摘要
Objective To develop an ultra-performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for the simultaneous quantification of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in human plasma and to apply it to the therapeutic monitoring.Methods Dolutegravir-D5,raltegravir-D4,efavirenz-D5,lamivudine-13 C-15 N2 and tenofovir-D7 were used as internal standard,respectively.All samples were extracted using the protein precipitation method with acetonitrile and then diluted for analysis.Chromatographic separation was performed on Shim-pack XR-ODS Ⅲ(2.0 mmx50 mm,1.6 μm)column.Mobile phases A and B consisted of 0.1％formic acid in water and acetonitrile respectively.A programmed mobile phase gradient was used at a flow rate of 0.3 mL·min-1 and column temperature of 40 ℃.The tandem mass spectrometer was equipped with an electrospray ionization(ESI)source operating in multiple reaction monitoring(MRM)modes.After methodological validation,it can be used for therapeutic drug monitoring in HIV patients.Results There was good linearity in the validated concentration ranges of 62.5-3 000 ng·mL-1 for dolutegravir,10-500 ng·mL-1 for raltegravir,125-6 000 ng·mL-1for efavirenz,10-500 ng·mL-1 for lamivudine and 10-500 ng·mL-1 for tenofovir with the linear correlation coeffificients of determination(R2)of all higher than 0.998.The accuracy of both intra-day and inter-day studies ranged from 94.0％-109.3％,and the relative standard deviations were less than 7％.The IS-normalized matrix factor and extraction recoveries of all analytes were 95.7％-106.0％and 98.7％-104.5％at all concentrations.All analytes were stable in plasma at a certain storage environment.The trough blood concentrations of dolutegravir,efavirenz,lamivudine and tenofovir were 107.7-2 366.0,740.0-3 410.0,38.5-1 229.3,31.6-224.4ng·mL-1 in HIV patients,respectively.Conclusion The method is highly aceurate,easy to perform,low-cost,and suitable for therapeutic drug monitoring of dolutegravir,raltegravir,efavirenz,lamivudine and tenofovir in HIV patients.
摘要
OBJECTIVE@#To analyze the clinical manifestations of heart, liver and kidney damages in the early stage of COVID-19 to identify the indicators for these damages.@*METHODS@#We analyzed the clinical features, underlying diseases, and indicators of infection in 12 patients with COVID-19 on the second day after their admission to our hospital between January 20 and February 20, 2020.The data including CK-MB, aTnI, BNP, heart rate, changes in ECG, LVEF (%), left ventricular general longitudinal strain (GLS, measured by color Doppler ultrasound) were collected.The changes of liver function biochemical indicators were dynamically reviewed.BUN, UCR, eGFR, Ccr, and UACR and the levels of MA, A1M, IGU, and TRU were recorded.@*RESULTS@#The 12 patients included 2 severe cases, 8 common type cases, and 2 mild cases.Four of the patients presented with sinus tachycardia, ECG changes and abnormal GLS in spite of normal aTNI and LVEF; 1 patient had abnormal CKMB and BNP.On the first and third days following admission, the patients had normal ALT, AST and GGT levels.On day 7, hepatic function damage occurred in the severe cases, manifested by elevated ALT and AST levels.Abnormalities of eGFR, Ccr and UACR occurred in 8, 5 and 5 of the patients, respectively.Abnormal elevations of MA, A1M, IGU and TRU in urine protein were observed in 4, 4, 5, and 2 of the patients, respectively.@*CONCLUSIONS@#In patients with COVID-19, heart damage can be identified early by observing the GLS and new abnormalities on ECG in spite of normal aTNI and LVEF.Early liver injury is not obvious in these patients, but dynamic monitoring of the indicators of should be emplemented, especially in severe cases. In cases with normal CR and BUN, kidney damage can be detected early by calculating eGFR, Ccr and UACR and urine protein tests.
Subject(s)
Humans , Betacoronavirus , COVID-19 , Coronavirus Infections , Pandemics , Pneumonia, Viral , SARS-CoV-2摘要
Objective To explore the value of CD+4T lymphocyte count in laboratory diagnosis of AIDS complicated with pulmonary tuberculosis.Methods Forty-three patients with acute tuberculosis were selected as the subjects.Among them,14 patients had typical tuberculosis(X-ray or chest CT),29 cases were atypical tuberculosis(X-ray or chest CT).43 patients were examined by CD+4T lymphocyte count,sputum smear tuberculosis acid-fast bacilli test and T-SPOT.TB(interferon-γ release test),and the results of various methods were compared.Results The The number of CD+4T lymphocytes in patients with typical pulmonary tuberculosis was (151.26±59.47)/μL,and that in atypical pulmonary tuberculosis was (69.11±19.65)/μL,the difference was statistically significant(t=5.124,P<0.05);and with the reduction of CD+4T lymphocytes,AIDS patients showed more atypical pulmonary tuberculosis.The positive detection rates of CD+4T lymphocyte count,T-SPOT.TB and sputum smear were 86.05%,16.28% and 51.16% respectively.The positive rate of combined detection of three methods(90.70%) was significantly higher,the differences were statistically significant(x2=5.123,6.023,7.125,all P<0.05).Conclusion CD+4T lymphocyte count is of great value in the laboratory diagnosis of AIDS complicated with tuberculosis,and it is worthy to be widely carried out in clinical practice.
