Annals of clinical and laboratory science最新文献

Objective: Most published reports in medical literature indicate vitamin D deficiency in older adult populations, indicating the need for vitamin D supplementation. However, vitamin D is a fat soluble vitamin and some toxicity may be encountered at a level exceeding 60 ng/mL. Therefore, both vitamin D deficiency and vitamin D excess have clinical consequences.

Methods: We reviewed vitamin D status from the medical record of 528 patients aged 65 years and older where 25-hydroxy vitamin D test was ordered.

Results: Only 66 patients (12.5%) demonstrated vitamin D deficiency (25-hydroxy vitamin D concentration <20 ng/mL) while 177 patients (33.5%) showed 25-hydroxy vitamin D concentrations above 50 ng/mL, but less than 60 ng/mL. In addition, 285 patients (53.9%) showed 25-hydroxy vitamin D concentrations above the recommended upper limit of 60 ng/mL.

Conclusions: In our older adult patient population, we unexpectedly observed that most patients showed elevated 25-hydroxy vitamin D concentrations. Therefore, screening is critical to avoid excess concentration of 25-hydroxy vitamin D in elderly patients.

Objective: To analyze the clinical characteristics and genetic variations observed in fetuses with CHARGE syndrome and identify the underlying genetic causes responsible for their multisystem malformations.

Method: Amniocentesis was performed on a fetus at 21⁺⁵ weeks of gestation with multiple systemic malformations. Amniotic fluid was collected for karyotype analysis, chromosomal microarray analysis (CMA), and whole-exome sequencing (WES).

Result: The fetal karyotype and CMA results were normal; WES analysis revealed a mutation at position 61654493 on chromosome 8, specifically at the 502nd base of the gene coding sequence (c.502C>T; p.Gln168*), located in exon 2. Familial verification confirmed this as a de novo variant, as both parents exhibited wild-type alleles. In accordance with ACMG guidelines, this variant was classified as pathogenic (PVS1_VeryStrong, PS2, PS4, PM2) due to its association with multi-system abnormalities, including congenital heart defects, leading to a diagnosis of CHARGE syndrome.

Conclusions: A novel heterozygous variant in the CHD7 gene was identified, expanding the genotype-phenotype spectrum of CHD7 and providing valuable insights for genetic counseling. Mutations in the CHD7 gene may underlie multisystem malformations in fetuses. Concurrent use of CMA and WES is recommended during prenatal diagnosis to elucidate genetic causes and enhance the understanding of CHARGE syndrome.

Objective: This study was carried out with the objective of investigating the effect of baicalin (BA) on ferroptosis in acute lung injury (ALI) and elucidating BA's underlying mechanism during this process.

Methods: ALI was induced in mice with lipopolysaccharide (LPS), and BA was subsequently administered once daily for seven consecutive days. Lung injury severity was assessed via the lung wet-to-dry weight ratio (W/D ratio) calculation. Enzyme-linked immunosorbent assay (ELISA) was employed for determining inflammatory factor levels in bronchoalveolar lavage fluid (BALF). Histopathological lung tissue variations were examined through hematoxylin-eosin (HE) staining. Myeloperoxidase (MPO) activity was also evaluated in lung tissues. In vitro, ALI was simulated via the exposure of BEAS-2B to LPS for 24 h before BA treatment. The ferroptosis agonist Erastin or Sirtuin 3 (SIRT3) inhibitor 3-TYP were administered to cells for 1 h. CCK-8 assay and flow cytometry were respectively adopted for assessing cell survival and death. Ferroptosis-linked markers, like reactive oxygen species (ROS), malondialdehyde (MDA), reduced glutathione (GSH), as well as ferrous iron (Fe²⁺), were respectively quantified, along with the protein expression of glutathione peroxidase 4 (GPX4). SIRT3 protein expression was analyzed through Western blot (WB).

Results: Animal experiments showed that BA notably lowered the lung injury score (LIS), W/D ratio, MPO activity in lung tissue, and IL-1β, IL-6, and TNF-α levels in BALF (P<0.05). Moreover, BA lowered ROS, MDA, and Fe²⁺ levels in lung tissue (P<0.01), and elevated GSH content and the expression of GPX4 and SIRT3 (P<0.01). Similarly, in vitro experiments further confirmed that BA attenuated LPS-induced cellular injury and ferroptosis in BEAS-2B cells. However, Erastin and 3-TYP markedly reduced BA's ability to protect BEAS-2B cells from LPS-induced ferroptosis.

