Temporomandibular joint osteoarthritis (TMJOA) is a complex disease and has a strong genetic component in its pathogenesis. Experimental evidence suggests the involvement of biological pathway in the disease. This case-control study was designed to investigate whether five common single nucleotide polymorphisms (SNPs) in GDF5, SMAD3, RUNX2, TGFβ1 and CHST11, respectively, are associated with TMJOA in female Han Chinese patients. A total of 240 participants were evaluated comprising 114 female patients diagnosed with TMJOA based on Research Diagnostic Criteria for Temporomandibular Disorders and 126 healthy female controls. The SNPs of the five genes in the genomic DNA were examined by sequencing, and their allelic, genotypic and carriage rate frequency distributions, as well as the triple combination of the risk genotypes, were analysed using the logistic regression model. The SNP in GDF5 or SMAD3 showed significant association with TMJOA, a relatively weak association was observed in RUNX2. In the triple combinational analysis, the risk of TMJOA grew 5·09 times in the patients with five or six risk alleles (P < 0·01). This is the first study to evaluate the association of GDF5, SMAD3, RUNX2, TGFβ1 and CHST11 with TMJOA in female Han Chinese. Our study suggests that the SNPs of genes related to TGFβ family might contribute to the risk of TMJOA.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10−15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10−3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10−16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Background Candida species are commonly detected as colonizers of the oral cavity; candidiasis or candidemia can develop in patients who are immunocompromised. Use of topical or inhaled glucocorticoids can alter the spectrum of Candida species and can promote oral candidiasis. The present study aims to evaluate the diversity of Candida species in the oral cavity and their susceptibility to antifungal agents in patients undergoing treatment with systemic glucocorticoids (SGCs) compared with non-users. Methods We conducted a descriptive, analytical, cross-sectional study that enrolled 120 patients with oral problems who were undergoing treatment with SGCs and who were admitted to the hospital of the First Affiliated Hospital, College of Medicine, Zhejiang University and Zhejiang Hospital, Hangzhou, China, between February 2019 and September 2019. One hundred and twenty age-and sex-matched patients were recruited as the SGC non-user control group. Demographic data included oral complaints and underlying diseases; symptoms of oral candidiasis were identified on physical examination. Candida species were collected using a concentrated oral rinse. Identification of fungal isolates was based on conventional phenotypic methods assisted by DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. Antifungal activities of anidulafungin, amphotericin B, micafungin, caspofungin, 5-flucytosine, posaconazole, voriconazole, itraconazole, and fluconazole were evaluated using the Sensititre YeastOne TM YO10 panel supplemented by the CLSI-M27-A3 protocol. Results Fifty-two (43.33%) out of the 120 patients undergoing with SGCs were diagnosed with oral candidiasis, compared with 14 (11.67%) of the non-users ( P < 0.05). Likewise, we collected 88 strains from 73.33% of the SGC users compared with only 48 (40%) from non-users ( P < 0.05). Candida albicans was detected most frequently in both groups (45.45% vs 66.67%, respectively; P = 0.033); the overall frequency of non- Candida albicans (NCA) strains isolated from patients treated with SGCs were significantly higher than that identified among non-users (51.14% vs 33.33%, respectively; P = 0.046), although there were no significant differences concerning any single species of NCA. Resistance of C. albicans to itraconazole ( P = 0.004) and fluconazole ( P = 0.001) was significantly higher in patients treated with SGCs than in non-users; however, echinocandins, amphotericin B, voriconazole, and posaconazole were all active against strains from both participant groups with no significant differences detected. Conclusion ...

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