The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

AIM: To determine the effects of valsartan on calcium channel and sodium-calcium exchanger current in isolated ventricular myocytes of congestive heart failure (CHF) rats. METHODS: Eight weeks after coronary ligation, the rats with heart failure were confirmed by measuring the hemodynamic parameters and divided randomly into the group treating with valsartan (CHF-T, 20 mg/kg) and placebo (CHF-C). Sham-operated group rats served as negative controls (PS). Twelve weeks later, 6 rats were selected randomly for the study of ion channel. Single ventricular myocytes of rats were isolated by enzymatic dissociation. The whole-cell patch-clamp recording technique was used to record calcium channel current and sodium-calcium exchanger current. RESULTS: (1) In the hemodynamic variables, HR and blood pressure were not significantly different in three groups. Compared CHF-C with PS group, LVEDP and Cm increased, LVSP and ?d p /d t max decreased ( P 0 05). (4) Na +-Ca 2+ exchanger current in CHF-C group increased significantly. Na +-Ca 2+ exchanger current in CHF-T group was smaller significantly than that in CHF-C group. However, CHF-T group and PS group were not significantly different. CONCLUSION: Administration of valsartan is effective in preventing from cardiac function deterioration, increases calcium channel current and decreases Na +-Ca 2+ exchanger current in ventricular myocytes of heat failure rats.

Objective To investigate the relationship between the marrow edema and general clinical index,quadriceps muscle area,and the meniscus grade of knee osteoarthritis(OA).Methods 72 patients were collected with knee OA in our hospital, underwent X-ray and routine MRI examination of knee, and the same X-ray and MRI were reviewed at 12 months later in different time point.The K-L grading, bone marrow edema score, meniscal grading and VAS score of each knee joint were evaluated.The t-test and Rank-sum test were used to compare the two groups of general data, Spearman was used to perform bivariate correlation analysis.Results The age and VAS score of bone marrow edema group at the initial follow-up were significantly lower than those without edema group(P<0.05),the degree of marrow edema was moderately correlated with age and VAS score, and was not significantly correlated with other indexes.12 months later, BMI and the area of quadriceps femoris in the group with marrow edema were different from those in the group without bone marrow edema(P<0.05), the degree of marrow edema was moderately correlated with age, quadriceps area and VAS.Conclusion The range of marrow edema was related to age, quadriceps area, BMI index and VAS score in MRI.The MRI measurement could reflect the progression of knee OA more than that of X-ray.It also revealed some factors related to the progression of knee OA.

OBJECTIVETo study the relativity between Streptococcus sanguis group (SSG) and coronary heart disease (CHD).

METHODS41 individuals were diagnosed with CHD and 18 normals served as controls. All of them had undergone coronary angiography. Their social class (including education and wages), smoking, drinking, blood lipids and oral health were also recorded. SSG in saliva and subgingival plaque were cultivated in NAYS-B agar plates and counted. SSG were identified into species with routine biochemical reaction and AP-PCR.

RESULTSIn the multiple step regression analysis, the amount of SSG in saliva and subgingival plaque were positively associated with severe coronary atheromatosis after adjusting the classical risk factors of CHD. The average amount of SSG in saliva was (435 +/- 422) x 10(8) CFU/L in CHD group and (358 +/- 540) x 10(8) CFU/L in control group, F = 2.72, P = 0.08; the average amount of SSG in incisor was (331 +/- 484) x 10(7) CFU/L in CHD group and (98 +/- 164) x 10(7) CFU/L in control group, F = 5.54, P = 0.02; the average amount of SSG in molar was (352 +/- 381) x 10(7) CFU/L in CHD group and (185 +/- 232) x 10(7) CFU/L in control group, F = 2.86, P = 0.10. S. sanguis and S. gordonii were more in CHD group than in control group (P < 0.05), whereas S. mitis and S. oralis were the same in two groups (P > 0.05).

CONCLUSIONThe increase of SSG in oral floras may play an important role in the occurrence of CHD.

