Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Aim To investigate the effect of Rtv(a P-gp inhibitor and inducer)on the pharmacokinetics of Y101(P-gp substrate)via P-gp.Methods In short-term studies,rats received a single dose of Rtv,where-as in long-term studies they received continuous dosing for seven days.Following this treatment,Y101 was o-rally administered to analyze its blood concentration in rats.Subsequently,the mechanism by which Rtv af-fected Y101 pharmacokinetics was investigated through the everted gut sac model(in vitro),cellular uptake studies,and so on.Results Short-term administra-tion of Rtv significantly increased Y101's AUC,liver-to-plasma partition coefficient,the everted gut sac model(in vitro),and cellular accumulation.Although long-term Rtv treatment had no effect on Y101 pharma-cokinetics or hepatic distribution,it markedly reduced Y101 cellular accumulation in Caco-2 cells,concomi-tant with an upregulation of P-gp expression.Conclu-sions Short-term Rtv administration acts as a compet-itive P-gp inhibitor,enhancing Y101 intestinal absorp-tion and hepatic distribution.In contrast,the plasma pharmacokinetics and hepatic distribution of Y101 are not altered after long-term administration of Rtv,po-tentially attributable to Rtv's dual modulatory effects on P-gp involving both induction and inhibition.Hence,the potential Rtv and Y101 interaction should be close-ly monitored in the clinic.

Objective:To evaluate the feasibility of using bedside ultrasound and serum biomarkers for the prediction of sepsis-induced myocardial dysfunction(SIMD)and mortality in septic shock patients.Methods:The patients diagnosed as septic shock were enrolled in the study from January 2019 to July 2021 in PICU at Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine.Bedside ultrasound results were recorded at day 1, 2, 3, 7 and 10.Blood samples were collected at the same time, markers of myocardial injury were detected, and prognosis was recorded at 28 days.According to the left ventricular ejection fraction (LVEF), children with septic shock were divided into SIMD group and non-SIMD group.Those with LVEF <50% or decreased by ≥10% from baseline level were defined as SIMD.Differences in cardiac ultrasound parameters and biomarkers between two groups were compared.Logistic regression analysis was performed to determine the independent risk factors for SIMD and the independent risk factors for death at 28 days after septic shock.The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of different indicators in predicting SIMD and the death outcome of children with septic shock on 28 days.Results:A total of 57 children were enrolled, including 28 cases in SIMD group and 29 cases in non-SIMD group.Univariate analysis showed that there were statistically significant differences in pediatric critical illness score, N-terminal B-type natriuretic peptide(NT-proBNP), LVEF and left ventricular short axis shortening rate between two groups ( P<0.05). Logistic analysis demonstrated that LVEF( OR=0.890, 95% CI 0.818-0.969, P=0.007)and NT-proBNP ( OR=1.000, 95% CI 1.000-1.000, P=0.015)could independently predict SIMD.There were 42 cases in survival group and 15 in non-survival group according to the prognosis on 28 days.Univariate analysis showed that there were significant differences in pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I, and mitral annular plane systolic excursion(MAPSE)( P<0.05). Logistic analysis showed that only MAPSE independently predicted mortality( OR=85.670, 95% CI 1.685-4 356.736, P=0.026). Compared with MAPSE(AUC=0.727), MAPSE combined with pediatric risk mortality score Ⅲ, pediatric sequential organ failure assessment, cardiac troponin I(AUC=0.926) could be better to predict the 28 days prognosis of patients with septic shock on 28 days. Conclusion:NT-proBNP increases significantly in the early stage of SIMD.MAPSE shows no difference between SIMD and non-SIMD patients.MAPSE is correlated with the prognosis of patient with septic shock.

