The nitric oxide donor drugs have the functions of anti-hyperplasia, inhibiting platelet adhesion and aggregation, regulating immune response, etc. It suggests that these drugs play important roles in therapy of cardiovascular diseases, male impotence and pregnancy-induced hypertension syndrome.

Objective:To develop an HPLC method for the determination of nintedanib in rabbit plasma and study the pharmacoki-netics of nintedanib in rabbits. Methods:The separation was performed on an Agilent ZORBAX SB-C18 column. A mixture of acetoni-trile-0. 1% trifluoroacetic acid-water (35∶ 20∶ 45) was used as the mobile phase at a flow rate of 1. 0 ml·min-1. The detection wavelength was set at 286 nm. Carbamazepine was used as the internal standard and nintedanib was extracted by ethyl acetate from plasma under basic condition. Totally 6 rabbits were given 20 mg·kg-1 nintedanib with intravenous administration. The blood samples were collected from the auricular vein at different time points after the administration. The concentration of nintedanib in plasma was detected by the HPLC method. The pharmacokinetics parameters were analyzed by DAS program. Results: An excellent linear rela-tionship was obtained within the range of 0. 05-10. 00 μg·ml-1(r=0. 999 8). The intra-day RSD was 5. 55%, 4. 53% and 2. 74%and inter-day RSD was 6. 15%, 5. 45% and 3. 15%, respectively for the three concentrations(0. 10, 2. 50 and 7. 50μg·ml-1), and the relative recovery was (98. 50 ± 5. 47)%, (100. 25 ± 4. 54)% and (99. 94 ± 2. 74)%, respectively. The main pharmacokinetics parameters of nintedanib were as follows: Cmaxwas (3.01 ±0.35) μg·ml-1, t1/2 was (4.38 ±1.53) h and AUC0-t was (11.67 ± 1. 71) μg·h·ml-1 . Conclusion:The method is simple, rapid and accurate, and can be used to determine the nintedanib concentra-tion in rabbit plasma and study its pharmacokinetics. Nintedanib is fitted the first-order elimination kinetics in rabbits.

Objective To investigate the expression and significance of human TREM-1 mRNA in patients with (biliary) infection. Methods Peripheral blood of 32 patients with biliary infection and 7 healthy volunteers were (collected). TREM-1 mRNA was determined by semi-quantitative RT-PCR. TNF-? was determined by ELISA method. Results The values of TREM-1/?-actin of control group was 0.48?0.072, while those of biliary infection group in 1d, 2d, 3d, 7d were 0.93?0.070,0.90?0.060,0.82?0.092,0.66?0.062 respectively (P

Objective To evaluate the influence of different clinic pathways on the time from first medical contact to balloon (FMC2B) and the time from door to balloon (D2B) for emergency patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention as well as the prognosis. Methods 183 consecutive patients were divided into emergency easy access group and normal access group. The two groups were compared in terms of the FMC2B time, D2B time and outcomes during hospitalization and follow-up. Results Compared with the normal access group, the FMC2B time in the emergency easy access group was significantly shorter (100.3 min vs. 145.6 min, P < 0.05) and so it was with the D2B time (77.1 min vs. 115.4 min, P<0.05). Meanwhile, in-hospital mortality was significantly lower (5.0%vs. 15.7%, P<0.05). The follow-ups showed the rates of re-hospitalization related to heart diseases, and the mortality rate of cardiovascular disease were significantly lower in the emergency easy access group. Conclusion The optimized emergency easy access could reduce the FMC2B time and D2B time and improve the prognosis of patients with STEMI.

Objective: To develop an HPLC method for the determination of ibrutinib in rat's plasma, and study its pharmacoki-netics. Methods: The analytical column was packed with ZORBAX XDB-C18(150 mm×4. 6 mm,5 μm). A mixture of acetonitrile-wa-ter-0. 1% trifluoroacetic acid (42 ∶ 31 ∶ 27) was used as the mobile phase with the flow rate at 1. 0 ml·min-1. The detection wave-length was set at 258 nm. The column temperature was set at 30℃. Carbamazepine was used as the internal standard. Plasma was ex-tracted under alkaline condition and ibrutinib was detected. Nine SD rats were treated with single dose of ibrutinib 15 mg·kg-1by in-tragastric administration. Blood samples were collected at different time points after ibrutinib administration. The plasma concentration of ibrutinib was detected, and the pharmacokinetic parameters were calculated by DAS software. Results: Excellent linear relationship was obtained within the range of 10 μg·L-1to 2 000 μg·L-1(r =0.999 7). The intra-day RSDs were 7.11%, 10.41% and 3. 19% , and the inter-day RSDs were 2. 56% , 1. 98% and 3. 79% respectively for three concentrations ( 25, 500 and 1 500 μg· L-1), the average recoveries were (78. 91 ± 2. 10)% , (86. 29 ± 3. 97)% and (83. 61 ± 2. 11)% , respectively. After intragastric administration of ibrutinib, the main pharmacokinetic parameters of ibrutinib were as follows:Cmaxwas(1 019.43 ±74.85)μg·L-1, Tmaxwas(4.78 ±1.20)h, AUC(0-36)was(10 417.26 ±2 167.51)μg·h·L-1, AUC(0-inf)was(10 956.72 ±2491.09)μg·h·L-1, and t1/2was(8.57 ±1.47)h. Conclusion: The method is simple, rapid and accurate, and can be applied in the studies on the phar-macokinetics of ibrutinib.

