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Objective:To investigate the prognostic value of cardiac ultrasound left ventricular ejection fraction (LVEF) on admission in patients with septic cardiomyopathy.Methods:A retrospective cohort study was conducted. The patients with septic cardiomyopathy hospitalized in the intensive care unit of Zhoupu Hospital Affiliated to Shanghai Health College from January 2019 to March 2023 were enrolled. The general information including gender and age, LVEF on admission, severity of illness scores within 24 hours after admission [acute physiology and chronic health evaluationⅡ (APACHEⅡ) score and sequential organ failure assessment (SOFA) score], procalcitonin (PCT), cardiac biomarkers [N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT), and MB isoenzyme of creatine kinase (CK-MB)], mitochondria related indicators [aspartate aminotransferase (AST), AST/alanine aminotransferase (ALT) ratio], blood lactate (Lac), the usage of vasoactive drugs and mechanical ventilation, and the prognosis during hospitalization were collected. The differences in above clinical data between the two groups were compared. The variables with statistically significant differences in univariate analysis were incorporated into multivariate Logistic regression analysis to analyze the independent risk factors for death during hospitalization in patients with septic cardiomyopathy. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of LVEF by echocardiography on admission in patients with septic cardiomyopathy during hospitalization.Results:A total of 62 patients were enrolled, including 36 males and 26 females. Thirty-nine cases died and 23 cases survived during hospitalization, and the mortality was 62.90%. Compared with the survival group, the LVEF of patients on admission was lower in the death group [0.51 (0.40, 0.57) vs. 0.56 (0.51, 0.63), P < 0.01], APACHEⅡ score, SOFA score, Lac, NT-proBNP, CK-MB within 24 hours after admission were higher [APACHEⅡ score: 22.18±8.38 vs. 17.39±8.22, SOFA score: 9.90±3.87 vs. 7.09±3.27, Lac (mmol/L): 5.10 (2.63, 11.50) vs. 2.00 (1.40, 5.00), NT-proBNP (μg/L): 5.24 (2.84, 11.29) vs. 2.53 (0.35, 6.63), CK-MB (U/L): 1.88 (0.21, 5.33) vs. 0.17 (0.02, 1.62), all P < 0.05], and the proportion of vasoactive drug application was higher (82.05% vs. 47.83%, P < 0.01). Multivariate Logistic regression analysis showed that LVEF on admission was an independent risk factor for predicting the prognosis of patients with septic cardiomyopathy during hospitalization [odds ratio ( OR) = 0.920, 95% confidence interval (95% CI) was 0.855-0.990, P = 0.025]. ROC curve analysis showed that the area under the ROC curve (AUC) of LVEF on admission for predicting the death of patients with septic cardiomyopathy was 0.715 (95% CI was 0.585-0.845, P = 0.005). When LVEF ≤ 0.52, the sensitivity was 73.9%, and the specificity was 61.5%. Conclusions:The lower cardiac ultrasound LVEF on admission, the worse the prognosis of patients with septic cardiomyopathy. The cardiac ultrasound LVEF on admission can be used as a clinical index to evaluate the severity of the condition and predict the prognosis of patients with septic cardiomyopathy.
ABSTRACT
<p><b>OBJECTIVE</b>To study the drug sensitivity and analyze the replication kinetics of HIV-1 B and CRF07_BC subtypes with I132L or T139K/R mutations.</p><p><b>METHODS</b>The amino acids in position 132 and 139 of reverse transcriptase (RT) region of the infectious clone PNL4-3 (HIV-1 B subtype) were changed to L and T/R through site mutagenesis. Combined with the previously constructed infectious clone of HIV-1 CRF07_BC subtype with I132L and T139K/R mutations in RT region, mutated PNL4-3 infectious clones were transfected into 293T cells. The infection ability of mutated clones was detected. The drug sensitivity to NNRTIs (TMC-125, DLV, NVP, EFV) and the properties of replication kinetics were also evaluated.</p><p><b>RESULTS</b>The mutated infectious clones were constructed including PNL4-3-RT-I132L, PNL4-3-RT-T139K and PNL4-3-RT-T139R. The I132L and T139K/R mutations in HIV-1 B and CRF07_BC infectious clones reduced their drug sensitivity to NNRTIs, which accompanied with the increase of EC50 (concentration for 50% of maximal effect). In subtype CRF07_BC, I132L mutation increased EC50 by 2.55, 19.35, 28.05, 6.13 fold, T139K mutation increased EC50 by 4.67, 3.66, 7.35, 3.30 fold, and T139R mutation increased EC50 by 1.82, 4.69, 25.12, 1.89 fold, respectively. In subtype B, I132L increased EC50 by 3.91, 4.61, 6.38, 3.56 fold, T139K increased EC50 by 3.13, 1.78, 2.26, 2.10 fold, T139R increased EC50 by 5.79, 3.99, 5.78, 2.75 fold, respectively. Similar as wild type PNL4-3, the replication ability of 132L/139K/139R mutated infectious clones reached the peak in day 11. However, compared to wild type BC-WT, I132L/T139R mutations delayed the peak time to day 14 and 21.</p><p><b>CONCLUSION</b>The novel drug resistance associated mutations I132L and T139K/R can reduce the drug sensitivity to NNRTIs in subtype B and CRF07_BC, and the replication ability of CRF_07BC declined by I132L mutation.</p>
Subject(s)
Anti-HIV Agents , Drug Resistance , Genotype , HIV-1 , Kinetics , Mutation , Polymorphism, Single Nucleotide , Protein Folding , Pyridazines , Reverse Transcriptase Inhibitors , Virus ReplicationABSTRACT
<p><b>OBJECTIVE</b>To assess the association of rs13405728 polymorphism of luteinizing hormone receptor (LHR) gene with slow ovarian response during assisted reproductive technology (ART).</p><p><b>METHODS</b>Two hundred and thirty-six women were enrolled and grouped according to their genotypes. The rs13405728 polymorphism was genotyped by DNA sequencing.</p><p><b>RESULTS</b>No signifiicant difference was found in antral follicle count and anti-Mullerian hormone between the three genotypes (P>0.05). The incidence of slow response in genotype GG was lower than in the other two genotypes (P<0.05). There was no significant difference in the amount of follicle stimulating hormone required, the number of follicles ≥14 mm on human chorionic gonadotrophin day, oocytes, mature oocytes, available embryos, and the clinical pregnancy rate among the three genotypes (P>0.05). There was an independent correlation between slow ovarian response with the genotypes of rs13405728, the initial dose of gonadotropin, and the dose of luteinizing hormone required (P<0.05).</p><p><b>CONCLUSION</b>Rs13405728 of the LHR gene may be associated with slow ovarian response in ART. Various mechanisms may be involved in the poor response and slow response.</p>