OBJECTIVES: To diagnose coronary artery stenosis by using the postmortem computed tomography angiography (PMCTA), and to explore the diagnostic value of PMCTA in sudden cardiac death. METHODS: Six death cases were selected, and the contrast medium iohexol was injected under high pressure through femoral artery approach with 5F pigtail catheter to obtain coronary image data and then the data was analyzed. The results of targeted coronary imaging and coronary artery calcium score (CaS) were compared with the results of conventional autopsy and histopathological examination. RESULTS: The autopsy and histopathological examination of cases with coronary artery stenosis obtained similar results in targeted coronary angiography, with a diagnostic concordance rate of 83.3%. Targeted coronary angiography could effectively show coronary artery diseases, and the CaS was consistent with the results of conventional autopsy and histopathological examination. CONCLUSIONS Targeted coronary angiography can be used as an effective auxiliary method for conventional autopsy in cases of sudden cardiac death.
Humans ; Computed Tomography Angiography/methods* ; Coronary Angiography/methods* ; Coronary Artery Disease/diagnostic imaging* ; Coronary Stenosis/diagnostic imaging* ; Death, Sudden, Cardiac/pathology*

Histiocytoma, Benign Fibrous/surgery* ; Humans ; Splenectomy ; Splenic Diseases/pathology* ; Splenic Neoplasms/surgery*

Objective To investigate the epidemiological features and antiviral response of patients with genotype 6 chronic hepatitis C (CHC) in Guangxi, China. Methods A total of 97 patients with genotype 6 CHC who were admitted to The First Affiliated Hospital of Guangxi Medical University from December 2012 to December 2020 were enrolled, among whom 62 patients were given antiviral therapy. The 62 patients receiving antiviral therapy were divided into interferon group with 22 patients and direct-acting antiviral agent (DAA) group with 40 patients. Related data were collected, including general demographic data, HCV RNA, liver function, routine blood test results, and renal function. The chi-square test was used for comparison of categorical data between groups. Results Among the 97 patients, there were 69 male patients (71.1%) and 28 female patients (28.9%), with a mean age of 41.97±10.12 years, and the patients aged 30-40 years accounted for 47.4% (46/97). Of all 97 patients, 95 (97.9%) had genotype 6a, 1 had genotype 6e, and 1 had genotype 6xa. Among the 65 patients with a definite route of infection, 41 (63.1%) had intravenous drug use, 14 had medical-related operations, 9 had blood transfusion, and 4 had sexual contact as the route of infection. For the interferon group, the rapid virologic response (RVR) rate at week 4 was 81.8% (18/22), the rate of undetectable virus at the time of drug withdrawal (Epoint) was 86.4% (19/22), the rate of sustained virologic response at 12 weeks after drug withdrawal (SVR12) was 81.8%, and the rate of sustained virological response at 24 weeks after drug withdrawal (SVR24) was 81.8%; 1 patient in this group experienced recurrence. All 40 patients in the DAA group were previously untreated patients (33 patients without liver cirrhosis and 7 patients with compensated liver cirrhosis), with an overall RVR rate of 87.5%(35/40), an Epoint rate of 100%, and an SVR12 rate of 100%, and there was no treatment failure or recurrence. Although different DAA regimens had different RVR rates, they all had a SVR12 rate of 100%. The patients with compensated liver cirrhosis and other diseases had a SVR12 rate of 100%. Conclusion Intravenous drug addiction is the main route of infection for patients with genotype 6 CHC in Guangxi, and CHC is more common in men, with genotype 6a as the main subtype. DAA treatment has a higher virologic response rate than interferon treatment, with an SVR12 rate of 100%. There is no significant difference in SVR12 rate between the patients with compensated liver cirrhosis and those without liver cirrhosis.

Quetiapine is a psychotropic drug. Excessive use of quetiapine may lead to drowsiness, blurred vision, respiratory depression, hypotension and extrapyramidal reactions. Acute respiratory distress syndrome (ARDS) is rare due to overdose of quetiapine. On 14 February 2020, a patients with coma, respiratory arrest and hypotension due to overdose of quetiapine were admitted to our hospital. After receiving mechanical ventilation、plasma adsorption and anti-inflammatory treatment, the patient's consciousness turned clear, the machine was successfully removed and extubated, and the patient's condition was improved and discharged from hospital. We analyzed the clinical data of the patient with quetiapine poisoning, and discussed the clinical symptoms and chest CT characteristics of ARDS caused by quetiapine poisoning, in order to improve the understanding of quetiapine poisoning and improve the success rate of rescue.
Antipsychotic Agents ; Dibenzothiazepines ; Drug Overdose/therapy* ; Humans ; Quetiapine Fumarate/therapeutic use* ; Respiratory Distress Syndrome