Objective To investigate the genotypic characteristics of hepatitis B virus(HBV) in Tibet.Methods Serum samples from 60 cases of hepatitis B in Tibet Autonomous Region were collected from January 2000 to March 2004.HBV genotypes were analyzed by sequencing S region and precore/core region.Results HBV isolated from 60 cases were all found to be D genotype by S region sequencing.Dc mixture was found in 59 cases,showing the recombination between their precore/core gene and genotype B virus at 1804-2299 nucleotide.The other one case showed Dbc mixture genotype,showing recombination between its precore/core gene and genotype B and C genes.Conclusions All Tibet cases in this study show mixture genotype D with recombination with genotvpe C or both genotype B and C at precore/core region.No case of pure genotype D is found.

OBJECTIVE:To consummate the flow sheet in drug storehouse management so as to improve the management efficiency.METHODS:5S management,visible management and demand-oriented management stated in lean management were applied in drug storehouse management.RESULTS:Due to the application of the methods in lean management,the storage capability of hospital drug storehouse was increased,medicine circulation was accelerated,and the work efficiency was enhanced.CONCLUSIONS:The application of lean management theory is conducive to the upgrading of scientific management as well as the enhancing of both efficiency and performance of hospital drug management.

Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use.

Objective: To explore the relevant factors of acquired swallowing disorders in adult patients after cardiac surgery. Methods: A Jiatian water swallowing screening test was conducted for adult patients after cardiac surgery in our hospital from 2015-03 to 2015-09. There were 32 patients with acquired swallowing disorder deifned as Case group and meanwhile 420 patients without swallowing disorder at the same word deifned as Control group. Non-conditional Logistic regression analysis was applied to study the relevant factors for acquired swallowing disorders. Results: The overall incidence of acquired swallowing disorders was 7.08%. Multi Logistic regression analysis presented that duration of endotracheal intubation (OR=1.060,P<0.001), pre-operative arrhythmia (OR=2.780,P=0.019), NYHA grade (OR=1.789, P=0.033) and Euroscore (OR=1.216,P=0.040) were the relevant factors for the occurrence of acquired swallowing disorders in adult patients after cardiac surgery. Conclusion: Medical professionals should pay special attention to patients with above mentioned risk features at post-operative drinking to reduce the complications of acquired swallowing disorders.

Objective To investigate the effects of a novel synthetic immunostimulator CH2b containing thiazolidin-4-one on the function of invariant nature killer T (iNKT) cells isolated from patients with active rheumatoid arthritis (RA).Methods Peripheral blood mononuclear cells (PBMCs) isolated from patients with active RA were in vitro cultured with α-Galcer and IL-2.The iNKT cells were separated by using magnetic activated cell sorting (MACS) method.The effects of CH2b on the proliferation of iNKT cells were analyzed by using MTT assay.MILLIPLEX MAP Human Cytokine/Chemokine kit was used to measure the levels of IFN-γ and IL-4 in the supernatants of iNKT cell culture.The expressions of IFN-γand IL-4 at mRNA level in iNKT cells were analyzed by RT-PCR.Western blot assay was used to detect the levels of T-bet and GATA-3 in iNKT cells.Results CH2b significantly enhanced the proliferation of IL-2 activated iNKT cells isolated from the patients with active RA.CH2b promoted the secretion of IL-4,resulting in a decrease in the ratio of IFN-γ/IL-4.Moreover,CH2b promoted the expressions of GATA-3 and IL-4 at mRNA level in iNKT cells.Conclusion The novel immunostimulator,CH2b,might enhance the immunoregulatory effects of iNKT cells by promoting the GATA-3 pathway-mediated secretion of Th2-1ike cytokines and inducing the differentiation of Th0 to Th2 cells.

[ ABSTRACT] AIM:To establish an animal model of rheumatoid arthritis ( RA) in DBA/1 mice induced by im-munodominant mixed peptides derived from glucose-6-phosphate isomerase (GPI).METHODS: The DBA/1 mice were immunized with emulsified mixed peptide fragments of hGPI 325-339+hGPI469-483 or single peptide hGPI325-339 in com-plete Freund′s adjuvant by subcutaneous injection to induce the model of RA .Body weight , ankle joint symptom scores , the pathological change of the ankle joint , the levels of CD4 +T cells in the spleen and peripheral blood , the proportion of iNKT cells in the peripheral blood , and the levels of TNF-αand IL-6 in serum were detected to evaluate and analyze the model.RESULTS:The hind paw of the model mice appeared red swelling on the 8th day, and then aggravated gradually to the limbs.The red swelling reached peak on the 14th day, and then relieved gradually .Inflammation response dominated by lymphocytes and monocytes was observed in the ankle joint .The inflammatory effect of mixed peptides was more obvious than that of the single one (P<0.05).Compared with control group and the mice treated with single peptide , the weight gain was slow, the amount of CD4 +T cells in the peripheral blood and spleen were increased , the proportion of peripheral iNKT cells in the inflammatory peak was decreased (P<0.05), and the serum level of TNF-αwas increased significantly ( P<0.05) in the mice treated with mixed peptide fragments .CONCLUSION: The immunological characteristics of RA model induced by mixed GPI peptides in DBA/1 mice is closer to that in RA patients , especially in the immunopathology of iNKT cells.Therefore, this model can be used as a new tool for studying the mechanism and immunological intervention of RA.