Aged ; Coronary Disease ; complications ; Dental Plaque ; microbiology ; Educational Status ; Gingiva ; microbiology ; Humans ; Middle Aged ; Molar ; microbiology ; Risk Factors ; Saliva ; microbiology ; Smoking ; Socioeconomic Factors ; Statistics as Topic ; Streptococcal Infections ; complications ; microbiology ; Streptococcus sanguis ; isolation & purification

We integrate web-based learning with team based learning,which is called WTBL method (Web-based and team-based Learning). WTBL method is constructed and applied to the teaching practice of core curriculum group courses of clinical medicine. We build some small private online courses. The students can preview online and do the case discussions by teamwork in class. The application of WTBL teaching method has realized the flipping of classroom, and helps to enhance students' self-learning ability and teamwork ability.

Objective:To detect the serum level of chitinase-3-like protein 1 (YKL-40) in patients with pemphigus vulgaris, and to analyze its correlation with the severity of pemphigus vulgaris.Methods:From January 2017 to May 2018, serum samples were collected from 38 patients with pemphigus vulgaris in Department of Dermatology, the Affiliated Hospital of Southwest Medical University, and those collected from 14 age-, gender- and body mass index-matched healthy volunteers served as controls. Serum levels of YKL-40 and Th1/Th2/Th17-related cytokines were detected by using Luminex ? 200 TM system. Mann-Whitney U test was used to compare serum levels of cytokines between the patient group and control group; binary logistic regression was used to investigate factors independently related to the severity of pemphigus vulgaris; a receiver operating characteristic (ROC) curve was drawn, and the area under the curve, sensitivity and specificity were calculated to evaluate the ability of YKL-40 to predict the severity of pemphigus vulgaris. Results:Compared with the control group, the patient group showed significantly increased serum levels of YKL-40 (expressed as median[ Q1, Q3]: 15.22 [14.19, 15.93] vs. 13.64 [13.21, 14.63]μg/L, z=-3.88, P < 0.05) , interleukin (IL) -6 (2.05 [1.49, 4.21] vs. 1.57[1.38, 1.75]ng/L, z=-2.44, P < 0.05) , IL-7 (7.45[5.63, 11.63] vs. 3.77[2.21, 5.97]ng/L, z=-3.26, P < 0.05], IL-8 (6.59[3.60, 14.73] vs. 4.36[2.96, 6.53]ng/L, z=-1.96, P < 0.05) , IL-2R-α (509.08 [386.36, 757.67] vs. 336.44[309.86, 458.71]ng/L, z=-2.35, P < 0.05) , and C5a (100.35 [78.31, 140.84] vs. 72.08 [37.23, 82.08] ng/L, z = -3.04, P < 0.05) . The concentration of serum YKL-40 gradually decreased along with the reduction of lesion areas ( r = 0.63, P < 0.001) , and YKL-40 was independently correlated with the severity of pemphigus vulgaris ( P = 0.025, OR = 46.54, 95% CI: 1.61, 1 347.19) . The area under the curve of YKL-40 was 0.783 (95% CI: 0.613, 0.953) for distinguishing between patients with severe to extremely severe pemphigus vulgaris and those with mild to moderate pemphigus vulgaris. Conclusion:The serum level of YKL-40 is strongly correlated with the severity of pemphigus vulgaris, and has a potential value in predicting the severity of this disease.

Objective:To study the effects of the combined application of NaF and Nisin on Streptococcus mutans(S.mutans).Meth-ods:The minimum inhibitory concentration(MIC)of Nisin and NaF against S.mutans was determined by microdilution method respec-tively.The fractional inhibitory concentration(FIC)was calculated by checkerboard method.The inhibition effect of the combination of NaF and Nisin at(NF)the same MIC concentration on acid production and acid resistance of S.mutans was detected.Crystal violet staining was used to detect the effects of NF in the inhibition of the biofilm formation,and the damage and dispersion of the established biofilms.The changes of the biofilms were observed by CLSM.Results:The MIC of NaF and Nisin was 0.6 mg/mL and 20 mg/mL re-spectively.The FIC was 0.75.The 1/8×MIC NF showed significantly higher inhibition on acid production and biofilm formation than 1/4×MIC NaF or Nisin(P＜0.05),but it has no obvious dispersion effect on established biofilms.The 1/2×MIC NF showed stronger in-hibition effect on the acid resistance of S.mutans in the membrane than 1×MIC NaF or Nisin(P＜0.05).At the concentration of 2x MIC,any component didn't cause obvious damage on the established biofilm structure.Conclusion:Nisin and NaF have synergistic in-hibitory effects on the proliferation,acid production,acid resistance and biofilm formation of S.mutans.

