OBJECTIVE: To explore the genetic etiology for a Chinese pedigree affected with Alazami syndrome. METHODS: Genomic DNA was extracted for 2 patients and 2 unaffected members from the pedigree. Whole exome sequencing was carried out to detect potential variant in the proband, and the result was verified by Sanger sequencing. RESULTS: The proband and her sister were both found to harbor compound heterozygous variants of LARP7 gene, namely c.94A>T (p.Lys32*) and c.1141A>G (p.Lys381Glu), which were inherited from their father and mother, respectively. Both variants were predicted to be pathogenic based on bioinformatic analysis. CONCLUSION The two variants of the LARP7 gene, both were unreported previously, probably underlay the Alazami syndrome in this pedigree. Above finding has expanded the mutational spectrum of the LARP7 gene.
China ; Dwarfism ; Female ; Humans ; Intellectual Disability/genetics* ; Mutation ; Pedigree ; Ribonucleoproteins/genetics* ; Exome Sequencing

Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease. Anti-fibrosis treatment is a significant therapy for heart disease, but there is still no thorough understanding of fibrotic mechanisms. This study was carried out to ascertain the functions of cytokine receptor-like factor 1 (CRLF1) in cardiac fibrosis and clarify its regulatory mechanisms. We found that CRLF1 was expressed predominantly in cardiac fibroblasts. Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction, but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-‍β1 (TGF‍-‍β1). Gain- and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts (NMCFs) with or without TGF-‍β1 stimulation. CRLF1 overexpression increased cell viability, collagen production, cell proliferation capacity, and myofibroblast transformation of NMCFs with or without TGF‍-‍β1 stimulation, while silencing of CRLF1 had the opposite effects. An inhibitor of the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and different inhibitors of TGF-‍β1 signaling cascades, comprising mothers against decapentaplegic homolog (SMAD)‍-dependent and SMAD-independent pathways, were applied to investigate the mechanisms involved. CRLF1 exerted its functions by activating the ERK1/2 signaling pathway. Furthermore, the SMAD-dependent pathway, not the SMAD-independent pathway, was responsible for CRLF1 up-regulation in NMCFs treated with TGF-‍β1. In summary, activation of the TGF-‍β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression. CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway. CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.
Animals ; Humans ; Mice ; Disease Models, Animal ; Fibroblasts/metabolism* ; Fibrosis ; MAP Kinase Signaling System ; Mitogen-Activated Protein Kinase 3/metabolism* ; Myocardial Infarction/metabolism* ; Receptors, Cytokine/metabolism* ; Signal Transduction ; Transforming Growth Factor beta1/pharmacology*

Objective: To know condom use negotiation with clients and regular sex partners and condom use in female sex workers (FSWs), and provide reference for the development of comprehensive HIV/AIDS intervention for FSWs. Methods: The cross sectional survey was conducted in Jianshui county and Mengzi county in Honghe Hani and Yi autonomous prefecture. A total of 476 FSWs aged 16 years and above were recruited from entertainment venues, and the information about their demographic characteristics, condom use negotiation and condom use were collected by using questionnaires. Logistic regression model was used to analyze related factors of condom use after negotiation between FSWs and clients unwilling use condom. Results: A total of 852 FSWs who aged (24.29±8.44) years old participated in the survey. In past month, 499 FSWs had negotiation for condom use with unwilling clients (58.6%, 499/852), after negotiation, 441 FSWs (88.4%, 441/499) had consistent condom use in each sex with the clients. In the past one month, 99 FSWs had negotiation for unwilling use condom with regular sex partners (14.4%, 99/687), after negotiation, 54 FSWs (54.5%, 54/99) had consistent condom use in each sex with regular sex partners. Among the FSWs, 266 (53.3%, 266/499) reported that they could say "It is a mandatory requirement" to persuade clients who were unwilling to use condom. 97(19.4%, 97/499) reported that they could say "There is risk for infection" to persuade clients who were unwilling to use condoms. 115 (23.1%,115/499) reported that they could say "It is a mandatory requirement" and "there is risk for infection" to persuade their unwilling clients to use condoms. 21 (4.2%, 21/499) reported that they used other strategies. 22 (4.4%, 22/499) felt that it was difficult to persuade clients to use condoms. Multivariate logistic regression analysis showed that compared with FSWs who felt difficult in persuading clients to use condoms, FSWs who felt moderate difficulty were more likely to have consistent condom use after negotiation (OR=4.00, 95%CI: 1.55-10.32) and FSWs who felt easy in persuading clients to use condoms were also more likely to have consistent condom use (OR=30.17, 95%CI: 3.22-282.44). Compared with FSWs used other strategies to persuade their clients to use condoms, FSWs who said it was a mandatory requirement were more likely to have consistent condom use after negotiation (OR=4.44, 95%CI: 1.41-14.01) and FSWs who said it was a mandatory requirement and there was risk for infection were also more likely to have consistent condom use (OR=5.52, 95%CI: 1.55-19.73). Conclusions Negotiation for condom use increased the rate of condom use in FSWs in sex with clients who were unwilling to use condom. The negotiation strategy of "It is a mandatory requirement" would promote condom use in FSWs in sex with clients who were unwilling to use condom. Besides, the negotiation strategy of saying "there is risk for infection" had additional effects.