[The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells].

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.

[Effect evaluation of "Smoking cessation: Doctor first"program in China].

Objective: To evaluate the effect of "Smoking cessation: Doctor first" program on smoking medical staff. Methods: From December 2016 to September 2019, 1 747 smoking medical staff from 54 units of China Tobacco Cessation Alliance were enrolled into"Smoking cessation: Doctor first"program. Demographic characteristics, smoking characteristics, degree of tobacco dependence, willingness to quit smoking and other related factors were collected during the baseline survey. Multivariate logistic regression model was used to analyze the related factors of willingness to quit. The subjects were given intensive smoking cessation intervention from October 2017 to September 2019, including education on the hazards of smoking, methods of smoking cessation and giving smoking cessation drugs. After intervention, the subjects were investigated about their smoking cessation progress and the effect of the project was evaluated. Results: The subjects were (41±11) years old, 91.9% (1 609/1 747) were male and 62.2% (1 086/1 747) were daily smokers. The main reasons for smoking included the influence of friends [697 (39.9%)], the need for social entertainment [629 (36.0%)], the relief of mental stress [589 (33.7%)] and the refreshment [459 (26.3%)]. At baseline, 52.9% (885/1 672) and 43.2% (755/1 747) smokers had intention to quit smoking and had planned to quit within one year, respectively. Multivariate logistic regression model analysis showed that: low education level [OR (95%CI) of high school and junior high school and below were 2.42 (1.61, 3.63) and 1.57 (1.18, 2.11)], daily smoking [OR (95%CI): 1.38 (1.06, 1.78)], thinking quitting smoking is not important [OR (95%CI): 4.15 (3.33, 5.18)] and having no quitting experience [OR (95%CI): 3.21 (2.53, 4.05)] were associated with no intention to quit smoking. After intensive smoking cessation intervention, 81.0% (1 415/1 747) smokers started to quit and 36.6% (518/1 415) quit smoking with drugs, both higher than the baseline level (all P values<0.001). By the end of the program, 60.2% (852/1 415) of the medical staff had quit smoking successfully. Conclusion: "Smoking cessation: Doctor first"program can improve the willingness to quit and the proportion of using smoking cessation drugs of medical staff.

[Study of the effects of long-term outcomes of autologous peripheral blood stem cell reinfusion in patients with decompensated cirrhosis].

Objective: Autologous peripheral blood stem cells (PBSC) derived from bone marrow can promote liver regeneration and improve the liver function of patients, but there are few studies on its effect on the long-term outcomes in patients with decompensated cirrhosis. Based on previous work, this study observed the clinical outcomes of PBSC treatment in patients with decompensated cirrhosis for 10 years, in order to provide more data support for the safety and efficacy of stem cells in clinical applications. Methods: Data of patients with decompensated liver cirrhosis who completed PBSC treatment in the Department of Gastroenterology of the First Affiliated Hospital of Air Force Military Medical University from August 2005 to February 2012 were included. The follow-up endpoint was death or liver transplantation, and patients who did not reach the follow-up endpoint were followed-up for at least 10 years. The patients with decompensated liver cirrhosis who met the conditions for PBSC treatment but did not receive PBSC treatment in our hospital during the same period were used as controls. Results: A total of 287 cases with decompensated liver cirrhosis had completed PBSC treatment, and 90 cases were lost to follow-up within 10 years after surgery. A total of 151 cases with complete survival follow-up data were included in the control group. There were no statistically significant differences in baseline information such as gender, age, etiological composition and liver function score between the two groups. The 10-year survival rate was higher in PBSC than control group (37.56% vs. 26.49%, P<0.05). Cholinesterase, albumin, international normalized ratio, Child-Turcotte-Pugh score, model for end-stage liver disease score, and other indicators were gradually recovered within 3 months to 1 year after PBSC treatment, and stabilized at a more desirable level in the long-term after follow-up for up to 10 years. There was no statistically significant difference in the incidence of liver cancer between the two groups (25.22% vs.31.85%, P=0.267). The age of onset of hepatocellular carcinoma was later in PBSC than control group [(56.66±7.21) years vs. (52.69±8.42) years, P<0.05]. Conclusions: This long-term observational follow-up study of more than ten years confirms that PBSC treatment can bring long-term benefits to patients with decompensated cirrhosis, with good long-term safety, thus providing more data support on the safety and efficacy of stem cells for clinical applications.

