Analysis of epidemiological trends of and associated factors for tooth loss among 35- to 44-year-old adults in Guangdong, Southern China, 1995-2015: a population-based cross-sectional survey.

BACKGROUND: Tooth loss is a known marker of oral and systemic health, but large-scale population-based and cross-sectional multi-year comparative studies on tooth loss have yet to be much studied in China. This study explores the changing trends in tooth loss status and the associated factors influencing the prevalence of tooth loss over the past two decades in Guangdong, Southern China. METHODS: Data from three cross-sectional, representative oral epidemiological surveys in Guangdong Province were analyzed, including 400 in 1995, 720 in 2005, and 288 in 2015, for a total of 1408 participants. Sample selection is based on the National Census of China published by the National Bureau of Statistics. In this study, each year, the number of missing teeth (MT) and the prevalence of tooth loss (MT > 0) were calculated. Basic demographic information, socioeconomic status, caries and periodontal status, personal lifestyle factors, and dental health care behaviors were analyzed by multivariate logistic regression to estimate their associations with tooth loss. Statistical significance was evaluated with 2-sided tests with a significance level of P < 0.05. RESULTS: This study found that the mean number of missing teeth and the prevalence of tooth loss among adults aged 35-44 years in Guangdong Province did not change significantly in the first decade (1995-2005) but decreased significantly in the second decade (2005-2015) (0.94 and 40.8% in 1995, 0.99 and 42.9% in 2005, and 0.63 and 33.3% in 2015, respectively). The mean number of MT by tooth position was highest for the first and second molars, and both were larger in the mandible than in the maxilla. In 1995, populations with low educational attainment and the presence of caries or periodontal pocket (periodontal probing depth ≥ 4 mm) were associated with a higher chance of MT > 0. In 2005, those with low educational attainment, the presence of caries, and 40-44 years old were associated with a higher chance of MT > 0. Moreover, in 2015, females, rural residents, and those with caries or periodontal pocket were associated with a higher chance of MT > 0. CONCLUSIONS: Although tooth retention has improved recently (2005-2015) and the preventive effect of education level on tooth loss has increased over time, efforts to prevent tooth loss in adults need to be strengthened. Particular attention should be given to preventive interventions for women, rural residents, and those suffering from caries or periodontal pocket.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study.

PURPOSE: To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). METHODS: Patients in a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. RESULTS: Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs. T3, N0 vs. N1, and N3a vs. N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other 2 classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. CONCLUSIONS: Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

[Analysis of FBN1 gene mutations in two pedigrees affected with Marfan syndrome].

OBJECTIVE: To detect mutations of fibrillin-1 (FBN1) gene in two pedigrees affected with Marfan syndrome (MFS). WETHODS: Peripheral blood samples were collected from MFS patients and their healthy family members for extracting genomic DNA. All of the 65 exons of the FBN1 gene were analyzed by next-generation sequencing. PolyPhen-2 and SIFT was used to predict structural and functional changes in FBN1 protein. RESULTS: Patients from both pedigrees presented ocular and skeletal manifestations suggestive of MFS. Two novel heterozygous mutations of the FBN1 gene, including c.1879C>T (p.R627C) in exon 16 and c.2584T>C (p.C862R) in exon 22, were identified. The same mutations were not found among unaffected members. By bioinformatic analysis, the mutations may affect the structure and function of the FBN1 protein. CONCLUSION: The c.1879C>T and c.2584T>C mutations of the FBN1 gene probably account for the disease in the two pedigrees, respectively. Identification of the c.2584T>C has enriched the spectrum of FBN1 gene mutations.

Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis.

