Cystic fibrosis (CF) is a rare disease most commonly seen in Caucasians. Only a few Chinese CF patients have been described in literature, taking into account the large population of China. In this systematic review, we collected the clinical and genetic information of 71 Chinese CF patients based on all available data. Compared with Caucasians, Chinese CF patients often present atypical symptoms, mainly displaying symptoms of pulmonary infection with fewer digestive symptoms. An ethnicity-specific CFTR variant spectrum was also observed in CF patients of Chinese origin, with p.Gly970Asp as the most common mutation while p.Phe508del, the most common pathogenic mutation in CF patients of Caucasian origin, is rare, suggesting the necessity of a Chinese-specific CFTR variant screening panel. Besides, multiplex ligation-dependent probe amplification analysis should be routinely considered, especially for those with unidentified mutations. Potential under-diagnosis of CF in Chinese patients might be caused by a combination of atypical clinical features and genetic heterogeneity in Chinese CF patients, the inaccessibility of sweat and genetic testing facilities, and the one-child policy in China. With the approval of promising small molecule correctors and potentiators, molecular characterization of Chinese-specific CFTR mutations will help to realize more precise treatment for Chinese CF patients.

ObjectiveTo investigate the genetic contribution of ANXA11, a gene associated with amyotrophic lateral sclerosis (ALS), in Chinese ALS patients with and without cognitive dementia.MethodsSequencing all the coding exons of ANXA11 and intron-exon boundaries in 18 familial amyotrophic lateral sclerosis (FALS), 353 unrelated sporadic amyotrophic lateral sclerosis (SALS), and 12 Chinese patients with ALS-frontotemporal lobar dementia (ALS-FTD). The transcripts in peripheral blood generated from a splicing mutation were examined by reverse transcriptase PCR.ResultsWe identified 6 nonsynonymous heterozygous mutations (5 novel and 1 recurrent), 1 splice site mutation, and 1 deletion of 10 amino acids (not accounted in the mutant frequency) in 11 unrelated patients, accounting for a mutant frequency of 5.6% (1/18) in FALS, 2.3% (8/353) in SALS, and 8.3% (1/12) in ALS-FTD. The deletion of 10 amino acids was detected in 1 clinically undetermined male with an ALS family history who had atrophy in hand muscles and myotonic discharges revealed by EMG. The novel p. P36R mutation was identified in 1 FALS index, 1 patient with SALS, and 1 ALS-FTD. The splicing mutation (c.174-2A>G) caused in-frame skipping of the entire exon 6. The rest missense mutations including p.D40G, p.V128M, p.S229R, p.R302C and p.G491R were found in 6 unrelated patients with SALS.ConclusionsThe ANXA11 gene is one of the most frequently mutated genes in Chinese patients with SALS. A canonical splice site mutation leading to skipping of the entire exon 6 further supports the loss-of-function mechanism. In addition, the study findings further expand the ANXA11 phenotype, first highlighting its pathogenic role in ALS-FTD.

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BackgroundGalectin-3 and soluble suppression of tumorigenicity-2 (sST2) are promising biomarkers of cardiac fibrosis and ventricular remodeling. The purpose of this study was to investigate the diagnostic and predictive value of galectin-3 and sST2 for use in patients who have heart failure with preserved ejection fraction (HFpEF).Material/MethodsA total of 217 hospitalized patients with HF and 30 controls from a physical examination center were included. Venous blood was collected for the detection of circulating expression of galectin-3 and sST2. All the included patients were followed up regularly for 1 year (12±1 months).ResultsThe concentrations of galectin-3 and NT-proBNP were substantially higher following decreased ejection fraction (both P=0.000), except for sST2 (P=0.068 vs. control). In ROC analyses, galectin-3 and NT-proBNP distinguished HFpEF from controls with an area under the curve (AUC) of 0.819 (95% CI: 0.75–0.89, P=0.000) and 0.806 (95% CI: 0.66–0.82, P=0.000). In contrast, sST2 obtained a lower AUC of 0.584 (95% CI: 0.49–0.68, P=0.17) compared to galectni-3 and NT-proBNP. After adjustment for clinical factors and NT-proBNP, galectin-3 was strongly correlated with an increased risk of the endpoint events in HFpEF patients, and the hazard ratio per 1 SD increase of the galectin-3 level was 2.33 (95%CI: 1.72–2.94, P=0.009).ConclusionsGalectin-3 is superior to sST2 in distinguishing HFpEF from controls and HFrEF.