Benchmark Experiment to Prove the Role of Projectile Excited States Upon the Ion Stopping in Plasmas.

We report on a precision energy loss measurement and theoretical investigation of 100 keV/u helium ions in a hydrogen-discharge plasma. Collision processes of helium ions with protons, free electrons, and hydrogen atoms are ideally suited for benchmarking plasma stopping-power models. Energy loss results of our experiments are significantly higher than the predictions of traditional effective charge models. We obtained good agreement with our data by solving rate equations, where in addition to the ground state, also excited electronic configurations were considered for the projectile ions. Hence, we demonstrate that excited projectile states, resulting from collisions, leading to capture-, ionization-, and radiative-decay processes, play an important role in the stopping process in plasma.

MicroRNA-506-3p inhibits proliferation and promotes apoptosis in ovarian cancer cell via targeting SIRT1/AKT/FOXO3a signaling pathway.

Ovarian cancer (OC) is one of the most common tumors in females. Growing evidence shows that microRNA-506-3p (miR-506-3p) is downregulated in OC tissues. The purpose of this study was to investigate the mechanism of miR-506-3p in modulating OC. Quantitative reverse transcriptase PCR (qRT-PCR) was employed to investigate the expression of miR-506-3p and its target in OC tissues or cell lines. CCK-8 or colony formation assay was used to examine cell viability or proliferation, respectively. Flow cytometry was demonstrated to detect cell apoptosis. Western blot was then applied to analyze underlying mechanisms. The potential target of miR-506-3p was examined via luciferase reporter assay. MiR-506-3p was significantly downregulated in both human OC tissues and cell lines. Overexpression of miR-506-3p not only decreased cell viability of OC cell lines but also promoted cell apoptosis, thus inhibiting OC progression. Moreover, SIRT1 (Sirtuin 1) was found to be a direct target of miR-506-3p, and SIRT1 expression was negatively regulated by miR-506-3p in OC cell lines. Further investigation revealed that overexpression of SIRT1 could promote cell viability as well as inhibit cell apoptosis, showing the reversed effect on OC progression compared to miR-506-3p. Lastly, AKT (Protein kinase B) /FOXO3a (Forkhead box O3) signaling pathway was inactivated by miR-506-3p while activated by SIRT1, relating to regulation of miR-506-3p on OC progression. Our results revealed a novel mechanism by which miR-506-3p inhibited proliferation while promoted apoptosis of OC via inactivation of SIRT1/AKT/FOXO3a signaling pathway, suggesting that miR-506-3p might be a potential target for OC.

Micro124-mediated AHR expression regulates the inflammatory response of chronic rhinosinusitis (CRS) with nasal polyps.

MicroRNAs represent a component of the innate immune responses that can restrain inflammatory signaling, miR124 is an important member of inflammation-associated miRNAs, and abnormal miR124 expression is observed in many inflammatory diseases and immune disorders. However, the role and signaling pathways of miR124 in chronic rhinosinusitis with nasal polyps (CRSwNPs) have not been studied in detail. The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is highly conserved in evolution and plays important roles in the inflammatory response process. In our study, we describe the role of miR124 in the inflammatory response of CRS with nasal polyps. We found that the expression of miR124 was decreased in nasal polyps, and negatively correlated with the expression of AHR. MiR124 can inhibit AHR expression by directly target 3' untranslated region (3'-UTR) of AHR. To further investigate the relationship between miR124, AHR and CRS inflammatory response, we transfect HNEpC cells with miR124 mimic, miR124 inhibitors or siRNA of AHR, then all the results showed that miR124 could regulates cellular inflammatory response through negatively regulating AHR expression. This study demonstrated that the regulation of AHR expression by miR124 is critical to the development of inflammatory response in CRSwNPs.

