Inversed albumin-to-globulin ratio and underlying liver disease severity as a prognostic factor for survival in hepatocellular carcinoma patients undergoing transarterial chemoembolization.

PURPOSE: Previous studies have shown that an inversed albumin-to-globulin ratio (IAGR) is a predictor of the prognosis of many cancers. However, the prognostic value of an IAGR for patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) is still unclear. This study aims to evaluate the predictive value of an IAGR for the prognosis of those patients. METHODS: This study retrospectively analyzed 396 patients with HCC who received TACE. Using a cut-off value of 1.0 for the albumin-to-globulin ratio, patients were divided into a normal albumin-to-globulin ratio (NAGR) (≥1) and an IAGR (<1) group. Univariate and multivariate analyses and time-dependent receiver operating characteristic analyses were performed to identify risk factors of overall survival (OS) and cancer-specific survival (CSS). Survival nomograms were constructed based on the multivariable analysis results and further evaluated using the consistency index (C-index) and calibration curve. RESULTS: A total of 396 patients were included in the final analysis and were divided into the NAGR group (n = 298, 75.3%) and the IAGR (n = 98, 24.7%) group. The median OS and CSS were significantly worse in the IAGR group than in the NAGR group (OS: 8 vs. 26 months, CSS: 10 vs. 41 months, both P < 0.001). Multivariate analyses demonstrated that an IAGR was an independent risk factor for predicting worse OS [hazard ratio (HR), 2.024; 95% confidence interval (CI): 1.460-2.806] and CSS (HR: 2.439; 95% CI: 1.651-3.601). The nomogram-based model-related C-indexes for OS and CSS prediction were 0.715 (95% CI: 0.697-0.733) and 0.750 (95% CI: 0.729-0.771), and the calibration of the nomogram showed good consistency. CONCLUSION: The IAGR along with underlying liver disease severity were the useful prognostic predictors of OS and CSS among patients with HCC undergoing TACE and might be useful to identify high-risk patients.

Serum procalcitonin, C-reactive protein, and neutrophil gelatinase-associated lipocalin in early diagnosis of acute kidney injury after upper urinary tract calculi.

Objective: To investigate the value of serum procalcitonin(PCT), C-reactive protein(CRP), and neutrophil gelatinase-associated lipocalin(NGAL) in the early diagnosis of acute kidney injury(AKI) after upper urinary tract calculi(UUTC). Methods: The clinical data of 86 patients who underwent UUTC surgery in our hospital from March 2020 to April 2021 were analyzed retrospectively(Approval number: 20211205L, Date: 2021-12-21). Patients were divided into an AKI group (AKI≥7 days after the operation) and a Non-AKI group. PCT, CRP, and NGAL concentrations were compared before and two hours after the operation. Multivariate logistic regression analysis was used to identify risk factors affecting the early occurrence of AKI post-operation. The receiver operating characteristic curve evaluated PCT, CRP, and NGAL in the early AKI diagnosis. Results: A total of 86 patients (30 with AKI and 56 with Non-AKI) were included. Kidney injury molecule-1(KIM-1) and urinary microalbumin(mAlb) concentrations were significantly higher in the AKI group (P<0.05). PCT, CRP, and NGAL concentrations were significantly higher two hours after the operation than before the operation (P<0.05). KIM-1 levels and elevated PCT, CRP and NGAL concentrations affected the establishment of AKI after UUTC. The sensitivity of PCT, CRP, and NGAL in evaluating AKI after UUTC were 81.17%, 84.42%, and 79.02%; the specificity was 62.31%, 71.48%, and 73.32%; and the AUC was 0.812, 0.885 and 0.804 respectively. Conclusions: PCT, CRP, and NGAL concentrations in patients with AKI after UUTC were significantly increased two hours after the operation, which can be used for the early diagnosis of AKI after UUTC operation.

Mutational analysis of compound heterozygous mutation p.Q6X/p.H232R in SRD5A2 causing 46,XY disorder of sex development.

BACKGROUND: Over 100 mutations in the SRD5A2 gene have been identified in subjects with 46,XY disorder of sex development (DSD). Exploration of SRD5A2 mutations and elucidation of the molecular mechanisms behind their effects should reveal the functions of the domains of the 5α-reductase 2 enzyme and identify the cause of 46,XY DSD. Previously, we reported a novel compound heterozygous p.Q6X/p.H232R mutation of the SRD5A2 gene in a case with 46,XY DSD. Whether the compound heterozygous p.Q6X/p.H232R mutation in this gene causes 46,XY DSD requires further exploration. METHODS: The two 46,XY DSD cases were identified and sequenced. In order to identify the source of the compound heterozygous p.Q6X/p.H232R mutation, the parents, maternal grandparents, and maternal uncle were sequenced. Since p.Q6X mutation is a nonsense mutation, p.H232R mutation was transfected into HEK293 cells and dihydrotestosterone (DHT) production were analyzed by liquid chromatography-mass spectrometry (LC-MS) for 5α-reductase 2 enzyme activities test. Apparent michaelis constant (Km) were measured of p.H232R mutation to analyze the binding ability change of 5α-reductase 2 enzyme with testosterone (T) or NADPH. RESULTS: The sequence results showed that the two 46,XY DSD cases were the compound heterozygous p.Q6X/p.H232R mutation, of which the heterozygous p.Q6X mutation originating from maternal family and heterozygous p.H232R mutation originating from the paternal family. The function analysis confirmed that p.H232R variant decreased the DHT production by LC-MS test. The Km analysis demonstrated that p.H232R mutation affected the binding of SRD5A2 with T or NADPH. CONCLUSIONS: Our findings confirmed that the compound heterozygous p.Q6X/p.H232R mutation in the SRD5A2 gene is the cause of 46,XY DSD. p.H232R mutation reduced DHT production while attenuating the catalytic efficiency of the 5α-reductase 2 enzyme.