查看更多>>摘要：? 2021 Elsevier B.V.Background: Growth hormone is an effective therapy for growth hormone deficiency (GHD) but with a rather variable individual sensitivity. It is unclear whether rare genetic variants may contribute to the differential GH responsiveness. Methods: The present study aims to investigate the molecular etiology of GHD in Chinese children and adolescents and evaluate the impact of rare variants on therapeutic efficacies of GH. Results: Twenty-one rare heterozygous variant were classified as promising uncertain significance (n = 14), pathogenic (n = 5) or likely pathogenic (n = 2) for 21 of the 93 GHD patients. After GHD patients harboring these rare variants were excluded, inter-individual variability in the response to GH therapy obviously reduced and the negative correlation between initiation age of treatment and height SDS change became stronger in the group without rare variants. Among rare variants, 7 (likely) pathogenic variants (7.5%, 7/93) involved a total of 6 genes not only associated with GH secretion (PROKR2, LZTR1), but also growth plate chondrocyte signaling (ACAN, FBN1, COL9A1) or genetic syndromes (PTPN11). Conclusions: Rare genetic variants are an important factor contributing to differential GH responsiveness and genetic testing should be factored into accurate diagnosis and treatment decision making in the future. Clinical Trial Registration Number: ChiCTR1900026510.
查看更多>>摘要：? 2021 Elsevier B.V.Background and aims: Long-term kinetics of anti-RBD IgG and neutralizing antibodies were analyzed in a cohort of COVID-19 na?ve health care workers (HCW) undergoing SARS-CoV-2 vaccination. Methods: An anti-RBD IgG immunoassay and a surrogate virus neutralization test (sVNT) were performed at different time points up to 6 months after vaccination in 57 HCWs. Values of anti-RBD IgG predicting an high neutralizing bioactivity (>60%) were also calculated. Results: Mean (range) values of anti-RBD IgG were 294.7 (11.6–1554), 2583 (398–8391), 320.4 (42.3–1134) BAU/mL at T1 (21 days after the 1st dose [T0]), T2 (30 days after the 2nd dose) and T3 (+180 days after T0), respectively. Mean (range) percentages of neutralization (NS%) were 24 (0–76), 86 (59–96) and 82 (52–99) at T1, T2 and T3, respectively. Anti-RBD IgG values and NS% were positively correlated at T2 and T3 while anti-RBD IgG value predicting a NS% > 60 markedly differed at T2 and T3 (594 vs. 108 BAU/mL, respectively). Conclusion: While a high neutralizing bioactivity was maintained at least 6 months after vaccination in almost all individuals, the mean values of anti-RBD-IgG showed a marked decline at 6 months. The absolute value of anti-RBD IgG is a poor marker of neutralizing bioactivity.
查看更多>>摘要：? 2021 Elsevier B.V.Background: The a-secretase A disintegrin and metalloprotease-10 (ADAM-10) may have deleterious effects in acute brain injury. This study was designed to discern if a relationship between plasma ADAM-10 levels and functional outcome exists in patients with intracerebral hemorrhage (ICH). Methods: A total of 109 patients with basal ganglia hemorrhage and 100 healthy controls were included. Their plasma ADAM-10 levels were gauged. Ninety-day prognosis was assessed and poor outcome was defined as death or major disability (modified Rankin Scale score of 3 or greater). Results: Plasma ADAM-10 levels were substantially elevated in patients, as compared to controls. ADAM-10 levels were independently correlated with hematoma size and National Institutes of Health Stroke Scale (NIHSS) score. Plasma ADAM-10, NIHSS score and hematoma size emerged as the independent predictors for 90-day poor outcome. Under receiver operating characteristic curve, plasma ADAM-10 levels exhibited similar prognostic capability, as compared to hematoma size and NIHSS score; moreover, it significantly improved prognostic abilities of NIHSS and hematoma size. Conclusions: Rising plasma ADAM-10 levels are independently related to increasing severity and poor long-term functional outcome after hemorrhagic stroke, substantializing serum ADAM-10 as a useful prognostic biomarker of ICH.
查看更多>>摘要：? 2021 Elsevier B.V.Background: The relationship between serum creatinine (CR) and osteoporosis under normal renal function and the possible mediating effects mediated by physical activity (PA) are largely unknown. Methods: A total of 4,137 elderly Chinese subjects were recruited. Three models including different covariates were established. Correlation analysis and multiple linear regression analysis were used to evaluate the relationship between CR and bone mineral density (BMD) and also under different PA pattern. Logistic regression was used to investigate the interaction between CR*PA with osteoporosis. PA was used as a moderating variable to investigate the relationship between CR and BMD. Results: As we expected, the association between CR and BMD remained significant after adjusting covariates in all models. The relationship between CR and BMD showed changeable pattern in case of different physical activity. Specially, the moderating effects of PA on serum creatinine and BMD were significant for all models only in the case of medium physical activity (PA3). Conclusions: In Chinese elderly under normal renal function, serum CR is positively correlated with BMD, and medium physical activity has mediation effect on such correlation.