Relationship between genetic variants of ACE2 gene and circulating levels of ACE2 and its metabolites.

WHAT IS KNOWN: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the development of essential hypertension (EH). Genetic factors remarkably influence circulating ACE2 level. OBJECTIVE: Because heritability had remarkable effects on circulating ACE2, we designed this study to shed light on whether circulating levels of ACE2, angiotensin-(1-7) and angiotensin-(1-9) were linked to single nucleotide polymorphisms (SNPs) and haplotypes in ACE2 gene. METHODS: A total of 213 patients with newly diagnosed mild to moderate EH were enrolled in the present study. Four ACE2 tag SNPs (rs2074192, rs4646171, rs4646155 and rs2106809) were genotyped, and major haplotypes consisting of these 4 SNPs were reconstructed for all subjects. Circulating levels of ACE2, angiotensin-(1-7) and angiotensin-(1-9) were measured using enzyme-linked immunosorbent assay. RESULTS: In female subjects, linear regression analysis suggested that rare alleles of ACE2 rs2074192 and rs2106809 were associated with reduced circulating angiotensin-(1-7) levels (P=.007 and P=.006, respectively). ACE2 haplotype CAGC was associated with elevated circulating angiotensin-(1-7) levels (P=.03) whereas TAGT was associated with reduced circulating angiotensin-(1-7) levels in females (P<.001). Univariate linear regression analysis revealed that circulating ACE2 levels were positively associated with systolic blood pressure (P=.02), mean arterial pressure (P=.02) and serum creatinine (P<.001) in females whereas circulating ACE2 levels were positively associated with age (P<.001) and serum creatinine (P<.001) in males. WHAT IS NEW AND CONCLUSION: ACE2 SNPs and haplotypes are associated with circulating angiotensin-(1-7) levels. ACE2 genetic variants may be the determinants of circulating angiotensin-(1-7) levels in hypertensive females.

Modeling and Simulation of A Microchannel Cooling System for Vitrification of Cells and Tissues.

BACKGROUND: The microchannel heat exchange system has several advantages and can be used to enhance heat transfer for vitrification. OBJECTIVE: To evaluate the microchannel cooling method and to analyze the effects of key parameters such as channel structure, flow rate and sample size. MATERIALS AND METHODS: A computational flow dynamics model is applied to study the two-phase flow in microchannels and its related heat transfer process. The fluid-solid coupling problem is solved with a whole field solution method (i.e., flow profile in channels and temperature distribution in the system being simulated simultaneously). RESULTS AND CONCLUSION: Simulation indicates that a cooling rate >104 C/min is easily achievable using the microchannel method with the high flow rate for a board range of sample sizes. Channel size and material used have significant impact on cooling performance. Computational flow dynamics is useful for optimizing the design and operation of the microchannel system.

[An evidence-based terlipressin therapy for gastroesophageal variceal hemorrhage].

Gastroesophageal variceal bleeding is one of the major complications of cirrhosis and also the leading causes of death in patients with decompensated cirrhosis. Terlipressin is a triglycyl-lysine vasopressin, a synthetic vasopressin analogue that is mainly used for the treatment of acute variceal hemorrhage. This article aims to review the current status of treatment of gastroesophageal variceal bleeding with terlipressin from the perspective of evidence-based medicine.

The association between GGCX, miR-133 genetic polymorphisms and warfarin stable dosage in Han Chinese patients with mechanical heart valve replacement.