To improve the transduction efficiency of recombinant adeno-associated virus (rAAV) in NK92 cells, the number of cells, concentration of IL-2 in the medium, and serotype and dosage of rAAV were explored to optimize cell state and viral transfection conditions.Then, zinc chloride (ZnCl2), chloroquine, polyvinyl alcohol (PVA) and genistein with different concentration were added separately during transfection to further improve the viral transduction efficiency.The results showed that, at cell number of 5 × 105, the expression efficiency of enhanced green fluorescent protein (EGFP) was relatively high.When the IL-2 concentration was 1 000 IU/mL, NK92 cells were most suitable for virus transfection. The transduction efficiency of different serotypes of rAAV in NK92 cells was rAAV6, rAAV2 and rAAV9 in descending order.Pretreatment of NK92 cells with genistein could significantly increase the viral transduction efficiency, while the addition of other reagents had no significant effect.Through the optimization of the above conditions, the transduction efficiency of rAAV to NK92 cells could be significantly improved, which provided evidence for functional genetic modification of NK92 cells by rAAV.

Objective To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients'prognosis and immune infiltration.Methods TTC9A expression in different tumor tissues and its association with prognosis,DNA methylation,tumor mutation burden(TMB),and microsatellite instability(MSI)were analyzed based on data from TCGA and GTEx.TIMER and xCell were used to analyze the relationship between TTC9A expression and immune infiltration.Western blotting and RT-qPCR were used to detect the expression of TTC9A in 4 types of cancer cell lines.Results TTC9A expressions were significantly increased in many tumors and down-regulated in a few cancer types(P<0.05).Western blotting and RT-qPCR showed that TTC9A expressions were elevated in lung,colon and liver cancer cells but decreased in bladder cancer cells.In head and neck squamous cell carcinoma,renal clear cell carcinoma,renal papillary cell carcinoma,low-grade glioma,malignant mesothelioma,and endometrial carcinoma tumors,a high expression of TTC9A was strongly correlated with better overall survival(OS),disease-specific survival(DSS),and progression-free interval(PFI)(P<0.05),but was correlated with worse OS,DSS,and PFI in lung adenocarcinoma,pancreatic adenocarcinoma,adrenal carcinoma,and rectal adenocarcinoma(P<0.05).TTC9A hypermethylation was associated with a more favorable prognosis of glioblastoma multiforme,low-grade glioma,uveal melanoma,and ovarian plasmacytoid cystadenocarcinoma(P<0.05)but with poor prognosis of squamous cell carcinoma of the uterine cervix and intracervical adenocarcinoma,squamous cell carcinoma of head and neck,squamous cell carcinoma of the lungs,adrenal carcinoma,and endometrial carcinoma(P<0.05).In most of the cancer types,TTC9A was significantly correlated with the level of immune cell infiltration(P<0.05).Conclusion TTC9A can be used as a prognostic marker for a variety of cancers and is strongly associated with TBM,MSI and immune cell infiltration.

AIM: To analyze the effect of influential factors on the estimation of pharmacokinetic parameters of teicoplanin, this study was proposed to develop the population pharmacokinetic (PPK) model of teicoplanin in patients with renal insufficiency. METHODS: A total of 66 routine blood teicoplanin concentration monitoring data were collected from 46 cases with renal insufficiency, and a nonlinear mixed effect modeling program was used to establish one-compartment model with Monolix 2021R1 software. Furthermore, 20 routine blood teicoplanin concentration monitoring data were also collected from the other 20 cases with renal insufficiency, and the external validation of the model was performed by goodness-of-fit parameter method. RESULTS: The one compartment model was an appropriate model for simulating the pharmacokinetics of teicoplanin in patients with renal insufficiency. The typical values of apparent volume of distribution and clearance rate were 148.9 L and 0.13 L/h, respectively. Glomerular filtration rate and body weight, instead of other factors, were the primary variables that affected the elimination of teicoplanin in vivo. CONCLUSION: The population pharmacokinetic model of teicoplanin established in the present study was effective and stable, which could also predict the dynamic change of teicoplanin concentration. As a result, the population pharmacokinetic model could provide references for the rational use of teicoplanin in special populations.

