ObjectivesStudies from western countries show that dentists are vulnerable to work-related musculoskeletal disorders (WMSDs) of the neck and upper extremities, but little is known about their epidemiology among members of this rapidly growing profession in China. This study aims to investigate the prevalence of WMSDs and identify potential risk factors associated with their occurrence in the dental profession in China.Setting and participantsA cross-sectional survey was carried out in 52 different hospitals in a large metropolitan city in China. A total of 304 questionnaires were distributed to respondents identified via stratified random sampling and 272 dentists (121 females and 151 males) completed the survey. The response rate was 89.5%.OutcomesVisual analogue score was used to record neck and upper limb musculoskeletal symptoms on a body chart. Work-related risk factors, including physical and psychosocial factors, were accounted for in the regression analysis.Results88% of the dentists reported at least one musculoskeletal disorder and 83.8% suffered from neck pain. In the multivariate analyses, working hours per day were associated with neck pain (OR=1.43; 95% CI 1.03 to 1.98). Inability to select the appropriate size of dental instrument was associated with shoulder (OR=2.07; 95% CI 1.00 to 4.32) and wrist/hand (OR=2.47; 95% CI 1.15 to 5.32) pain. As for psychosocial factors, high job demand was associated with symptoms in the shoulder (OR=1.09; 95% CI 1.00 to 1.18), elbow (OR=1.11; 95% CI 1.03 to 1.19) and wrist/hand (OR=1.09; 95% CI 1.02 to 1.17). Regular physical exercise was associated with decreased neck pain (OR=0.37; 95% CI 0.14 to 1.00).ConclusionsThe prevalence of WMSDs among Chinese dentists is high. Specifically, long working hours, inability to select the appropriate size of dental instrument and high job demand are the most significant risk factors.

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. In the current study, we found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, CSC-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. Furthermore, overexpression of FAM83A activated the well-characterized CSC-associated pathways transforming growth factor-β (TGF-β) signaling and Wnt/β-catenin signaling. Importantly, the FAM83A locus was amplified in a number of human cancers and silencing FAM83A in associated cancer cell lines inhibited activation of the WNT/β-catenin and TGF-β signaling pathways and reduced tumorigenicity. Taken together, these results indicate that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target.

Cisplatin has been widely employed as a cornerstone chemotherapy treatment for a wide spectrum of solid neoplasms; increasing tumor responsiveness to cisplatin has been a topic of interest for the past 30 years. Strong evidence has indicated that mitochondrial fission participates in the regulation of apoptosis in many diseases; however, whether mitochondrial fission regulates cisplatin sensitivity remains poorly understood. Here, we show that MFF mediated mitochondrial fission and apoptosis in tongue squamous cell carcinoma (TSCC) cells after cisplatin treatment and that miR-593-5p was downregulated in this process. miR-593-5p attenuated mitochondrial fission and cisplatin sensitivity by targeting the 3′ untranslated region sequence of MFF and inhibiting its translation. In exploring the underlying mechanism of miR-593-5p downregulation, we observed that BRCA1 transactivated miR-593-5p expression and attenuated cisplatin sensitivity in vitro. The BRCA1-miR-593-5p-MFF axis also affected cisplatin sensitivity in vivo. Importantly, in a retrospective analysis of multiple centers, we further found that the BRCA1-miR-593-5p-MFF axis was significantly associated with cisplatin sensitivity and the survival of patients with TSCC. Together, our data reveal a model for mitochondrial fission regulation at the transcriptional and post-transcriptional levels; we also reveal a new pathway for BRCA1 in determining cisplatin sensitivity through the mitochondrial fission program.

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