WHAT IS KNOWN AND OBJECTIVE: Warfarin is a widely used anticoagulant with a narrow therapeutic index. Polymorphisms in the VKORC1, CYP2C9 and CYP4F2 genes have been verified to correlate with warfarin stable dosage (WSD). Whether any other genes or variants affect the dosage is unknown. The aim of our study was to investigate the relationship between GGCX, miR-133 variants and the WSD in Han Chinese patients with mechanical heart valve replacement (MHVR). METHODS: A total of 231 patients were enrolled in the study. Blood samples were collected for genotyping. The average WSD among subjects with different GGCX or miR-133 genotypes was compared. Regression analyses were performed to test for any association of genetic polymorphisms with WSD. RESULTS AND DISCUSSION: The warfarin dosage in patients with the GGCX rs699664 TT and rs12714145 TT genotypes was 3.77±0.93 (95% CI: 3.35-4.19) mg/d and 3.70±1.00 (95% CI: 3.32-4.09) mg/d, respectively. The GGCX rs699664 and rs12714145 genotypes were significantly associated with WSD (P<.05). But they were ruled out in the multivariate regression analysis. There were no significant differences in the average warfarin stable dosage between subjects with MIR133B rs142410335 wild-type and variant genotypes (P>.05). WHAT IS NEW AND CONCLUSION: The genotypes of GGCX rs699644 and rs12714145 were significantly associated with WSD (P<.05), but their contributions were not significant after accounting for other factors. MIR133B rs142410335 makes no significant contributions to warfarin stable dosage in Han Chinese patients with MHVR neither in univariate regression nor in multivariate regression analyses.

Macrodeformation Twins in Single-Crystal Aluminum.

Deformation twinning in pure aluminum has been considered to be a unique property of nanostructured aluminum. A lingering mystery is whether deformation twinning occurs in coarse-grained or single-crystal aluminum at scales beyond nanotwins. Here, we present the first experimental demonstration of macrodeformation twins in single-crystal aluminum formed under an ultrahigh strain rate (∼10^{6} s^{-1}) and large shear strain (200%) via dynamic equal channel angular pressing. Large-scale molecular dynamics simulations suggest that the frustration of subsonic dislocation motion leads to transonic deformation twinning. Deformation twinning is rooted in the rate dependences of dislocation motion and twinning, which are coupled, complementary processes during severe plastic deformation under ultrahigh strain rates.

MicroRNAs of the mesothorax in Qinlingacris elaeodes, an alpine grasshopper showing a wing polymorphism with unilateral wing form.

MicroRNAs (miRNAs) are now recognized as key post-transcriptional regulators in regulation of phenotypic diversity. Qinlingacris elaeodes is a species of the alpine grasshopper, which is endemic to China. Adult individuals have three wing forms: wingless, unilateral-winged and short-winged. This is an ideal species to investigate the phenotypic plasticity, development and evolution of insect wings because of its case of unilateral wing form in both the sexes. We sequenced a small RNA library prepared from mesothoraxes of the adult grasshoppers using the Illumina deep sequencing technology. Approximately 12,792,458 raw reads were generated, of which the 854,580 high-quality reads were used only for miRNA identification. In this study, we identified 49 conserved miRNAs belonging to 41 families and 69 species-specific miRNAs. Moreover, seven miRNA*s were detected both for conserved miRNAs and species-specific miRNAs, which were supported by hairpin forming precursors based on polymerase chain reaction. This is the first description of miRNAs in alpine grasshoppers. The results provide a useful resource for further studies on molecular regulation and evolution of miRNAs in grasshoppers. These findings not only enrich the miRNAs for insects but also lay the groundwork for the study of post-transcriptional regulation of wing forms.

