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Objective: The context was designed to optimize the diagnostic utility of clinically focused exome sequencing (CFES) and shorten the diagnostic odyssey among pediatric patients suspected of monogenic disorders (MDs). Methods: Here, we retrospectively analyzed the clinical notes of 372 patients from different areas in the Jiangxi province that were referred for a diagnostic CFES and analysis from June 2018 to March 2022 with symptoms suggestive of MDs. In our study, preliminary tests using the proband-only clinical exome sequencing as a cost-effective first-tier diagnostic test for pediatric patients with unidentified MDs, supplemented by family segregation studies for targeted variants when indicated. Results: Probands with confirmed diagnostic (CD) or likely diagnostic (LD) genetic influences accounted for 12% of all cases, whereas those with an uncertain diagnosis accounted for 48%. We also found that systemic primary carnitine deficiency (CDSP) (SLC22A5 gene) and phenylketonuria (PAH gene) were relatively more prevalent, and these patients with CDSP had the most frequent c.1400C > G variant (p.S467C) and c.51C > G variant (p. F17L) in this study. In addition, statistical analysis revealed that the estimates of diagnostic yields varied across certain phenotypic features of patients, and patients with specific phenotypic traits tended to benefit more from CFES. Conclusion: The CFES may be a first-line genetic test for diagnosing young children with suspected genetic conditions, as it validates the identification of molecular genetics alterations and facilitates comprehensive medical management. Moreover, we found that infants exhibiting metabolism/homeostasis abnormalities, craniofacial /otolaryngology/ ophthalmologic abnormalities, and/or the integument were significantly more likely to receive a genetic diagnosis via CFES than infants without such features. However, due to the current study's low diagnostic yield and inherent limitations, high-quality clinical studies with larger sample sizes are still needed to provide more likely results and confirm our findings.
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Background: Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase (PAH) gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time. In China, the PAHD incidence and PAH mutation spectrum vary enormously across the provinces. A total of 5,541,627 newborns from Jiangxi province were screened by NBS between 1997 and 2021. Method: One seventy one newborns from Jiangxi province were diagnosed with PAHD. By Sanger sequencing and the multiplex ligation-dependent probe amplification (MLPA) analysis, mutation analysis was performed in 123 PAHD patients. Using an arbitrary values (AV)-based model, we compared the observed phenotype with the predicted phenotype based on the genotype. Results: In this study, we speculated the PAHD incidence of Jiangxi province was about 30.9 per 1,000,000 live births (171/5,541,627). We summarized the PAH mutation spectrum in Jiangxi province for the first time. Two novel variants (c.433G > C, c.706 + 2T > A) were found. The most prevalent variant was c.728G > A (14.1%). The overall prediction rate of the genotype-phenotype was 77.4%. Conclusion: This mutation spectrum is very meaningful to improve the diagnostic rate of PAHD and to increase the accuracy genetic counseling. This study offers data for the genotype-phenotype prediction suitable for Chinese population.
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The efficacy and safety of traditional Chinese medicine (TCM) paired with western medicine in the treatment of patients with COVID-19 remains controversial. This meta-analysis was performed to identify the effects of TCM. Seven electronic databases were reviewed from the inception of these databases to 30 June 2022. A quality assessment of the included studies was performed with the Cochrane Collaboration's tool to provide a score of high, unclear, or low risk of bias. The standard software program (Stata, version 12.0, statistical software) was used for endpoint analyses. A total of 13 RCTs involving 1398 patients conducted in China were included. The cross-sectional data from various studies were plotted, and the results illustrated that the statistically higher rates of total effectiveness (RR, 1.357; 95% CI, 1.259 to 1.464; P < 0.001), improvement of chest CT (RR, 1.249; 95% CI, 1.143 to 1.356; P < 0.001), and cough improvement (RR, 1.228; 95% CI, 1.057 to 1.570; P = 0.012) and a lower incidence of conversion to severe cases (RR, 0.408; 95% CI, 0.275 to 0.605; P < 0.001) were demonstrated in the TCM group than that of the control group. Of note, the subgroup on specific TCM of Lianhua Qingwen (LQ) revealed that the experiment group was associated with a higher rate of total effectiveness (RR, 1.248; 95% CI, 1.136 to 1.371; P < 0.001) and improvement of chest CT (RR, 1.226; 95% CI, 1.110 to 1.356; P < 0.001) and a lower rate of conversion to severe cases (RR, 0.469; 95% CI, 0.311 to 0.707; P < 0.001). However, there was no significant difference in fever improvement (RD, 0.110; 95% CI, -0.063 to 0.283; P = 0.213). The findings of this meta-analysis suggest that TCM combined with western medicine is more effective in treating COVID-19 via relieving symptoms, promoting patients' recovery, and cutting the rate of patients developing into severe conditions. However, given the relevant possible biases in our study, adequately powered and better-designed studies with long-term follow-up are required to reach a firmer conclusion.