摘要
OBJECTIVE:To explore the effects of entecavir combined with chemotherapy on positive HBV in tumor patients with normal liver function. METHODS:106 patients were selected and divided into observation group (44 cases) and control group (62 cases) according to therapy plan. Control group received routine chemotherapy according to tumor condition;observa-tion group was given Entecavir tablets orally 0.5 mg,qd,before 1 week of chemotherapy,for consecutive 1 week. HBV reactiva-tion rate,recurrence rate of severe hepatitis,mortality rate,serum level of ALT before and after treatment and the incidence of ADR were compared between 2 groups. RESULTS:4 patients of observation group and 2 of control group withdrew from the study. HBV reactivation rate,recurrence rate of severe hepatitis and mortality were 7.5%,0,0 in observation group and 56.7%, 50.0%,13.3% in control group,with statistical significance between 2 groups(P0.05);after chemotherapy,the serum levels of ALT in 2 groups were increased significantly,and the control group was significantly higher than the observation group,with statistical significance (P0.05). CONCLUSIONS:Entecavir can effectively prevent HBV reactivation and decrease the recurrence rate of severe hepatitis and mortality rate in tumor patients dur-ing chemotherapy, and doesn’t increase the risk of ADR.
摘要
Objective To investigate the relationship between pancreatic beta cell function and liver function in hepatitis B cirrhosis with different glucose metabolism status.Methods A total of 247 patients with hepatitis B cirrhosis were included and divided into 3 groups according to measurement of fasting blood glucose (FBG),and 2h blood glucose in 75g oral glucose tolerance test(2hPG),normal glucose metabolic status group(group A,n =47),glucose tolerance impairment group(group B,n =103) and diabetes mellitus group(group C,n =97).Data of fasting and 2h postprandial blood glucose,C-peptide,insulin and glycosylated hemoglobin (HbA1c),pancreatic beta cell function index(HBCI),insulin sensitivity index (ISI),hepatitis B virus load were collected and analyzed.Results Abnormal glucose metabolism was observed in 81％ patients with hepatitis B cirrhosis,while hepatogenic diabetes accounted for 39.3％.2 hPG[(6.29 ± 3.78) mmol/L,(10.56 ± 4.26) mmol/L,(17.34 ± 5.9) mmol/L],FBG [(4.72 ±2.15)mmot/L,(5.68 ±2.81) mmol/L,(9.82 ±5.1) mmol/L],HbA1c [(4.5 ± 1.2)％ (10.56 ±4.26) ％ (9.5 ± 3.0) ％],HBV-DNA [(3.78 ± 0.52),(4.82 ± 0.61),(6.02 ± 0.63)] were compared in group A,group B and C.2hPG,FBG,HbA1c and HBV viral loads in group A were significantly lower than group B and group C (F =93.23,41.35,84.93,237.2,P ＜ 0.05).Fasting insulin [(15.65 ± 4.17) mU/L,(26.53 ± 7.22) mU/L,(30.18 ± 3.23) mU/L],postprandial insulin [(45.28 ± 10.22) mU/L,(106.8 ± 20.74) mU/L,(141.68 ±20.25) mU/L],postprandial C peptide [(5.96 ± 4.82) mU/L,(9.86 ± 5.46) mU/L,(9.54 ± 6.42) mU/L] and ISI [(-5.96 ± 0.61),(-4.92 ± 0.42),(-5.03 ± 0.51)] were compared in group C,group B and A,those values in group C were lower than group A and B,the defferences were stastistically significant (P ＜ 0.05).HBCI in three groups were (5.66 ± 0.64),(5.32 ± 1.01),(4.30 ± 1.53),respectively,the defferences were stastistically significant(F =27.55,P ＜0.05).Patients in group C with Child-Pugh C score was much more than group A and B,the defference was stastistically significant (x2 =48.6,P ＜ 0.01).Conclusion Hyperinsulinemia,increased insulin resistance and decreased insulin secretion exist in hepatitis B cirrhosis patients,and they are closely related to liver function.