Objective: To observe the efficacy and safety of analgesic drugs in the standardized treatment of cancer pain patients at the pain clinic. Methods: The data of 787 cancer pain patients and their corresponding prescriptions for cancer pain were collected from April, 2012 to April, 2013 at the pain clinic. The obtained information comprise of diseases that lead to cancer pain, cause of pain, pain intensity, and efficacy and side effects of medications. Diseases that caused cancer pain include 658 cases with primary malignant lung cancer. Results: Pain was mainly caused by primary lung cancer in 787 cancer-related patients. An analgesic drug, namely, oxycodone hydrochloride, was administered in 54.6% via single drug therapy. The daily dosage range of this drug was 20 to 90 mg/d in 280 cases. About 35.6% of the studied patients with a daily dosage of 90 mg/d or lower had their pain effectively managed. After the treatment, the number of cases with moderate to severe pain was reduced from 437 (55.5%) to 248 (31.5%). The oral administration of opioid oxycodone hydrochloride tablets ranked first among the prescribed drugs for cancer pain, and single-drug therapy was the choice of medication. The majority of patients had satisfactory pain-relief with a daily dosage of less than 90 mg/d upon the administration of oxycodone hydrochloride sustained-release tablets and morphine sulfate controlled-release tablets. Side effects included mild constipation, nausea, vomiting, dizziness, loss of appetite, urinary retention, somnolence, and so on. Intervention treatment was needed in most of the patients. Conclusion: Pain clinic is critical in the administration of standardized treatment for cancer pain in hospitals. The establishment of pain clinic ensures the standardized treatment of cancer pain.

Objective:To explore the effect of the synthetic immunomodulator CH 2b with a thiazolidin-4-one ring on the pathogenesis of rheumatoid arthritis (RA) mice induced by glucose-6-phosphate isomerase(GPI) mixed peptides.Methods:hGPI325-339 ,hGPI469-483 peptide fragments were mixed with complete freund′s adjuvant fully ,DBA/1 mice were givien subcutaneous injection of the emulsifiers,pertussis toxin to strengthen immunity.And then RA mice were intervened with α-GalCer and CH2b,the changes of body weight ,ankle joint symptoms scores were observed .The joint tissues stained with hematoxylin and eosin ( HE) was used to evaluate the inflammatory cells.Fluorescence-activated cell sorting ( FACS) was used to detect the frequency changes of iNKT cells .Cytometric bead array(CBA) was used to analyze the levels of serum cytokines TNF-α,IL-6,IL-4,IFN-γ.Results: Compared with the model group,α-GalCer,CH2b could reduce the inflammation of the model mice ,significantly improve the body weight growth and the joint swelling(P<0.05).The inflammatory cells infiltration were decreased.More importantly,CH2b improved the frequency of iNKT cells in peak,the difference was statistically significant (P<0.05).The levels of TNF-α,IL-6,IFN-γin serum were significantly decreased(P<0.05) by CH2b.α-GalCer,CH2b could decrease the levels of TNF-α,IL-6,IFN-γ,and the two groups had no statistically significant difference(P>0.05).Conclusion:Immunomodulator CH2b by activating iNKT cells affect the secretion of inflammatory cytokines ,and it relieved the GPI induced arthritis .

