Laboratory medicine最新文献

Objective: Intellectual developmental disorder (IDD) type 5 is an autosomal dominant (AD) disorder and is characterized by intellectual disability (ID), psychomotor developmental delay, variable autism phenotypes, microcephaly, and seizure. IDD can be caused by mutations in the SYNGAP1 gene, which encodes a Ras GTPase-activating protein. This study revealed a novel de novo nonsense variant in SYNGAP1. The identification of such variants is essential for genetic counseling in patients and their families.

Methods: Exome sequencing implicated the causative variant. Sanger sequencing and cosegregation analyses were used to confirm the variant. Multiple in silico analysis tools were applied to interpret the variant using the American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.

Results: The de novo NM_006772.3(SYNGAP1):c.3685C>T variant was identified in an 11-year-old boy with severe intellectual disability, neurodevelopmental delay, speech disorder, ataxia, specific dysmorphic facial features, and aggressive behavior.

Conclusion: The current study findings expand the existing knowledge of variants in SYNGAP1 that have been previously associated with nonsyndromic intellectual disability and autism, extending the spectrum of phenotypes associated with this gene. The data have implications for genetic diagnosis and counseling in similar phenotypic presentations.

Background: Transfusion services aim to maintain sufficient blood inventory to support patients, even with challenges introduced by COVID-19.

Objectives: To review blood usage and wastage before, during, and after COVID-19 surges, and to evaluate effects on inventory.

Methods: In a retrospective review, we evaluated the association between time periods corresponding to the initial wave of COVID-19 (pre-COVID-19, quarantine, and postquarantine) and blood usage/wastage. Data were stratified by period, and χ2 testing was used to examine the association between these time periods and blood usage/wastage.

Results: In the period before COVID-19, the transfusion service used more units, and in the period after quarantine, more units went to waste. Across all time periods, the most-used product was RBCs, and the most wasted product was plasma. A statistically significant association existed between usage (χ2 [6/3209 (0.2%)]) = 24.534; P ≤.001; Cramer V = 0.62), wastage (χ2 [6/775 (0.8%)]) = 21.673; P = .001; Cramer V = 0.118), and time period. The postquarantine period displayed the highest wastage costs ($51,032.35), compared with the pre-COVID-19 period ($29,734.45).

Conclusion: Changes in blood inventory use and waste are significantly associated with the onset and continuation of COVID-19.

Objective: Nonalcoholic fatty liver disease (NAFLD), which is an emerging global chronic liver disease, has a close association with insulin resistance. We aimed to determine whether the Gly1057Asp (rs1805097) polymorphism of the insulin receptor substrate 2 (IRS2) gene is associated with NAFLD.

Methods: Using the polymerase chain reaction-restriction fragment length polymorphism method, 135 patients with biopsy-proven NAFLD and 135 controls underwent IRS2 genotype analysis.

Results: Genotype and allele distributions of the IRS2 gene Gly1057Asp variant conformed to the Hardy-Weinberg equilibrium in both the case and control groups (P > .05). The Asp/Asp genotype of IRS2 gene Gly1057Asp polymorphism compared with Gly/Gly genotype was associated with a 2.1-fold increased risk for NAFLD after adjustment for confounding factors (P = .029; odds ratio = 2.10, 95% CI = 1.23-3.97).

Conclusion: Our findings revealed for the first time that the Gly1057Asp Asp/Asp genotype of the IRS2 gene is a marker of increased NAFLD susceptibility; however, studies in other populations are required to confirm the results.

Objective: Different mitochondrial DNA genotypes can coexist in a cell population as well as in a single cell, a condition known as heteroplasmy. Here, we accurately determined the heteroplasmy levels of the m.3243A>G mutation, which is the most frequently identified mutation in patients with mitochondrial diseases, using droplet digital polymerase chain reaction (ddPCR).

