With the change of medical mode and deepening of the medical education reforms,such educational idea as giving prominence to practice is widely used to improve students' comprehensive quality and innovative ability and practice ability. The medical shool of Tibet university has established long-term apprentice mechanism during the before class and playtimes and found four county hospitals, five health clinics in towns and townships and gradually improved the construction of mutual win-win 9clinical teaching bases. In this way it has been cultivating many advanced medical personnels, who are reliable, available, able to stay, and highly praised by the employers.

Pseudomonas aeruginosa is one of the most common causes of nosocomial infection due to its intrinsic resistance to antibiotics. In the host,glutathione(GSH) ,one of the most important intracellular antioxidants,provides protection against high levels of oxidative stress. A decrease in GSH levels in tissues infected with P. aeruginosa has been observed while interactions between pyocyanin and GSH maybe partially attribute to P. aeruginosa infection. In this review,the relationship between GSH and the pathogenicity of P. aeruginosa has been discussed based on the author's own research results and the latest literature.

OBJECTIVETo observe the release kinetics of methotrexate-loaded calcium phosphate cement (MTX-CPC) implanted in vivo and histologically investigate its resorption and osteogenesis.

METHODSMTX-CPC consisting of 1% methotrexate (MTX) (weight/weight) was pre-set and implanted into femoral muscles of 24 New Zealand rabbits. The in vivo MTX release kinetics was determined on the 1st, 2nd, 5th, 10th, 15th, 20th, 25th, and 30th post-implantation day. The local concentrations and the residual percentage of MTX were determined. Then the pre-set MTX-CPC was implanted into femoral condyle. Calcium phosphate cement (CPC) without MTX was used as a control. The femurs were harvested at the 1st day and the 1st, 3rd, and 6th month and examined by X ray. Then histomorphometric analyses including percentage of newly formed bone and amount of osteoblast and osteoclast were performed.

RESULTSThe MTX release kinetics in vivo confirmed that MTX-CPC was a monolithic matrix system, with a burst effect in the initial stage and a sudden drop thereafter. The local concentration of the released MTX was 0.372 μg/ml on the 30th post-implantation day; with a concentration higher than the effective concentration,the incorporated MTX was expected to be continuously released over the following 2-3 months. Both MTX-CPC and CPC showed good biodegradability and osteoconduction. Although the release of MTX had an inhibitory effect on osteogenesis, especially in the initial stage, the area of newly formed bone, the amount of osteoblasts, and the amount of osteoclasts were not significantly different between MTX-CPC group and CPC group on the 6th post-implantation month.

CONCLUSIONSMPX-CPC system is an effective drug delivery system. Both MTX-CPC and CPC has good biodegradability and osteoconduction. Therefore,MTX-CPC system can be an ideal material for filling defects and controlling local recurrence.

Animals ; Bone Cements ; Bone Regeneration ; Calcium Phosphates ; Methotrexate ; pharmacokinetics ; Osteogenesis ; Rabbits

OBJECTIVETo study the inhibitory effect of CD133 monoclonal antibody labeled with ¹³¹I (¹³¹I-CD133mAb) on Huh-7 human liver cancer cell line overexpressing CD133 antigen in vitro and in mouse models bearing the tumor cell xenograft.

METHODS¹³¹I-CD133mAb was prepared by chloramines-T method and evaluated for its stability. Flow cytometry and immunohistochemistry were used to detect the expression of CD133 in Huh-7 cells and in Huh-7 cell-derived tumors, respectively. Huh-7 cells treated with ¹³¹I-CD133mAb plus cisplatin (DDP), ¹³¹I -CD133mAb, DDP, or no treatment (blank control) were examined for cell proliferation suppression by MTT assay with the IC₅₀ calculated. BALB/c mice bearing subcutaneous Huh-7 cell xenograft in the right forelegs were treated with ¹³¹I -CD133mAb, DDP, or both every two days for two weeks. The tumor size and volume were measured twice a week, and pathological examination of the tumor was carried out after the treatments. The tumor inhibition rate was calculated and tumor cell apoptosis observed with HE staining.

RESULTSThe labeling ratio of ¹³¹I-CD133mAb was 90.25% and the radiochemical purity was 97.78%. Huh-7 cells showed obviously higher CD133 expression than HepG2 cells. ¹³¹I-CD133mAb combined with DDP group resulted in a significantly higher tumor inhibition rate than other treatments in the tumor-bearing mice.

CONCLUSION¹³¹I-CD133mAb can inhibit the growth of liver cancer cells with a high CD133 expression both in vivo and in vitro.

AC133 Antigen ; Animals ; Antibodies, Monoclonal ; pharmacology ; Antigens, CD ; immunology ; Apoptosis ; Carcinoma, Hepatocellular ; drug therapy ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cisplatin ; pharmacology ; Glycoproteins ; immunology ; Hep G2 Cells ; Humans ; Liver Neoplasms ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peptides ; immunology ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effect of amphotericinB (AmB) on migration and invasion of esophageal carcinoma Eca109 cells exposed to hypoxia and explore the molecular mechanisms.