Objective To detect and analyze the percentages of CD4+T, CD8+T and invariant na-ture killer T ( iNKT) cells as well as iNKT subsets in different tissues and organs of non-obese diabetic (NOD)/LtJ mice before the onset and in the early and late stages of type 1 diabetes (T1D) for better under-standing the immune function in different disease stages. Methods Female NOD/LtJ mice were selected as experimental subjects. Their fasting blood glucose levels were measured by blood glucose meter. Glycosuria and blood glucose level ≥11. 1 mmol/L in two consecutive detections were used as the diagnostic criteria of T1D. These mice were divided into three groups as follows: non-onset, early stage and late stage groups. Changes in food and water intake, glucose level in the urine, body weight, mental state, fur color and urine volume were recorded. Percentages of CD4+T, CD8+T and iNKT cells and ratios of subsets in peripheral blood, thymus, spleen, liver and inguinal lymph nodes were detected by flow cytometry (FACS). Results (1) Compared with the non-onset and the early stage groups, mice in the late stage group were apathetic and had rough hair. Moreover, significantly increased water and food intake and urine output (P<0. 05) and de-creased body weight, thymus index, spleen index and the absolute lymphocyte counts of spleen, liver and thymus (P<0. 05) were observed in the late stage group. (2) Compared with the non-onset group, the early stage group showed significantly increased percentages of CD4+T cells in spleen, liver, thymus and inguinal lymph nodes (P<0. 05). Compared with the early stage group, the late stage group showed decreased per-centages of CD4+T cells in liver, thymus, inguinal lymph nodes and peripheral blood (P<0. 05). Compared with the non-onset group, the percentages of CD8+T cells in the early stage group were significantly increased in spleen and thymus, but reduced in inguinal lymph nodes (P<0. 05). Compared with the early stage group, the percentages of CD8+T cells in late stage group were significantly reduced in liver and thymus, but increased in inguinal lymph nodes (P<0. 05). (3) The percentages of iNKT cells in liver and inguinal lymph nodes of mice in the early stage group were significantly higher than those of the non-onset group (P<0. 05). The percentages of iNKT cells in peripheral blood and liver of mice in the late stage group were sig-nificantly lower than those of the early stage group (P<0. 05). No significant difference in the percentages of iNKT cells in spleen and thymus was found among the three groups (P>0. 05). (4) Compared with the non-onset group, the percentages of iNKT1 subset in thymus in the early and late stage groups were significantly increased, while the percentages of iNKT2 subset were significantly decreased (P<0. 05). No significant difference in the percentages of iNKT1 and iNKT2 subsets in spleen, liver and inguinal lymph nodes was found among the three groups (P>0. 05). (5) The percentages of iNKT2 subset in spleen, liver and ingui-nal lymph nodes were significantly lower than those of the iNKT1 subset in the three groups (P<0. 05). The percentage of iNKT2 subset in thymus was significantly higher than that of iNKT1 subset in the non-onset group (P<0. 05). (6) Compared with the non-onset and the late stage groups, the early stage group showed significantly increased levels of IFN-γ, IL-4 and IL-17A and up-regulated ratio of IFN-γ/IL-4 (P<0. 05). Compared with the non-onset and the early stage groups, the late stage group showed significantly increased IL-6 level (P<0. 05). Compared with the non-onset group, IL-10 level in the other two groups was in-creased, especially in the late stage group (P<0. 05). No significant difference in IL-2 level was found among the three groups (P>0. 05). Conclusion Increased percentages of iNKT cells and iNKT1 subset in NOD/LtJ mice with early stage of T1D might be involved in the development of T1D.

Objective:To investigate the effect of different delivery and feeding modes on intestinal microflora in infants with atopic dermatitis (AD) .Methods:A total of 33 infants with AD were enrolled from Department of Dermatology, Wuhan NO.1 Hospital from July 2019 to December 2020, and 30 healthy infants were selected as control group. Then, all infants were grouped according to different delivery and feeding modes: cesarean-delivery AD group (22 cases) , cesarean-delivery control group (19 cases) , spontaneous-delivery AD group (11 cases) , and spontaneous-delivery control group (11 cases) ; mixed-feeding AD group (13 cases) , mixed-feeding control group (11 cases) , formula milk powder-feeding AD group (12 cases) , formula milk powder-feeding control group (11 cases) , breastfeeding AD group (8 cases) , and breastfeeding control group (12 cases) . The total DNA was extracted from the infant feces, PCR was performed to amplify the V1 - V9 regions of bacterial 16S rRNA gene, and PacBio Sequel sequencer was used for high-throughput sequencing. Wilcoxon rank sum test was used to compare the bacterial community composition at genus and species levels, and correlations of relative abundance of differentially abundant bacterial taxa with eosinophil counts and SCORing Atopic Dermatitis (SCORAD) scores were analyzed.Results:In the spontaneous-delivery control group, cesarean-delivery control group, spontaneous-delivery AD group, and cesarean-delivery AD group, the top 5 bacterial genera with high relative abundance were Bifidobacterium, Bacteroides, Veillonella, Streptococcus, and Escherichia. In the formula milk powder-feeding control group, breastfeeding control group, mixed-feeding control group, formula milk powder-feeding AD group, breastfeeding AD group, and mixed-feeding AD group, the top 5 abundant bacterial genera were Bifidobacterium, Bacteroides, Clostridium, Veillonella, and Escherichia. Linear discriminant analysis of effect size (LEfSe) showed no significant difference in the relative abundance of bacterial taxa among different delivery mode groups; among different feeding mode groups, Akkermansia and Akkermansiamuciniphila were the most differentially abundant microbes in the formula milk powder-feeding AD group at genus (LDA = 4.78) and species (LDA = 4.91) levels, respectively. The relative abundance of Akkermansia and Akkermansiamuciniphila (both 9.6% ± 0.72%) was significantly higher in the formula milk powder-feeding AD group than in the formula milk powder-feeding control group (both 2.50% ± 0.83%, Z = 1.66, P = 0.048) , the mixed-feeding AD group (both 0, Z = 2.26, P = 0.012) and the breastfeeding AD group (both 0, Z = 1.85, P = 0.032) . Additionally, the relative abundance of Akkermansia and Akkermansia- muciniphila was positively correlated with SCORAD scores in AD patients ( ρ = 0.384, 0.387, respectively, both P < 0.05) . Conclusion:Different delivery modes did not significantly affect the intestinal flora of AD or healthy infants, and the relative abundance of Akkermansia and Akkermansiamuciniphila increased in the formula milk powder-feeding infants with AD, which may be involved in the occurrence of AD.