查看更多>>摘要：? 2021Background: The dual marker algorithm Risk of Ovarian Malignancy Algorithm (ROMA) has been widely used in the clinic for the identification of equivocal pelvic masses in ovarian carcinoma. To obtain higher diagnostic efficiency, we created a new diagnostic index, Risk of Ovarian Malignancy Index (ROMI), by combing thymidine kinase 1 (TK1), HE4 and CA125. Methods: 335 patients with pelvic masses on imaging and 46 healthy controls were enrolled. Serum TK1 was analyzed before further study. ROMI and ROMA were evaluated for diagnostic efficiency. Results: The level of TK1 was elevated in malignant ovarian tumors compared to benign masses (p < 0.001) and healthy controls (p < 0.001). TK1 expression was positively correlated with stage, intrapelvic metastasis, lymphatic metastasis and distant metastasis (all p values < 0.001). The area under the receiver operating characteristic curve (AUC) of ROMI was higher than that of ROMA for both pre- and postmenopausal women. ROMI had better sensitivity, specificity, accuracy, and positive and negative predictive values than ROMA in diagnosis of all-stage or stage I + II ovarian carcinoma for both pre- and postmenopausal women. Conclusions: TK1 is a potential biomarker in detection of ovarian carcinoma. ROMI shows better diagnostic performance than ROMA in distinguishing malignant ovarian tumors from benign masses.
查看更多>>摘要：? 2021Background and aims: The identification of underlying genes of genetic conditions has expanded greatly in the past decades, which has broadened the field of genes responsible for inherited neuromuscular diseases. We aimed to investigate mutations associated with neuromuscular disorders phenotypes in 2 Moroccan families. Material and methods: Next-generation sequencing combined with Sanger sequencing could assist with understanding the hereditary variety and underlying disease mechanisms in these disorders. Results: Two novel homozygous mutations were described in this study. The SIL1 mutation is the first identified in the Moroccan population, the mutation was identified as the main cause of Marinesco-Sjogren syndrome in one patient. While the second mutation identified in the fatty acid 2-hydroxylase gene (FA2H) was associated with the Spastic paraplegia 35 in another patient, both transmitted in an autosomal recessive pattern. Discussion and conclusions: These conditions are extremely rare in the North African population and may be underdiagnosed due to overlapping clinical characteristics and heterogeneity of these diseases. We have reported in this study mutations associated with the diseases found in the patients. In addition, we have narrowed the phenotypic spectrum, as well as the diagnostic orientation of patients with neuromuscular disorders, who might have very similar symptoms to other disease groups.
查看更多>>摘要：? 2021Background and aims: High prevalence of hypovitaminosis D is worldwide reported among pregnant women and newborns. We assessed cord blood 25-hydroxyvitamin D3 [25(OH)D3] and 3-epi-25-hydroxyvitamin D3 (C3-epimer) levels in relation to assumed maternal risk factors for hypovitaminosis D. Methods: We enrolled 246 term newborns during summer. 175/246 mothers were supplemented with a daily variable dosage (200–1,000 IU) of vitamin D3 during pregnancy. Cord blood 25(OH)D3 and C3-epimer concentrations were analyzed by high performance liquid chromatography tandem mass spectrometry. Results: Median cord blood 25(OH)D3 levels were 23.4 ng/mL (16.9–28.8). The prevalences of vitamin D sufficiency (≥ 30.0 ng/mL), insufficiency (20.0–29.9 ng/mL), and deficiency (< 20.0 ng/mL) were 19.9%, 45.9%, and 34.2%, respectively. Non-Caucasian ethnicity, housewife life, weight excess, negligible sun exposure and absent gestational vitamin D supplementation were associated with both reduced cord blood 25(OH)D3 and C3-epimer levels. C3-epimer/25(OH)D3 ratio was 15.1% (13.6%-18.4%) and it was not related to any of the assumed risk factors for hypovitaminosis D. Conclusions: Cord blood vitamin D deficiency was common, particularly in newborns from mother not receiving vitamin D supplementation and with poor sun exposure. C3-epimer levels were high in cord blood, causing possible misclassification of vitamin D status if they were not distinguished from 25(OH)D3 concentrations.