Objective To address the fall risks in surgical patients during different time of perioperative period, and explore the best time of risk assessment, and its influencing factors. Methods A total of 250 elderly, who had selective operation and were chosen by a convenient sampling method, received fall risk assessment by Johns Hopkins fall risk assessment tool. We assessed the fall risk factors once a day from the first day of hospitalization until the seven day after operation. Results The fall risk increased 1 d before operation, and it climbed the highest score on the operation day (13. 92 ± 1. 94) with statistical significant compared with fall risk of other day (P<0. 01). The average score of fall risk were (12. 87 ± 1. 42), (11. 98 ± 2. 15) in two days after operation having high fall risk. From 3 d to 7 d after operation, the score of fall risk maintained a medium level. By correlation analysis, it presented the Pearson coefficient was >0. 5, for medicine and nursing facilities of 3 d after operation, and the movement of Pearson coefficient was >0. 5 during the 2 d to 7 d after operation. The further outcome of regression analysis shew that medicine, movement, patient′s nursing facilities and the fall history were high risk factors during perioperative period. Conclusions The fall risk increases on one day before operation and reach peak when patients come back unit after operation. After 7 d operation, the score of fall risk decreases progressively, but it still stays at the medium level. Different time exists different high fall risk factors, and it indicates we should strengthen fall risk assessment and prevention at 1 d, day coming back unit after operation and 7 d after operation to prevent fall incidences.

Objective:To explore the standardization of totally implantable venous power port of nursing process in CT enhancement and application effect of contrast medium injection, so as to provide a safer and more efficient way for contrast medium injection in CT enhanced examination for patients with malignant tumors.Methods:A non-randomized prospective study was conducted, 358 patients with malignant tumors were selected in Sun Yat-sen Memorial Hospital, Sun Yat-sen University who underwent CT enhanced examination from August 1, 2022 to July 31, 2023, 179 patients who had been implanted totally implantable venous power port were selected as the experimental group, and the standardized nursing procedure was given. The other 179 patients were the control group, using radiology routine high-pressure intravenous indwelling needle as the contrast medium access, with routine peripheral venous nursing process. The incidence of contrast medium extravasation during CT enhanced examination was observed and compared between the two groups.Results:All the patients were included. There were 85 males and 94 females, aged (55.50±11.72) years old in the control group. There were 83 males and 96 females, aged (54.50±12.24) years old in the experimental group. The incidence of contrast medium extravasation was 0 in the experimental group and 3.35%(6/179) in the control group. The difference between the two groups was statistically significant (Fisher exact probability, P<0.05). Conclusions:The application of standardized nursing procedure of totally implantable venous power port to the injection of contrast medium in CT enhanced examination of malignant tumor patients, can significantly reduce the incidence of contrast medium extravasation.

In order to explore the role of BspE protein in Brucella infection,yeast two-hybrid tech-nique was used to screen host cell proteins that interact with BspE protein.The constructed BspE recombinant plasmid pGBKT7-BspE was used as bait plasmid to hybridize with the RAW264.7-cD-NA library of mouse mononuclear macrophages by yeast two-hybridization technique.The positive clones were extracted by plasmid,sequenced and co-immunoprecipitation to determine the host cell proteins that could interact with BspE.The subcellular localization of BspE proteins was analyzed by confocal laser microscopy.The physical and chemical properties,protein structure and function of BspE interacting proteins were analyzed by bioinformatics.The siRNA for one of the BspE inter-acting proteins was synthesized,the expression of its gene was silenced in HEK293T cells,and the silenced cells was infected with Brucella M5-90 and the number of intracellular bacteria was coun-ted.The results showed that the decoy plasmid pGBKT7-BspE was successfully constructed,and the plasmid could express BspE protein in yeast.Eight positive clones were obtained from the host cell genome library by yeast two-hybridization.The positive clones were identified as RBM27 and PCBP1 by sequencing,backcross and co-immunoprecipitation.Bioinformatics was used to predict the cell location,protein structure and amino acid composition of RBM27 and PCBP1.After siRNA interference,the expression level of PCBP1 was significantly decreased and the amount of M5-90 in the cell was increased.Brucellosis secreted protein BspE interacts with host proteins RBM27 and PCBPl,and PCBP1 negatively regulates the proliferation of Brucellosis.