Conclusion: BA ameliorates LPS-triggered ALI through ferroptosis suppression in lung epithelial cells via the SIRT3/GPX4 pathway.

Escherichia coli (E. coli) is a versatile bacterium, presenting a wide variety of virulence factors contributing to intestinal and extraintestinal disease. This paper presents a unique case of Escherichia coli strain exhibiting an extended-spectrum beta-lactamase (ESBL) as determined by minimum inhibitory concentration (MIC), identified as sequence type 58 (ST58). The strain, isolated from a clinical specimen, displayed unusual characteristics, forming a solid subcutaneous mass and presenting a hypermucoid phenotype. Comprehensive analysis, including whole-genome sequencing (WGS) and conventional serotyping, was conducted to understand the genetic and phenotypic features of this atypical E. coli strain.

Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder marked by early-onset encephalopathy. This report investigates the genetic basis of AGS in a newborn from consanguineous parents with microcephaly, recurrent hemorrhagic strokes, brain calcifications, leukodystrophy, epilepsy, anemia, thrombocytopenia, and left ventricular hypertrophy. Next-generation sequencing-based targeted gene panel testing for epilepsy c.65-13G>A variant in the RNASEH2B gene. Both parents were identified as carriers of the heterozygous mutation, confirming autosomal recessive inheritance. RNA analysis showed that this variant created a new splice site, leading to an 11-base-pair extension in exon 2. This alteration caused a frameshift (p.Glu22Valfs*7) and subsequent truncation of the RNASEH2B protein. This case highlights the severe neurological manifestations of AGS in newborns and elucidates the pathogenic mechanism of a newly identified intronic RNASEH2B variant.

Objective: We have recently proposed hematometabolic index (HMI), defined as the product of blood hemoglobin concentration and leukocyte count after modification, as a new discriminator of cardiovascular risk. However, the relationships between HMI and the traditional cardiovascular risk factors remain to be determined.

Methods: The subjects were 10917 middle-aged men who had received annual health checkup examinations. HMI was calculated as the product of hemoglobin (g/dl)-minus-13 and leukocyte count (/μl)-minus-3000. Relationships between HMI and traditional cardiovascular risk factors were investigated.

Results: HMI tended to be lower with an increase of age and was significantly higher in smokers than in nonsmokers. HMI was significantly lower in drinkers than in nondrinkers and was significantly lower in subjects with a habit of regular exercise than in subjects without such a habit. In analysis of variance and logistic regression analysis using quartile groups of HMI, HMI was significantly associated with BMI, waist-to-height ratio, blood pressure, triglycerides, LDL cholesterol, HDL cholesterol, and hemoglobin A_1c. Adjusted odds ratios of the fourth vs. first quartiles of HMI were 3.44 (3.00~3.93) for high BMI, 3.53 (3.11~4.01) for high waist-to-height ratio, 1.54 (1.33~1.79) for hypertension, 2.56 (2.22~2.96) for high triglycerides, 1.68 (1.35~2.09) for low HDL cholesterol, 2.50 (2.15~2.91) for high LDL cholesterol, 2.15 (1.65~2.79) for diabetes, 3.89 (3.35~4.52) for high cardiometabolic index, and 3.98 (3.27~4.85) for metabolic syndrome.

Conclusion: HMI was associated with traditional cardiovascular risk factors including smoking, alcohol drinking, regular exercise, adiposity, blood pressure, blood lipids, and glycemic status. HMI declined with an increase of age. Therefore, HMI is a discriminator of cardiovascular risk that is influenced by age.

Objective: Atrial fibrillation (AF) is a common arrhythmia caused by genetic modifications affecting biological processes such as cell communication, inflammation, and ion channels. Changes that occur over time happen gradually. By understanding the functional significance of these variations, we have analyzed single nucleotide polymorphisms (SNPs) in matrix metalloproteinase 2 (MMP-2), connexin 43 (GJA1/CX43), and interleukin 6 receptor (IL-6R) in patients aged 65 or older who have been diagnosed with atrial fibrillation. This analysis is grounded in the biological processes that are related to AF.

Methods: Blood samples were collected from 301 individuals, consisting of 151 patients (77 males and 74 females) and 150 control subjects (93 males and 57 females), aged between 65 and 80. We employed a TaqMan assay, a PCR-based genotyping technique, to examine samples for the presence of three specific SNPs: rs243865 in the MMP-2 gene, rs13216675 in the GJA1/CX43 gene, and rs4845625 in the IL-6R gene.