查看更多>>摘要：? 2021Background: Diverse clinical and serological manifestations of systemic lupus erythematosus (SLE) compromise its diagnosis and treatment. A more reliable biomarker for SLE, which can play a critical role in either diagnosis, monitoring the disease progress or evaluating the response to treatment for individualized therapeutic, is necessary. DNA sensor is an important mediator of inflammation in systemic autoimmune diseases. However, the potential role for DNA sensor as disease activity biomarkers for SLE remained obscure. We detected the aberrant activation of DNA sensors and the corresponding IFN-β response in SLE patients, and to evaluate their potential role as disease biomarkers for SLE. Methods: We quantified the expressions of IFN-I and DNA sensor, such as cGAS, IFI16, DDX41, DAI and their down-stream adaptor STING in PBMC derived from patients with SLE (n = 100), healthy controls (HCs) (n = 62) by real-time PCR. The relationships between the expression of cGAS or IFI16 and clinical features in SLE patients were investigated. ROC curve analysis was performed to examine the predictive value of cGAS and IFI16 in SLE diagnosis, disease activity monitoring, specific organ manifestation and therapeutic response. RNA interference-mediated depletion of IFI16 or cGAS was conducted to evaluate their impact on IFN-I response. Results: The expressions of cGAS and IFI16 were significantly higher in PBMC from SLE patients, closely correlated with the SLEDAI scores and high anti-dsDNA antibody titers. While the AUC for cGAS (0.767) was less than that of IFI16 and IFN-β, the AUC for IFI16 (0.856) and IFN-β (0.856) were similar. Expression of cGAS and IFI16 combine with IFN-β in PBMC showed high sensitivity (89.2%) and specificity (89.1%) for discrimination between mild and moderate/severe disease activity in SLE. Higher expression of IFI16 was association with ocular disorder in SLE patients. Neither IFI16 nor cGAS was a reliable indicator of therapeutic response. RNA interference-mediated depletion of IFI16 or cGAS prevented active SLE serum-induced upregulating in both IFN-α and IFN-β. Conclusions: High expression levels of cGAS and IFI16 in PBMC from SLE patients correlated strongly with disease activity. Both cGAS and IFI16 mediated signaling pathway were account for the robust production of IFN-β. Expression of cGAS and IFI16 combined with IFN-β in PBMC might serve as potential biomarkers for early diagnosis and monitoring disease activity in SLE.
查看更多>>摘要：? 2021Background: Pulmonary cryptococcosis is an opportunistic aggressive mycosis in immunocompromised patients, but it can be increasingly seen in immunocompetent patients. It is still challenging to make a rapid and accurate diagnosis due to the various clinical manifestations and limitations in the diagnostic tools. Method: A 54-year-old man presented with intermittent productive cough and fever for 1 week. A chest X-ray demonstrated multiple consolidations in both lungs. Blood biochemistry indicated elevated immunoglobulin G levels. Including sputum cultures, polymerase chain reaction (PCR) tests for severe acute respiratory syndrome coronavirus 2, influenza A and B virus were all negative. Computed tomography of the chest showed ground-glass opacities with a nodular pattern. The serum cryptococcal antigen test was positive; however, the cerebral spinal fluid was negative. The diagnosis of pulmonary cryptococcal infection was made. An initial bronchoscopy was performed unsuccessfully and the patient received intravenous fluconazole therapy for 2 weeks. Due to poor improvement of clinical condition, he then underwent a surgical lung biopsy. The pathology revealed several encapsulated yeast cells, diffuse pulmonary interstitial fibrosis, noncaseating granulomas surrounded by T lymphocytes and multinucleated giant cells with intracellular inclusions, confirming pulmonary yeast infection associated with hypersensitivity pneumonitis. Ultimately, fungal cultures of the pathology samples revealed Cryptococcus neoformans. Subsequently antifungal therapy combined with oral steroid treatment, his general condition improved. After a total of 6 months of antifungal therapy, the patient recovered completely. Conclusions: Applicable laboratory diagnosis can help facilitate the accurate and rapid diagnosis of pulmonary cryptococcosis. This report elected to provide an update on the topic of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis.
查看更多>>摘要：? 2021 Elsevier B.V.Background: Angiotensin converting enzyme (ACE) was isolated as a ‘hypertensinconverting enzyme’. There have been considerable advances in understanding the metabolic role of ACE in the body. This review attempts to highlight the role of ACE enzyme in the physiological and pathological processes occurring in the organs in which it is localized. Methods: The literature was searched from the websites of the National Library of Medicine (http://www.ncbi.nlm.nih.gov/) and Pub Med Central, the U.S. National Library of Medicine's digital archive of life sciences journal literature. Results: The involvement of ACE in regulation of blood pressure forms its central action but it has a role to play in a variety of physiological processes occurring in the organs in which it is localized like the lungs, macrophages, brain, pancreas, liver etc. It has also been implicated in the pathogenesis of a number of diseases including COVID-19. Conclusions: More studies need to be carried out in order to validate the use of ACE levels in the diagnosis and monitoring of the diseases associated, and facilitate the use of ACE inhibitors and Angiotensin Receptor Blockers in the management of the same, so this wonder molecule can be utilized to its full potential.
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