PURPOSE: Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and mutations in known genes can only explain 5-6% of POAG. This study was conducted to identify novel POAG-causing genes and explore the pathogenesis of this disease. METHODS: Exome sequencing was performed in a Han Chinese cohort comprising 398 sporadic cases with POAG and 2010 controls, followed by replication studies by Sanger sequencing. A heterozygous Ramp2 knockout mouse model was generated for in vivo functional study. RESULTS: Using exome sequencing analysis and replication studies, we identified pathogenic variants in receptor activity-modifying protein 2 (RAMP2) within three genetically diverse populations (Han Chinese, German, and Indian). Six heterozygous RAMP2 pathogenic variants (Glu39Asp, Glu54Lys, Phe103Ser, Asn113Lysfs*10, Glu143Lys, and Ser171Arg) were identified among 16 of 4763 POAG patients, whereas no variants were detected in any exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s aggregated in transfected cells and resulted in damage to the AM-RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 allele led to cAMP reduction and retinal ganglion cell death in mice. CONCLUSION: This study demonstrated that disruption of RAMP2/CRLR-cAMP axis could cause POAG and identified a potential therapeutic intervention for POAG.

[Association of ZP4 gene polymorphism with primary open-angle glaucoma in an ethnic Chinese population from Sichuan province].

OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNP) rs547984, rs540782, rs693421 and rs2499601 of Zona Pellucida Glycoprotein 4 (ZP4) gene with primary open-angle glaucoma (POAG) among ethnic Han Chinese from Sichuan Province. METHODS: A dye terminator-based SNaPshot method was used to genotype 336 patients with POAG and 768 healthy controls. RESULTS: No significant difference was detected in allelic frequencies of rs547984, rs540782, rs693421 and rs2499601 between the two groups (P>0.05). Haplotypic analysis showed a significant difference in G-G-A-G haplotype formed by the 4 SNPs between the POAG and the control groups (P<0.05). CONCLUSION: ZP4 gene SNPs rs547984, rs540782, rs693421, rs2499601 are not associated with POAG among ethnic Hans from Sichuan.

[Mutation analysis of FBN1 gene in a child with Marfan syndrome].

OBJECTIVE: To detect potential mutations of fibrillin-1 (FBN1) gene in a child with Marfan syndrome (MFS) and explore its molecular pathogenesis. METHODS: The 66 exons of the FBN1 gene were analyzed by direct sequencing. SIFT and PolyPhen-2 were used to predict the structural and functional changes at the protein level. RESULTS: A novel heterozygous mutation c.3998 G>A (p.Cys1333Tyr) was found in exon 32 in the child. The same mutation was not found among his unaffected family members and 683 healthy controls. Multiple sequence alignment showed that this novel mutation was located in a highly conserved region of the FBN1 protein across various species and may induce structural change to a functional domain. CONCLUSION: The novel c.3998G>A (p.Cys1333Tyr) mutation of the FBN1 gene probably predisposed the MFS in the child. Above finding has enriched the spectrum of FBN1 mutations.

A novel FBN1 mutation causes autosomal dominant Marfan syndrome.

Marfan syndrome (MFS) is an inherited and systemic disorder. It has been reported that mutations in the fibrillin­1 gene (FBN1) account for ~90% of autosomal dominant cases of MFS. This study was conducted to screen mutations of FBN1 in a Chinese family with autosomal dominant MFS; four individuals including two patients with MFS were recruited. The family members underwent complete physical, cardiovascular and ophthalmologic examinations. Genomic DNA samples were collected from the family along with 383 unrelated healthy subjects. FBN1 coding regions were amplified by polymerase chain reaction and analyzed by direct sequencing. SIFT and PolyPhen­2 were used to predict the possible structural and functional alterations of the protein. A novel heterozygous mutation c.1708 T>G (p.C570G) in exon 14 was identified, which led to a substitution of cysteine by glycine at codon 570 (p.C570G). The mutation was identified as being associated with the MFS phenotype in the affected members of this family. However, the unaffected family members and the 383 normal controls lacked the mutation. Multiple sequence alignment of the human FBN1 protein revealed that this novel mutation occurred within a highly conserved region of the FBN1 protein across different species and may induce structural alterations in this functional domain. The spectrum of MFS­associated mutations in the FBN1 gene has been enriched from this study; this may improve understanding of the molecular pathogenesis and clinical diagnosis of MFS.