Methods: The m.3243A>G heteroplasmy levels in artificial heteroplasmy controls mixed with various proportions of wild-type and mutant plasmids were measured using ddPCR, PCR-restriction fragment length polymorphism, and Sanger sequencing. The m.3243A>G heteroplasmy levels in DNA, extracted from the peripheral blood of patients with suspected mitochondrial disease and healthy subjects, were determined using ddPCR.

Results: The accuracy of the ddPCR method was high. The lower limit of detection was 0.1%, which indicated its higher sensitivity compared with other methods. The m.3243A>G heteroplasmy levels in peripheral blood, measured using ddPCR, correlated inversely with age at the time of analysis. The m.3243A>G mutation may be overlooked in the peripheral blood-derived DNA of elderly people, as patients >60 years of age have heteroplasmy levels <10%, which is difficult to detect using methods other than the highly sensitive ddPCR.

Conclusion: ddPCR may be considered an accurate and sensitive method for measuring m.3243 A>G heteroplasmy levels of mitochondrial DNA.

Objective: To investigate the association of immune response with vaccination adverse effects at peak anti-receptor-binding domain spike subunit 1 (anti-RBDS1) IgG after full vaccination with Comirnaty, Spikevax, or Vaxzevria.

Methods: Anti-RBDS1 IgG concentrations after vaccination were determined in healthy adults vaccinated with the Comirnaty, Spikevax, and Vaxzevria vaccines. The association of reactogenicity and peak antibody response after vaccination was tested.

Results: Anti-RBDS1 IgG values were significantly higher in the Comirnaty and Spikevax group, compared with the Vaxzevria group (P < .001). Fever and muscle pain were found to be significant independent predictors of peak anti-RBDS1 IgG in the Comirnaty and Spikevax groups (P = .03 and P = .02, respectively). The multivariate model, adjusted for covariates, showed that no association between reactogenicity and peak antibody concentrations was found in the Comirnaty, Spikevax, and Vaxzevria groups.

Conclusions: No association between reactogenicity and peak anti-RBDS1 IgG after vaccination with the Comirnaty, Spikevax, and Vaxzevria vaccine was found.

Objective: Metagenomic next-generation sequencing (mNGS) can be used to detect pathogens in clinical infectious diseases through the sequencing analysis of microbial and host nucleic acids in clinical samples. This study aimed to assess the diagnostic performance of mNGS in patients with infections.

Methods: In this study, 641 patients with infectious diseases were enrolled. These patients simultaneously underwent pathogen detection by both mNGS and microbial culture. Through statistical analysis, we judged the diagnostic performance of mNGS and microbial culture on different pathogens.

Results: Among 641 patients, 276 cases of bacteria and 95 cases of fungi were detected by mNGS, whereas 108 cases of bacteria and 41 cases of fungi were detected by traditional cultures. Among all mixed infections, combined bacterial and viral infections were the highest (51%, 87/169), followed by combined bacterial with fungal infections (16.57%, 28/169) and mixed bacterial, fungal, and viral infections (13.61%, 23/169). Among all sample types, bronchoalveolar lavage fluid (BALF) samples had the highest positive rate (87.8%, 144/164), followed by sputum (85.4%, 76/89) and blood samples (61.2%, 158/258). For the culture method, sputum samples had the highest positive rate (47.2%, 42/89), followed by BALF (37.2%, 61/164). The positive rate of mNGS was 69.89% (448/641), which was significantly higher than that of traditional cultures (22.31% [143/641]) (P < .05).

Conclusions: Our results show that mNGS is an effective tool for the rapid diagnosis of infectious diseases. Compared with traditional detection methods, mNGS also showed obvious advantages in mixed infections and infections with uncommon pathogens.

Objective: There are well-described impacts of biological rhythms on human physiology. With the increasing push for routine blood tests for preventative medical care and clinical and physiological research, optimizing effectiveness is paramount. This study aimed to determine whether it is feasible to assess diurnal variations of peripheral lymphocyte prevalence using finger prick blood in a small sample size.