Results: Upon comparing the patient group to the control group, a notable contrast was found in MMP-2 variations between the reference allele (C) and alternate allele (T) (p=0.0053). Individuals with the TT homozygous genotype exhibited a higher odds ratio (4.57, p=0.02).

Conclusion: A significant association has been observed between rs243865 in the MMP-2 gene, highlighting its crucial role in the pathways related to the association and development of AF. However, no significant difference was found between the control group and patients regarding the GJA1 and IL-6R genetic variations.

We report a rare case of donor-derived SF3B1-mutated myelodysplastic syndrome (MDS) arising in a 45-year-old woman following haploidentical allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia. Initial remission was achieved post-induction, and transplantation resulted in full donor chimerism. However, routine post-transplant surveillance revealed a novel SF3B1 K666N mutation, evolving to overt MDS with ring sideroblasts and multilineage dysplasia. Persistent 100% donor chimerism confirmed the donor-derived nature of the neoplasm. The patient's course was complicated by severe graft-versus-host disease, opportunistic infections, and ultimately death. This case highlights the diagnostic challenges and clinical implications of donor-derived MDS, particularly involving SF3B1 mutations, which are typically associated with favorable prognosis but remain poorly characterized in post-transplant settings.

Objective: To determine the predictive value of two neutrophil-based inflammatory indexes - the systemic inflammatory response index (SIRI) and the neutrophil-to-high density lipoprotein ratio (NHR) - in extensive-stage small cell lung cancer (ES-SCLC) patients treated with first-line immune checkpoint inhibitors (ICIs) and chemotherapy.

Methods: From May 2020 to May 2023, we enrolled 101 ES-SCLC patients receiving first-line ICIs and chemotherapy in this study. Clinicopathological features, haematological indicators including the SIRI and NHR, treatment efficacy, and patient outcome data were analyzed.

Results: There was no statistically significant difference in efficacy or outcome among enrolled patients receiving programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. The baseline SIRI (P=0.136) and NHR (P=0.453) did not perform well in predicting treatment response. The serum SIRI before treatment was not significantly different from that after two treatment cycles (P=0.113). After two treatment cycles, the serum NHR exhibited a significant decrease from its pretreatment value (P=0.004). The dynamics of the serum SIRI and NHR before therapy and at disease progression did not significantly differ (all P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) of patients were significantly longer in the high-SIRI group than in the low-SIRI group (mPFS: 7.033 vs. 5.900 months, P=0.020; mOS: 16.233 vs. 11.200 months, P=0.012). Moreover, patients in the low-NHR subgroup presented significantly longer mPFS and mOS than did those in the high-NHR subgroup (mPFS: 7.033 vs. 4.900 months, P=0.002; mOS: 13.933 vs. 8.500 months, P=0.006). Finally, multivariate analyses revealed that Eastern Cooperative Oncology Group performance status, the pretreatment serum SIRI, and the pretreatment serum NHR (all P<0.050) can serve as valuable independent predictors for PFS and OS in patients with ES-SCLC.

Conclusions: The baseline serum SIRI and NHR can serve as promising indicators of prognosis, but not treatment response, in ES-SCLC patients receiving first-line ICIs and chemotherapy.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a growing health concern with limited early treatment options. Puerarin, an active component derived from Pueraria lobata (kudzu), has been traditionally used in Chinese medicine for its potential therapeutic benefits. This study explores the effect of puerarin on the development of NAFLD and its mechanisms.

Methods: Sprague Dawley rats with NAFLD were induced with a high-fat diet (HFD). Control rats received a standard diet, while puerarin was administered by gavage (0.4 or 0.8 g/kg) daily from week 9. Body weights were recorded weekly. After 16 weeks, liver tissues and related indicators of rats were examined. Gut microbiota was assessed via 16S rRNA sequencing of fecal sample.

Results: Compared to HFD rats, those treated with puerarin showed significant reductions in body weight, liver weight, and liver index. Liver tissue levels of TG, TC, ALT, AST, and inflammatory factors were also significantly decreased. In addition, serum levels of TG, TC, and LDL-C were lower, while HDL-C level was higher in puerarin-treated groups. 16S rRNA sequencing revealed that gut microbiota composition and diversity in the puerarin groups resembled those of healthy rats, maintaining the level of Subdologranulum and decreased the level of Ruminococcus.

Conclusion: Puerarin alleviates HFD diet-induced NAFLD by reducing inflammatory cytokine production and modulating the gut microbiota. Puerarin is a potential therapeutic drug for NAFLD, and regulating the gut microbiota is an effective strategy for treating NAFLD.