes in the disposition of sulfamethoxazole under the special environment of high altitude hypoxia. This finding may provide some references for clinical rational application of sulfamethoxazole in HNH and HNT.