Methods: Using polychromatic flow cytometry, the prevalence of lymphocytes was assessed using 25 µL fingertip blood samples at 8 AM and 5 PM from 8 participants.

Results: TH cells and B cells showed significantly higher percentages in the 5 PM samples, whereas NK cells demonstrated a significantly higher morning percentage. T cells, leukocytes, and cytotoxic T cells showed no significant changes.

Conclusion: The detection of diurnal variations demonstrates that small blood volumes can be used to detect lymphocyte variations. The lower blood volume required provides a new testing method for clinical and research settings.

Objective: The objective of this study was to assess oxidative stress in small for gestational age (SGA) newborns and their mothers by evaluating intra- and extracellular thiol homeostasis and the quantification of major oxidants and antioxidants.

Methods: A total of 75 mothers and their 75 newborns (43 SGA) were enrolled in this study. Thiol-disulfide homeostasis, serum myeloperoxidase, catalase, total oxidant, and antioxidant status were analyzed. Additionally, erythrocytic glutathione (GSH) homeostasis was measured.

Results: Although native and total thiol levels were decreased, disulfide levels were increased in SGA groups. Additionally, myeloperoxidase activity and total oxidant status levels were significantly elevated whereas total antioxidant status levels and enzymatic antioxidant systems were diminished in SGA groups. Similarly, intra-erythrocytic GSH homeostasis was shifted in favor of oxidants in SGA groups.

Conclusion: Our results demonstrate that insufficient antioxidant systems in mothers and a robust source of oxidative stress in SGA might contribute to the pathophysiology of SGA births.

Background: While we strive to live with SARS-CoV-2, defining the immune response that leads to recovery rather than severe disease remains highly important. COVID-19 has been associated with inflammation and a profoundly suppressed immune response.

Objective: To study myeloid-derived suppressor cells (MDSCs), which are potent immunosuppressive cells, in SARS-CoV-2 infection.

Results: Patients with severe and critical COVID-19 showed higher frequencies of neutrophilic (PMN)-MDSCs than patients with moderate illness and control individuals (P = .005). Severe disease in individuals older and younger than 60 years was associated with distinct PMN-MDSC frequencies, being predominantly higher in patients of 60 years of age and younger (P = .004). However, both age groups showed comparable inflammatory markers. In our analysis for the prediction of poor outcome during hospitalization, MDSCs were not associated with increased risk of death. Still, patients older than 60 years of age (odds ratio [OR] = 5.625; P = .02) with preexisting medical conditions (OR = 2.818; P = .003) showed more severe disease and worse outcome. Among the immunological parameters, increased C-reactive protein (OR = 1.015; P = .04) and lymphopenia (OR = 5.958; P = .04) strongly identified patients with poor prognosis.

Conclusion: PMN-MDSCs are associated with disease severity in COVID-19; however, MDSC levels do not predict increased risk of death during hospitalization.

Objective: A detection method with high efficiency and accuracy is urgently needed in clinical work. The purpose of our study was to determine the diagnostic accuracy of the Xpert MTB/RIF assay for intestinal tuberculosis (ITB).

Methods: We searched PubMed and 4 other databases from their establishment to July 19, 2022, for published essays of diagnostic performance in which Xpert MTB/RIF was used to test patients with clinically suspected ITB. An assessment of the quality of the selected literature was conducted using QUADAS-2. We built forest plots by MetaDiSc software.

Results: The pooled Xpert MTB/RIF sensitivity was 48%, and the specificity was 99%. Moreover, the positive likelihood ratio for ITB diagnosis was 21.61. The negative likelihood ratio was 0.54. There were substantial variations between the study estimates of sensitivity (I2 = 87.6%) and specificity (I2 = 82.4%).

Conclusion: Intestinal TB is detected with limited diagnostic sensitivity by Xpert MTB/RIF but with high specificity. An Xpert-positive result may facilitate the rapid identification of ITB cases. Nevertheless, a negative result has less certainty in excluding the disease.