[A three years longitudinal follow-up study of pulmonary function changes in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To investigate the characteristics and the risk factors of pulmonary function in patients with chronic obstructive pulmonary disease (COPD) for a 3 year follow-up. METHODS: Subjects diagnosed as COPD were followed up for 3 years in the Management Center of Chronic Respiratory Disease at XINQIAO Hospital from September 2009 to June 2012.This was a retrospective study. Parameters related to respiratory function mainly first second forced expiratory volume (FEV1), COPD assessment test (CAT), 6 minutes walking distance (6MWD) and acute exacerbation were recorded during follow-up. RESULTS: Although the majority of patients were treated with drugs such as inhaled corticosteroid combined with long-term bronchial dilatation during the three years, FEV1 decreased progressively. The average annual decline of FEV1 was(31.80±61.99)ml, translating into a mean annual decline of(3.74±6.18)%. However, there were significant differences in changes of FEV1. Approximately, FEV1 in 78.3% (47/60) patients decreased, only 21.7%(13/60) patients kept stable FEV1. There was a correlation between decrease of FEV1, FEV1%predicted and the exacerbation (r=0.298, 0.361, 0.273; P<0.05). Logistic regression showed that the positive bronchodilator reversibility and the initial FEV1 were the independent factors associated with significant changes in FEV1 (respectively, OR=5.54, 95%CI 1.55-19.73; OR=8.28, 95%CI 1.42-48.32). CONCLUSION: The changes of pulmonary function in patients with COPD are heterogeneous, although most patients are treated in a standard way. Nearly 80% patients still represent deterioration of pulmonary function. Decline of FEV1 is closely related to the initial pulmonary function and bronchodilator reversibility.

[A cross-sectional survey of the knowledge on chronic obstructive pulmonary disease in physicians of tertiary hospitals in Northern China].

To investigate physicians' knowledge about chronic obstructive pulmonary disease (COPD) in tertiary hospitals in northeast China. Physicians from 77 tertiary hospitals in northeast China were surveyed with a questionnaire, which included questions such as risk factors, symptoms, exacerbations, comorbidities and diagnostic criteria of COPD. Besides cigarette smoking, air pollution and pulmonary infections, only 22.5%(40/178) physicians recognized that the biomass fuels may induce COPD. Totally 59.0%(105/178) physicians recognized the importance of spirometry to the diagnosis of COPD. Besides dyspnea, cough, sputum production, wheezing and chest tightness, only 23.7%(42/177) of physicians considered that limitation of activity was an important symptom of COPD. 65.5%(116/177) physicians believed that recurrent lung infections was one of the most important comorbidities of COPD. However, less than 30%[20.9%(37/177)-28.8%(51/177)] physicians were aware of the other important comorbidities. The physicians of tertiary hospitals in northeast China need to be systematically educated on COPD to meet the new guideline.

[The multicenter study on the registration and follow-up of low anticoagulation therapy for the heart valve operation in China].

OBJECTIVE: To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations. METHODS: In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015. RESULTS: As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study. CONCLUSIONS: INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

Association between N-acetyltransferase 2 polymorphisms and pancreatic cancer risk: a meta-analysis.

N-acetyltransferase 2 (NAT2) is an essential phase II enzyme in the metabolism of aromatic and heterocyclic amines and of hydrazines. NAT2 activity can be divided into three phenotypes: rapid, intermediate, and slow. Studies identifying an association between NAT2 polymorphism and the risk of pancreatic cancer have shown conflicting results. In order to assess this relationship comprehensively, we performed a meta-analysis that involved 1607 patients with pancreatic cancer and 1682 controls from six studies, which were selected from a group of ten, identified by a search of PubMed and Embase databases up to July 2014. Relative risks (RRs) with 95% confidence intervals (CIs) were used to evaluate the relationships. In the overall analysis, no significant associations between NAT2 rapid acetylation genotypes and pancreatic cancer risk (RR = 0.93, 95%CI = 0.73-1.19) were found; however, the results showed significant heterogeneity (I2 = 55.0%). The results from subgroup analysis suggested that the rapid genotypes might decrease the risk of pancreatic cancer (RR = 0.56, 95%CI = 0.38-0.84) in Turkey, although the association was not significant in the United States population (RR = 0.97, 95%CI = 0.71-1.34) or in the multi-center studies (RR = 1.10, 95%CI = 0.90-1.34). Analysis of the slow acetylation genotypes demonstrated the converse outcomes. In conclusion, the results of our study suggested that the NAT2 slow acetylation genotypes might increase the susceptibility to pancreatic cancer in Europe but that these have no significant effects in the United States and multi-center populations.

