BackgroundMethylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and methionine synthase reductase (MTRR) A66G polymorphisms are important genetic determinants for homocysteine (Hcy) levels, and are associated with several disorders. These polymorphisms are heterogeneously distributed worldwide. Our objective was to explore the geographical distributions of these polymorphisms in China.Methodologies15357 healthy adults were recruited from 10 regions. Buccal samples were collected and genomic DNA was isolated. Genotyping was performed using the fluorogenic 5′-nuclease assay.Principal FindingsThe prevalence of the three polymorphisms among different populations from China varied significantly and showed apparent geographical gradients. For MTHFR C677T, the frequencies of the 677T allele and the 677TT genotype were significantly higher among northern populations and ranged from the lowest values (24.0% and 6.4%, respectively) in Hainan (southern) to the highest values (63.1% and 40.8%, respectively) in Shandong (northern). For MTHFR A1298C, the 1298C allele and the 1298CC genotype frequencies were significantly higher among southern populations and increased from low values (13.1% and 1.4%, respectively) in Shandong to high values (25.7% and 6.7%, respectively) in Hainan. For A66G, the 66G allele and the 66GG genotype frequencies increased from lower values (23.7% and 5.4%, respectively) in Shandong to higher values (29.2% and 8.6%, respectively) in Hainan. The overall frequency of the 677T allele, 677TT genotype, 1298C allele, 1298CC genotype, 66G allele and 66GG genotype in the Chinese Han population was 45.2%, 23.2%, 18.6%, 3.9%, 25.7%, and 6.6%, respectively. No gender differences were found in the prevalence of both the MTHFR C677T and MTRR A66G polymorphisms.ConclusionsThis study indicates that there are marked geographical variations in the prevalence of the three polymorphisms among Chinese Han populations. Our baseline data may be useful for future researches in related fields.
Hyperhomocysteinemia (HHcy, total homocysteine concentrations > 15 μmol/L) has been associated with increased risk of many diseases. A systematic review was performed to summarize the prevalence of HHcy in China. We searched multiple international and Chinese scientific databases for relevant literature, and further manually screened reference lists and corresponded with original authors. Pooled prevalence of HHcy was calculated using random effects model. Subgroup analysis, meta-regression and sensitivity analysis were also performed. A total of 36 studies consisting 60,754 subjects (57.3% male; age range, 3–97 years) were finally included. The overall pooled prevalence of HHcy was 27.5%. Geographically, the prevalence was high in north areas, intermediate in central areas, and low in south areas, and was higher in inland versus coastal areas. The prevalence increased with age and was significantly higher in men than in women. Rural residents had a slightly higher HHcy prevalence than urban residents, and the studies conducted during 2006 to 2012 presented a higher HHcy prevalence than those during 1990 to 2005. In summary, the prevalence of HHcy in China is high, particularly in northern populations, the inlanders, males, and the elderly. Homocysteine-lowering strategies are necessary to reduce this highly preventable disorder.
The mechanisms underlying the pathogenesis of idiopathic pulmonary fibrosis (IPF) involve multiple pathways, such as inflammation, epithelial mesenchymal transition, coagulation, oxidative stress, and developmental processes. The small GTPase, RhoA, and its target protein, Rho-kinase (ROCK), may interact with other signaling pathways known to contribute to pulmonary fibrosis. This study aimed to determine the beneficial effects and mechanisms of fasudil, a selective ROCK inhibitor, on bleomycin-induced pulmonary fibrosis in mice. Our results showed that the Aschcroft score and hydroxyproline content of the bleomycin-treated mouse lung decreased in response to fasudil treatment. The number of infiltrated inflammatory cells in the bronchoalveolar lavage fluid (BALF) was attenuated by fasudil. In addition, fasudil reduced the production of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), and plasminogen activator inhibitor-1 (PAI-1) mRNA and protein expression in bleomycin-induced pulmonary fibrosis. These findings suggest that fasudil may be a potential therapeutic candidate for the treatment of pulmonary fibrosis.
Sarcoidosis is a systemic granulomatous disease, which is thought to result from an aberrant immune response. CD4+ T lymphocytes play an important role in the development of granulomas. Previously, the immunopathogenesis of sarcoidosis was focused on Th1/Th2 disturbances. The aim of this study was to evaluate the balance between newer CD4+ T lymphocytes, i.e., Treg and Th17 cells. In our studies, a decrease in Treg cells and an increase in Th17 cells were observed in the peripheral blood and BALF of sarcoidosis patients. A significant increase in the Th17/Treg cell ratio was observed in sarcoidosis patients. After treatment with prednisone, the expression of Foxp3 mRNA was elevated in the peripheral blood, and expression of (ROR)γt mRNA showed a downward trend. These findings suggest that sarcoidosis is associated with an imbalance between Th17 and Treg cells in peripheral blood and BALF. Therefore, targeting the cytokines that affect the Th17/Treg ratio could provide a new promising therapy for pulmonary sarcoidosis.
BackgroundPirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis.MethodsWe performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from literature were analyzed with Review manager 5.0.24.ResultsThe results of six randomized controlled trials (1073 participants) revealed that the number of individuals who discontinued PFD therapy was significantly higher than patients receiving placebo. The PFD group had a significantly higher rate of gastrointestinal (nausea, dyspepsia, diarrhea, and anorexia), neurological (dizziness and fatigue), and dermatological (photosensitivity and rash) AEs compared to the placebo group.ConclusionsPFD used for the treatment of pulmonary fibrosis is not so safe or well-tolerated. Notably, gastrointestinal, neurological and dermatological adverse effects were more common in patients receiving PFD therapy, and therefore appropriate precaution is needed.
Prior evidence indicates that homocysteine plays a role in the development of metabolic syndrome (MetS). Methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms are common genetic determinants of homocysteine levels. To investigate the associations of the MTHFR C677T and MTRR A66G polymorphisms with MetS, 692 Chinese Han subjects with MetS and 878 controls were recruited. The component traits of MetS and the MTHFR C677T and MTRR A66G genotypes were determined. A significant association was observed between the MTHFR 677T allele and increased risk of MetS, high fasting blood glucose, high waist circumference, and increasing number of MetS components. The MTRR A66G polymorphism was associated with an increased risk of MetS when combined with the MTHFR 677TT genotype, although there was no association found between MetS and MTRR A66G alone. Furthermore, the MTRR 66GG genotype was associated with high fasting blood glucose and triglycerides. Our data suggest that the MTHFR 677T allele may contribute to an increased risk of MetS in the northern Chinese Han population. The MTRR A66G polymorphism is not associated with MetS. However, it may exacerbate the effect of the MTHFR C677T variant alone. Further large prospective population-based studies are required to confirm our findings.
Numerous studies have investigated the distribution of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and their associations with diseases in China. In this study we conducted a systematic review and meta-analysis of these studies (715 eligible studies in total).Results revealed that the frequencies of the MTHFR C677T and A1298C polymorphisms varied markedly in different areas and ethnicities, and even showed geographical gradients. The MTHFR C677T polymorphism was significantly associated with 42 clinical disorders (p < 0.05), mostly relating to the diseases of circulatory system, birth defects and cancers. The association of the A1298C polymorphism with three diseases (coronary heart disease, breast cancer and neural tube defects fathers) was statistically significant (p < 0.05). However, according to the Venice criteria, only the associations of the C677T polymorphism with breast and ovarian cancers were assessed as having strong epidemiological credibility. This is the first study to provide a comprehensive assessment of the current status and gaps in genetic epidemiological study of the two polymorphisms in China, and its findings may be useful for medical and public health practices. Future studies are warranted to focus on the interactions of MTHFR genes with environmental exposure and with other genes, and to improve their methodological quality and reporting of findings.
Objective Pleural effusion is rarely observed in patients with multiple myeloma (MM). Myeloma cell infiltration or invasion to the pleura is very rare. This study aimed to investigate the clinical characteristics of pleural effusion in patients with MM. Methods We retrospectively reviewed the medical records of patients diagnosed with pleural effusion, MM, and pleural effusion with MM between 2004 and 2014 at Beijing Jishuitan Hospital. The present study included patients with pleural effusion who underwent cytological, bacteriological, biochemical and other testing. The cytopathology of abnormal pleural effusion cells was not diagnostic, thus flow cytometry was performed. MM was defined using the diagnosis standard of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) 2014 for MM. Results This study included 3,480 pleural effusion patients and 319 MM patients. There were 34 patients with both MM and pleural effusion (17 men and 17 women). The average age was 63 years (range, 48-84 years). Pleural effusion with MM was caused by congestive heart disease, chronic renal failure, hypoalbuminemia, pulmonary infarctions, cirrhosis, pulmonary arterial hypertension, parapneumonic effusion, tuberculous pleural effusion, and myelomatous pleural effusion (MPE). The diagnosis of MPE was confirmed by the detection of myeloma cells in the pleural fluid using flow cytometric analyses. There were only 2 MPE cases in our study. The first MPE case was a woman. The first clinical manifestation was pleural effusion, and the diagnosis was non-secretory MM, DSS stage IIIA (Durie-Salmon staging system); ISS stage I (the International Staging System). The second MPE case was a man who was diagnosed with MM IgA-κ, DSS stage IIIA; ISS stage II. Conclusion The detection rate of MPE was very low. MPE tended to present with yellow exudates and the lack of physical and chemical characteristics. Furthermore, patients with MPE exhibited many yellow nodules on the pleura. These nodules were lobulated and had abundant blood supply. The routine pleural effusion pathological examination had low sensitivity. Flow cytometry may be more useful for improving the detection rate of MPE.
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