METHODSRoutinely cultured esophageal carcinoma Eca109 cells were treated with 0, 1.25, 2.5, or 5 µg/ml AmB in hypoxic condition (3% O2, 5% CO2, and 92% N2) for 24 h. The cell migration and invasion were assessed by cell scratch test and Transwell chamber assay, respectively. Real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase-2 (MMP-2), and E-cadherin in the cells, respectively.

RESULTSCompared with the control cells, the cells treated with different doses of AmB showed attenuated ability of migration and invasion (P<0.05). AmB treatment resulted in significantly lowered mRNA and protein expressions of MMP-2 (P<0.05) and increased expressions of E-cadherin (P<0.05); the protein expression of HIF-1α decreased significantly in cells after AmB treatment (P<0.05) but its mRNA levels showed no significant changes (P>0.05).

CONCLUSIONAmB can suppress the migration and invasion of esophageal carcinoma Eca109 cells in hypoxic microenvironment possibly by regulating the expressions of HIF-1α, MMP-2 and E-cadherin.

Amphotericin B ; pharmacology ; Cadherins ; metabolism ; Cell Hypoxia ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Down-Regulation ; Esophageal Neoplasms ; metabolism ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; RNA, Messenger

Abstract: 【Objective】To study the effects of notoginsenoside R1 on the levels of intercellular adhesion molecule- 1（ICAM- 1），tumor necrosis factor- α （TNF- α），metalloproteinase- 2 （MMP- 2） and metalloproteinase- 2 inhibitor （TIMP- 2）in rats with atrial fibrillation in order to explore the mechanism of notoginsenoside R1 on the preventing and treating atrial fibrillation. 【Methods】 102 rats were randomly divided into control group ，atrial fibrillation group and notoginsenoside R1 group，with 34 rats in each group. The rat model of atrial fibrillation was established by injection of acetylcholine-calcium chloride into the tail vein. The rats in the notoginsenoside R1 group were intraperitoneally injected with 2 mL of notoginsenoside R1. ECG was used to measure the duration of atrial fibrillation. Masson staining was used to observe the degree of myocardial fibrosis. Immunohistochemistry was used to detect the expression of MMP-2 and TIMP-2 in atrial tissue. The serum ICAM-1，TNF-α，MMP-2 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay（ELISA）. The levels of ICAM-1，TNF-α and type I collagen in atrial tissue were determined by Western blotting.【Results】Before the treatment of notoginsenoside R1 ，there was no significant difference in the duration of atrial fibrillation between the two groups（P > 0.05）. After treatment，the duration of atrial fibrillation in the notoginsenoside R1 group［（6.37±2.02）s］was lower than that in the pre-treatment and the atrial fibrillation groups（P < 0.05）. Masson staining showed：the amount of atrial fibrillar collagen fibers in control group was normal；a large number of collagen fibers were seen in the atrial myocytes of atrial fibrillation group；the patchy and punctate collagen fibers were seen in the atrial myocytes of notoginsenoside R1 group. Compared with control group，the serum levels of ICAM-1，TNF- α and MMP-2 ［（137.52±16.59）10-6 g/L，（14.25±1.08）10-6 g/L，（435.26±17.63）10-9 g/L；（109.25±14.62）10-6 g/L ，（12.31±1.27）10-6 g/L， （288.47±15.52）10-9 g/L］were increased（P < 0.05），the serum levels of TIMP-2 levels［（3 541.27±331.24）10-9 g/L ； （3 975.46 ± 313.24）10- 9 g/L］was decreased（P < 0.05），the atrial tissue ICAM- 1，TNF- α and type I collagen levels （0.23±0.07 ，0.51±0.09 、0.63±0.14 ；0.15±0.06 ，0.22±0.07 ，0.27±0.12）were increased（P < 0.05），the atrial tissue MMP-2 protein optical density（0.35±0.07；0.18±0.06）was increased（P < 0.05），the atrial tissue TIMP-2 protein optical density（0.11±0.04；0.18±0.03）was decreased（P < 0.05）in atrial fibrillation group and the notoginsenoside R1 group； Compared with atrial fibrillation group，the levels of serum ICAM-1，TNF- α and MMP-2 were decreased（P < 0.05）， the levels of serum TIMP-2 was increased（P < 0.05），the atrial tissue ICAM- 1 ，TNF- α and type I collagen levels were decreased（P < 0.05），the density of MMP-2 protein in atrial tissue was decreased（P < 0.05），and the optical density of TIMP-2 protein in atrial tissue was increased（P < 0.05）in the rats in notoginsenoside R1 group.【Conclusion】 Notoginsenoside R1 can prevent and treat atrial fibrillation by reducing the levels of ICAM- 1，TNF- α and MMP-2 and increasing the levels of TIMP-2 in serum and atrial tissue of rats with atrial fibrillation.

OBJECTIVETo evaluate the safety of recombinant human interferon alpha-2b for nasal spray for the prevention of SARS and other upper respiratory viral infections.

METHODSField epidemiologic evaluation was conducted, the design was randomized and had a synchronously parallel control group. In the study, the drugs were given for five days and all subjects were followed up for ten days.

