This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Objective: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. Methods: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. Results: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. Conclusion Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

Objective:To understand the status quo of challenge-hindrance stressors in nurses of ClassⅢ general hospitals and their effects on work engagement, so as to provide guidance for nursing managers to formulate stressor coping strategies.Methods:This study was a cross-sectional survey. From October to December 2020, the convenience sampling method was used to select 1 ClassⅢ general hospital in Shanghai, Anhui Province, and Zhejiang Province, respectively. Cluster sampling was performed by department, and a total of 1 257 nurses were selected. Nurses were surveyed using general information, Challenge-Hindrance Stressor Scale (CHSS) , Recovery Experience Questionnaire (REQ) , Calling Questionnaire and Utrecht Work Engagement Scale-9 (UWES-9) . A total of 1 133 valid questionnaires were recovered, with an effective recovery rate of 90.14%.Results:The total score of challenging stressors of 1 133 nurses was (22.51±4.08) , the total score of hindrance stressors was (19.46±4.33) and the total score of UWES-9 was (42.24±10.54) . The results of path analysis showed that job mission completely mediated the relationship between challenging stressors and job engagement. Hindering stressors directly negatively predicted job engagement and recovery experience and occupational mission played a partial mediating role between them. The recovery experience had a higher mediating effect than occupational mission ( P<0.05) . Conclusions:The challenging stressors for nurses in tertiary general hospitals are at an upper-middle level and the hindrance stressors were at a moderate level. Managers should distinguish the attributes of stressors and improve work engagement of nurses according to different action paths.

Objective Toexplorethevalueofmulti-parameterquantitativeanalysisofspectralCTimaging (GSI)indifferentiatingrenal fat-poorangiomyolipoma(fpAML)andchromophobecellrenalcarcinoma(CCRC).Methods 42patientswithrenaltumor,including 25caseswithfpAMLand17caseswithCCRC,wereretrospectivelyanalyzed.Allofthem werescannedinGSImode.Themorphology differencesbetweenthefpAMLgroupandtheCCRCgroupwereanalyzed.GSIViewersoftwarewasusedtocalculatetheiodineconcentration (IC),thenormalizediodineconcentration(NIC),thesloperateofthespectrumenergycurveinthecorticalphase(CP)andmedullaryphase (MP),respectively.Thedifferencesofthoseparameterswerecomparedbetweenthetwogroupsusingthetwo-simplettest.Results Somecharacteristicsigns,suchas"blackspots"sign,cracksignandnecrosishadthevaluefordifferentialdiagnosis.IntheCP,theIC ofthefpAMLandCCRCgroupwere30.20±5.25vs19.97±4.01,theNICswere0.45±0.10vs0.32±0.06,andthesloperatesof spectrumenergycurveswere3.45±1.23vs2.42±0.48,respectively.IntheNP,theICofthefpAMLandCCRCgroupwere27.84± 8.07vs22.94±4.46,theNICswere0.58±0.17vs0.46±0.11,andthesloperatesofthespectrumenergycurveswere3.24±1.25vs 2.69±0.47,respectively.Thereweresignificantdifferencesbetween2groups(P<0.05).TheNICintheCPprovidedhighsensitivity (75%)andspecificity(86%)indifferentiatingfpAMLfrom CCRC,andtheareaundertheROCcurvewas0.886.Conclusion The focalcysticandnecrotic,enhanceduniformityanddegree,"blackspots"sign,cracksignand multi-parametersofGSI,includingIC, NIC,andthesloperateofthespectrumenergycurvecouldplayimportantroleindifferentialdiagnosisbetweenfpAMLandCCRC.

Objective: To construct an evidence-based nursing plan for stroke patients with dysphagia for nursing by searching guidelines and using Delphi method. Methods: The evidence-based nursing plan for stroke patients with dysphagia was constructed by literature review and guideline search. 15 experts from neurology, rehabilitation and nursing were selected to participate in two rounds Delphi consultation. Results: The two-round response rates were 15/15. The expert authority coefficient was 0.877. The coordination coefficients were 0.180, 0.132 and 0.185 (P<0.05). The final plan included 4 first-grade indicators, 14 second-grade indicators and 20 third-grade indicators. Conclusion The evidence-based nursing intervention plan for stroke patients with dysphagia based on Delphi method is reliable, which can provide reference for the rehabilitation nursing of stroke patients with dysphagia.