Objective:The aim of this study was to investigate the microRNA-200b-3p expression in lung adenocarcinoma and the possible functional associations of microRNA-200b-3p with cell proliferation, migration, and invasion.Methods:Quantitative real-time polymerase chain reaction was used to detect the expression of microRNA-200b-3p in lung adenocarcinoma samples and in the human lung adenocarcinoma cell lines A549 and H1299. A549 and H1299 cells were transfected with either a microRNA-200b-3p mimic or a negative control microRNA or either an empty vector or an adenosine triphosphate-binding cassette transporter A-1 overexpression vector. A Cell Counting Kit-8 assay was employed to assess the ability of cell proliferation. Transwell assays and transwell-Matrigel invasion assay were, respectively, utilized to assess the capacity of migration and invasion in A549 and H1299 cells.Results:The results showed that microRNA-200b-3p expression was significantly upregulated in tumor tissues compared with that in adjacent normal tissues. Overexpression of microRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis. Furthermore, adenosine triphosphate-binding cassette transporter A-1 was a direct target of microRNA-200b-3p, and this binding was verified by luciferase reporter analysis. Overexpression of adenosine triphosphate-binding cassette transporter A-1 obviously suppressed lung adenocarcinoma cell proliferation, migration, and invasion. Lung adenocarcinoma cell phenotypes induced by microRNA-200b-3p overexpression could be partially remitted by the co-overexpression of microRNA-200b-3p and adenosine triphosphate-binding cassette transporter A-1.Conclusion:This study first identified that microRNA-200b-3p is upregulated in lung adenocarcinoma cells and associated with cell proliferation and metastasis. MicroRNA-200b-3p promoted lung adenocarcinoma cell proliferation and metastasis by suppressing adenosine triphosphate-binding cassette transporter A-1. MicroRNA-200b-3p may function as a novel molecular marker and therapeutic target for lung adenocarcinoma treatment.

Background Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant disease featured by lung cysts, spontaneous pneumothorax, fibrofolliculomas and renal tumors. The causative gene for BHDS is the folliculin (FLCN) gene and more than 200 mutations have been reported in FLCN, mostly truncating mutations. The aim of this study is to better characterize the clinical features and mutation spectrum of Chinese BHDS patients and to systematically evaluate the effects of non-truncating mutations on mRNA splicing pattern. Methods We enrolled 47 patients from 39 unrelated families with symptoms highly suggestive of BHDS after informed consent and detailed clinical data were collected. Exon sequencing followed by multiplex ligation-dependent probe amplification testing were applied for mutation screening. The effects of non-truncating mutations, including 15 missense mutations and 6 in-frame deletions, on mRNA splicing were investigated by minigene assays. Results A total of 24 FLCN germline variants were found in 39 patients from 31 distinct families. Out of these patients, 100% (36/36) presented with lung cysts and 58.3% (21/36) had experienced spontaneous pneumothorax. Seventeen mutation carriers had skin lesions (47.2%, 17/36) and 9 (30%, 9/30) had kidney lesions including 8 with renal cysts and 1 with renal hamartoma. Among all detected variants 14 (58.3%, 14/24) were novel, including 11 variants classified to be pathogenic and 3 variants of uncertain significance. None of 21 non-truncating mutations changed the mRNA splicing pattern of minigenes. Conclusions We found different clinical features of Chinese BHDS patients compared with Caucasians, with more lung cysts and pneumothorax but fewer skin lesions and malignant renal cancer. Chinese patients with BHDS also have a different mutation spectrum from other races. Non-truncating mutations in FLCN did not disrupt mRNA splicing pattern, in turn supporting the hypothesis that these mutations impair folliculin function by disrupting the stability of the FLCN gene product.

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BackgroundGrowth differentiation factor-15 (GDF-15) is a promising biomarker of cardiac remodeling. The purpose of this study was to explore the diagnostic value of plasma GDF-15 levels in different stages of heart failure (HF) and to assess the relationship with ventricular remodeling.Material/MethodsWe enrolled 219 HF patients from the Department of Cardiology in Tianjin Union Medical Center as the HF group and 32 healthy subjects as the control group. Circulating GDF-15, NT-proBNP, procollagen I C-terminal propeptide (PICP), and N-terminal procollagen III propeptide (PIIINP) levels were measured using ELISA. Associations between GDF-15 and clinical indicators in cardiac remodeling were assessed using receiver operating characteristic (ROC) curves and Spearman correlation. All the patients were followed up for 1 year.ResultsThe level of plasma GDF-15 in HF patients was higher than in the control group (P<0.05) and increased with higher ACCF/AHA and NYHA classification (P<0.05). Patients with HFrEF had higher GDF-15 levels compared to patients with HFmrEF (P<0.05). GDF-15 and left ventricular mass index (LVMI) were significantly increased as early as the pre-clinical HF stage. Also, GDF-15 levels were positively correlated to LVMI (r=0.433, P<0.05), PICP (r=0.378, P<0.001) and PIIINP (r=0.382, P<0.001). ROC curves were constructed and GDF-15 plus NT-proBNP (AUC=0.905, 95%CI: 0.868–0.942, P<0.001) was superior to NT-proBNP (AUC=0.869, 95%CI: 0.825–0.913, P<0.001) in identifying HF. GDF-15 levels did not predict prognosis after a 1-year follow-up period.ConclusionsGDF-15 combined with NT-proBNP significantly improves the accuracy of diagnosing HF. Plasma GDF-15 levels can indirectly reflect the degree of cardiac remodeling and fibrosis.