Objective:To analyze the HIV and HBV coinfection in HIV/AIDS cases who newly received highly active antiretroviral therapy during 2005-2019 in Jiangsu province.Methods:According to the base data of HIV/AIDS cases on HAART enrolled between January 2005 and December 2019; the National Information system was retrospectively collected for HIV/AIDS Control and Prevention of Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. A Chi-square test was used to assess differences in rates of HBsAg testing and HIV/HBV coinfection between potential risk factors. The unconditional logistic regression model entered risk factors with P values <0.05 in the Chi-square test. Results:There were 29 288 HIV/AIDS cases newly received HAART during 2005-2019. The rate of HBsAg test was 49.8% (14 594/29 288) the rate of HBsAg test increased from 0.0% (0/80)to 75.2%(3 448/4 586), showing an increasing trend year by year during 2005 to 2019. Among HIV/AIDS cases tested HBsAg, 81.6% (11 915/14 594) cases were from Jiangsu province; the ratio of male to female was 7.34∶1 (12 845∶1 749), the average age was (38.5±13.8) years old, 96.1% (14 023/14 594) were Han nationality,48.9% (7 131/14 594) of the HIV/AIDS cases married, 97.9%(14 294/14 594) were infected with HIV through homosexual and heterosexual transmission. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases initiated HAART in 2015 or after that, married, not Jiangsu province resident, college education or above, and drug injection infected were more likely to have HBsAg testing. 8.6%(95% CI:8.2%-9.1%) were HBsAg positive. The HIV and HBV coinfection rates were more than 10% before 2016 while showed stability from 6.7% to 8.2% since 2016. Unconditional logistic regression modeling showed that the proportion of HIV/AIDS cases who were male, elder, married, non-Han, primary education or below were more likely to have HBV coinfection. Conclusion:More HBsAg testing should be strengthened when the HIV/AIDS cases initiated HAART in Jiangsu province, 2005-2019.

Objective:To analyze the incidence of co-infection of HIV and HBV and death in HIV/AIDS cases who newly received antiretroviral therapy (ART) from 2005-2020 in Jiangsu Province.Methods:According to the baseline and follow-up data of HIV/AIDS cases on ART enrolled between January 2005 and December 2020, the last follow-up clinical visit was up until December 31, 2022, the national information system was retrospectively collected for HIV/AIDS cases from Chinese System Disease for Control and Prevention. Excel database was established, and statistical analysis was performed using the SPSS 16.0 software. Kaplan-Meier method was used to draw the survival curves, the log rank test was used to compare the survival curves, and Cox proportional hazards modeling was used to assess the mortality and potential risk factors.Results:There were 33 322 HIV/AIDS cases that newly received ART during 2005-2020.The rate of HBsAg test was 57.3%(19 098/33 322). Among HIV/AIDS cases tested HBsAg, the ratio of male to female was 7.1∶1 (16 745∶2 353), the average age was (39.4±14.0) years old, 49.5% (9 446/19 098) of the HIV/AIDS cases were married, 57.8% (11 048/19 098) were infected with HIV through homosexual contact and 36.6% (6 990/19 098) were through heterosexual contact. The M ( Q1, Q3) of CD4 +T lymphocytes (CD4) counts at ART initiation was 297 (166, 445) cells/μl. A total of 8.2% (1 566/19 098, 95% CI:7.8%-8.6%) were HBsAg positive. There were 1 062 HIV/AIDS died by December 31, 2022. The log rank test showed that there were differences in survival curves between HIV/AIDS co-infected with HBV or not ( χ2=28.07, P<0.001). Multivariate analysis of the Cox proportional risk regression model showed that enrollment year, age, marital status, route of HIV infection, baseline CD4 counts before ART, and co-HBV infection were the influencing factors for HIV/AIDS death (all P<0.05), compared with those enrolled in 2015 and before, age ≥45 years, and those who were unmarried. Those enrolled in treatment from 2016 to 2020, those younger than 45 years, and married/cohabitation had a lower risk of death. Compared with baseline CD4 counts ≥201 cells/μl, other routes of infection, and HIV infection alone, baseline CD4 counts ≤200 cells/μl, injecting drug use, and co-HBV infection were associated with a higher risk of death. Conclusion:Effective treatment for coinfection with HBV and HBV vaccination for HBV-negative people with HIV should be integrated into HIV treatment programs to reduce HIV-related mortality in Jiangsu Province, 2005-2020.