Objective To investigate the effects of salinomycin on the cell proliferation and epithelial-mesenchymal transition (EMT) of MCF-7 mammosphere (MCF-7 MS). Methods Breast cancer MCF-7 cells were cultured in suspension in serum-free medium to obtain MCF-7 MS. The cell viability of MCF-7 MS cells treated with serial concentrations of 0, 10, 30, 100, 300, 1 000, 3 000 and 10 000 nmol/L of salinomycin for 24 hours were detected by CCK-8 assay. The half maximal inhibitory concentration (IC50) was calculated. Western blot analysis was performed to detect the expression levels of E-cadherin and Snail in MCF-7 MS cells treated with 30 nmol/L and 60 nmol/L salinomycin. The same capacity of DMSO was added to MCF-7 MS as control group. The xenograft tumors from MCF-7 MS transplant mice were divided into control group (the same capacity of normal saline) and salinomycin group (5 mg/kg salinomycin), then the expressions of E-cadherin and Snail were dectected by immunohistochemical staining. Results With the increased concentration of salinomycin, the cell survival rate of MCF-7 MS cells decreased (P<0.05). The IC50 after 24 h-treatment was 989 nmol/L. Both 30 and 60 nmol/L of salinomycin increased the expression of E-cadherin and decreased the expression of Snail compared with control group. In addition, 60 nmol/L treatment group showed more significant effect (P<0.05). In xenograft tumors from MCF-7 MS transplant mice, the expression of Snail decreased, and E-cadherin increased in salinomycin treatment group compared with control group (P<0.01). Conclusion Salinomycin can inhibit the cell proliferation and EMT in MCF-7 MS cells, which is a potential drug to target cancer stem cells.

Aim To investigate the anti-proliferation effect of resveratrol (Res)on human colon cancer cells and dissect the possible mechanism underlaying this effect.Methods We introduced crystal violet staining and Western blot to analyse the anti-proliferation effect of Res on HCT1 1 6 cells.Then,we used flow cytome-try and Western blot assay to detect the Res induced apoptosis in HCT1 1 6 cells.Next,we employed the well established TCF4 /LEF luciferase reporter to meas-ure the effect of Res on Wnt/β-catenin signaling trans-duction.Finally,we took Western blot and PCR assay to analyse the effect of Res on the expression of β-cate-nin in HCT1 1 6 cells.Results Crystal violet staining and Western blot analysis showed that Res could inhib-it the proliferation of HCT1 1 6 cells in a concentration-and time dependent fashion.What’s more,Res could promote apoptosis in HCT1 1 6 cells.The transcriptional activities of TCF4 /LEF reporter were reduced by Res in a concentration-dependent fashion (P <0.05 when the concentration of Res was 20 μmol·L -1 ,and P <0.01 when the concentration of Res was 40 μmol·L -1 or 80 μmol·L -1 ).Res could decrease not only the protein level of β-catenin in HCT1 1 6 cells,but also the mRNA expression of β-catenin.Conclusion Res can inhibit the proliferation of HCT1 1 6 cells,which may be mediated at least by down-regulating the ex-pression of β-catenin to inhibit the Wnt/β-catenin sig-naling transduction.

Objective To study the association between transforming growth factor-β1 (TGF-β1) polymorphism and type 2 diabetes mellitus in Han population of Shanghai. Methods In this case-control study , 1 234 cases of T2DM patients were recruited and 1 272 healthy individuals were selected as control. Five ml of blood sample was collected from each subject ,from which the whole genomic DNA was extracted.The polymorphism was detected by the Taqman technology. Result Significant association was observed in TGF-β1 T896C genotypes and alleles with T2DM (P = 0.0001 and P = 0.004, OR = 1.18 [1.05 ~ 1.33], respectively). Conclusion The polymorphism of T896C in TGF-β1 gene may be associated with T2DM in Han population from Shanghai.

Histone deacetylases are involved in many biological processes and have roles in regulating cell behaviors such as cell cycle entry, cell proliferation and apoptosis. However, the effect of histone deacetylases on the development of hair cells (HCs) has not been fully elucidated. In this study, we examined the influence of histone deacetylases on the early development of neuromasts in the lateral line of zebrafish. Hair cell development was evaluated by fluorescent immunostaining in the absence or presence of histone deacetylase inhibitors. Our results suggested that pharmacological inhibition of histone deacetylases with inhibitors, including trichostatin A, valproic acid and MS-275, reduced the numbers of both HCs and supporting cells in neuromasts. We also found that the treatment of zebrafish larvae with inhibitors caused accumulation of histone acetylation and suppressed proliferation of neuromast cells. Real-time PCR results showed that the expression of both p21 and p27 mRNA was increased following trichostatin A treatment and the increase in p53 mRNA was modest under the same conditions. However, the expression of p53 mRNA was significantly increased by treatment with a high concentration of trichostatin A. A high concentration of trichostatin A also led to increased cell death in neuromasts as detected in a TUNEL assay. Moreover, the nuclei of most of these pyknotic cells were immunohistochemically positive for cleaved caspase-3. These results suggest that histone deacetylase activity is involved in lateral line development in the zebrafish and might have a role in neuromast formation by altering cell proliferation through the expression of cell cycle regulatory proteins.
Animals ; Apoptosis ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor Proteins/genetics/metabolism ; Histone Deacetylase Inhibitors/*pharmacology ; Histone Deacetylases/*metabolism ; Histones/metabolism ; Larva/growth & development/metabolism ; Lateral Line System/cytology/*growth & development/metabolism ; Mechanoreceptors/drug effects/*metabolism/physiology ; RNA, Messenger/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/*metabolism