RESULTSDuring the period of using interferon, body temperature of the experimental group was normal compared to the control group. Experimental group had more influenza-like symptoms than the control group (P < 0.05), such as headache (4.83%-7.09%), dizziness (7.17%-11.63%), lassitude (8.55%-15.06%), muscular soreness (4.43%-7.09%), pharynx dryness (12.10%-17.85%), angina (6.25%-8.72%), abdominal pain (2.30%-5.50%) and diarrhea (2.45%-5.66%). Most of side effects reached their peak with in the first 3 days. Except for pharynx dryness, the incidences of all other side effects declined after completion of the use of the trial drug, and incidences of some symptoms in experimental group were lower than those of the control group. There were no significant differences in the symptoms of cough and expectoration between the experimental group and the control group. The incidence of exanthem in the control group was significantly higher than that in the experimental group. The side effect of bloody nasal mucus was not observed in experimental group, which had been reported by other authors in several volunteer studies.

CONCLUSIONUsing recombinant human interferon alpha-2b for nasal spray could lead to some influenza-like symptoms, however, all those symptoms were mild , reversible, and relieved after completion of the use of the trial drug. No serious side effects were found during the period of following up. The authors conclude that the drug is safe.

Abdominal Pain ; chemically induced ; Adolescent ; Adult ; Antiviral Agents ; administration & dosage ; adverse effects ; therapeutic use ; Dizziness ; chemically induced ; Female ; Follow-Up Studies ; Headache ; chemically induced ; Humans ; Interferon-alpha ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Recombinant Proteins ; SARS Virus ; drug effects ; Severe Acute Respiratory Syndrome ; prevention & control ; virology ; Treatment Outcome ; Young Adult

Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.

This study aims to investigate the regulatory effect of Sishen Pills(SSP) and its split prescriptions Ershen Pills(EP) and Wuweizi Powder(WP) on T follicular helper(Tfh) cell subset in the dextran sodium sulfate(DSS)-induced colitis mice and the mechanism. A total of 60 male SPF BALB/c mice were used, 10 of which were randomly selected as the normal group. The rest 50 were induced with 3% DSS solution for colitis modeling. After modeling, they were randomized into 5 groups: model group, SSP group, EP group, WP group, and mesalazine group. Body mass, colon mass, colon mass index, colon length, and unit colon mass index in each group were observed. After hematoxylin-eosin(HE) staining, the pathological injury of colon tissue was scored. The expression levels of molecules related to the STAT/SOCS signaling pathway in colon tissues were analyzed by Western blot. Differentiation levels of Tfh cells such as CD4~+CXCR5~+IL-9~+(Tfh9), CD4~+CXCR5~+IL-17~+(Tfh17), and CD4~+CXCR5~+Foxp3~+(Tfr) in peripheral blood of mice were detected by flow cytometry. The results showed each treatment group demonstrated significant increase in body mass and colon length, decrease in colon mass, colon mass index, unit colon mass index, and histopathological score(P<0.05, P<0.01), reduction of the expression of p-STAT3, STAT3, p-STAT6, and STAT6(P<0.05, P<0.01), rise of the expression of SOCS1 and SOCS3(P<0.05, P<0.01), decrease of Tfh9 and Tfh17 cells, and increase of Tfr cells(P<0.05, P<0.01) compared with the model group. These results indicated that SSP and the split EP and WP may alleviate ulcerative colitis by inhibiting the activation of STAT/SOCS signaling pathway and regulating the balance of Tfr/Tfh9/Tfh17 cells.
Animals ; Colitis/genetics* ; Colitis, Ulcerative/metabolism* ; Male ; Mice ; Mice, Inbred BALB C ; Prescriptions ; T-Lymphocytes, Regulatory

Aim To explore and verify the possible mechanism of Jiawei Duhuo Jisheng Mixture(JDJM)in the treatment on Knee Osteoarthritis(KOA)via using network pharmacology and animal experiment. Methods The ingredients of JDJM and relevant targets were collected from TCMSP and BATMAN-TCM database. The KOA-related targets were collected from GeneCard, OMIM and GEO databases. The common targets were acquired by intersecting ingredients-related and KOA-related targets, and then the Ingredient-Disease-Target Network and PPI network were constructed by Cytoscape 3.7.2 software and STRING platform. GO and KEGG enrichment analysis were performed based on Metascape database. Finally, the key targets and relevant mechanism were validated via animal experiment. Results In the network pharmacology study, 180 active ingredients related to treatment on KOA by JDJM were collected, and 152 common targets were confirmed. PPI network analysis showed that AKT1 might be the key targets of JDJM in the treatment on KOA. GO and KEGG enrichment analysis revealed that the key target mainly concentrated on inflammatory response and apoptosis. Animal experiment confirmed that JDJM could improve lesion in KOA rabbits, and suppress the expression levels of IL-1β, TNF-α, Caspase 3 and BAX in serum and articular fluid. AKT1 expression(including mRNA and protein)in articular cartilage was also down-regulated. Conclusions Based on the results of network pharmacology and animal experiment, JDJM may relieve KOA severity by anti-inflammatory and anti-apoptotic effects through a variety of molecular signaling pathways.