A novel FBN1 heterozygous mutation identified in a Chinese family with autosomal dominant Marfan syndrome.

The purpose of this study was to identify the clinical features and mutations in the fibrillin-1 gene (FBN1) in a large Chinese family with autosomal dominant Marfan syndrome (MFS). Seventeen members from a Chinese family of 4 generations were included in the study. All members underwent complete ophthalmic examination. Molecular genetic analysis was performed on all subjects. All exons of FBN1 were amplified by polymerase chain reaction, sequenced, and the sequences were compared with a reference database. Variations were evaluated in family members as well as 100 normal controls. Changes in structure and function of the protein induced by amino acid variation were predicted by bioinformatic analysis. Ectopia lentis, dolichostenomelia, arachnodactyly, and tall stature were present in all patients diagnosed with MFS. The novel heterozygous missense mutation c.2243 T>G (p.C781W) in exon 19 of FBN1 was identified in all 5 patients, but not in other family members or 100 normal controls. This mutation caused an amino acid substitution of cysteine to tryptophan at position 781 (p.C781W) of the FBN1 protein. This mutation occurred in a highly conserved region and may cause structural and functional changes in the protein according to our bioinformatic analysis. Our results suggest that the novel mutation C781W of FBN1 is responsible for the pathogenesis of MFS in this pedigree.

A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.

Genetic variations within the paired box gene 6 (PAX6) gene are associated with congenital aniridia. To detect the genetic defects in a Chinese twin family with congenital aniridia and nystagmus, exons of PAX6 were amplified by polymerase chain reaction (PCR), sequenced and compared with a reference database. Six members from the family of three generations were included in the study. The twins' father presented with congenital aniridia, nystagmus and cataract at birth, while the twins presented with congenital aniridia and nystagmus. A novel mutation c.888 insA in exon 10 of PAX6 was identified in all affected individuals. This study suggests that the novel mutation c.888 insA is likely responsible for the pathogenesis of the congenital aniridia and nystagmus in this pedigree. To the best of our knowledge, this is the first report of this mutation in PAX6 gene in pedigree with aniridia. Furthermore, no PAX6 gene defect was reported in twins with congenital aniridia.

A novel NF1 frame-shift mutation (c.702_703delGT) in a Chinese family with neurofibromatosis type 1.

This study aimed to characterize the clinical features of a Chinese pedigree with neurofibromatosis type 1 (NF1) and to identify mutations in the NF1 gene. In this three-generation family containing 8 members, 5 had been diagnosed with NF1 and the others were asymptomatic. All members of the family underwent complete medical examinations. Molecular genetic analyses were performed on all subjects included in the study. All exons of NF1 were amplified by polymerase chain reaction, sequenced, and compared with a reference database. Possible changes in function of the protein induced by amino acid variants were predicted by bioinformatic analysis. In this family, the 5 patients presented different clinical phenotypes, but all manifested typical café-au-lait macules. One novel frame-shift mutation, c.702_703delGT, in exon 7 of NF1 was identified in all affected family members, but not in the unaffected family members or in 102 normal controls. This mutation generates a premature stop codon at amino acid position 720. Additionally, a synonymous mutation c.702 G>A was found in 3 family members, including 2 affected and 1 normal individuals. In conclusion, our study suggests that a novel c.702_703delGT frame-shift mutation in NF1 is likely to be responsible for the pathogenesis of NF1 in this family. To the best of our knowledge, it is the first time that a c.702_703delGT mutation has been identified in a family with neurofibromatosis type 1.