Naringenin (4,5,7-trihydroxyflavonoid) is a naturally occurring bioflavonoid found in citrus fruits, which plays an important role in metabolic syndrome, neurological disorders, and cardiovascular diseases. However, the pharmacological mechanism and biological function of naringenin on anti-angiogenesis and anti-tumor immunity have not yet been elucidated. Our study firstly demonstrates that naringenin inhibits the growth of hepatocellular carcinoma (HCC) cells both in vivo and in vitro. Naringenin diminishes the ability of HCC cells to induce tube formation and migration of human umbilical vein endothelial cells (HUVECs) and suppresses neovascularization in chicken chorioallantoic membrane (CAM) assays. Meanwhile, in vivo results demonstrate that naringenin can significantly upregulate level of CD8⁺ T cells, subsequently increasing the level of immune-related cytokines in the tumor immune microenvironment. Mechanistically, we found that naringenin facilitate the K48-linked ubiquitination and subsequent protein degradation of vascular endothelial growth factor A (VEGFA) and mesenchymal-epithelial transition factor (c-Met), which reduces the expression of programmed death ligand 1 (PD-L1). Importantly, combination therapy naringenin with PD-L1 antibody or bevacizumab provided better therapeutic effects in liver cancer. Our study reveals that naringenin can effectively inhibit angiogenesis and anti-tumor immunity in liver cancer by degradation of VEGFA and c-Met in a K48-linked ubiquitination manner. This work enlightens the potential effect of naringenin as a promising therapeutic strategy against anti-angiogenesis and anti-tumor immunity in HCC.

Background::To address the need for immunotherapy in patients with advanced primary hepatocellular carcinoma (HCC), combination with radiotherapy (RT) has emerged as a promising strategy. In preclinical studies, irradiated tumors released tumor antigens to synergistically increase the antitumor effect of immunotherapy. Hence, we investigated whether RT enhances the efficacy of anti-programmed death receptor-1 (PD-1) inhibitors in advanced HCC in real-world practice.Methods::Between August 2018 and June 2021, 172 patients with advanced primary HCC were enrolled in the tertiary center (Zhongshan Hospital of Fudan University); 95 were treated with a combination of RT and the inhibitor of PD-1 (RT-PD1 cohort), and 77 were administered anti-PD-1 therapy (PD1 cohort). The first cycle of PD-1 inhibitors was administered within 60 days or concurrently with RT. Propensity score matching for bias reduction was used to evaluate the clinical outcomes.Results::Among 71 propensity-matched pairs, median progression-free survival was 5.7 months in the RT-PD1 cohort vs. 2.9 months in the PD1 cohort ( P <0.001). Median overall survival was 20.9 months in the RT-PD1 cohort vs. 11.2 months in the PD1 cohort ( P = 0.018). Compared with patients in the PD1 cohort, patients in the RT-PD1 cohort had significantly higher objective response rates (40.8%, 29/71 vs. 19.7%, 14/71, P = 0.006) and disease control rates (62.0%, 44/71 vs. 31.0%, 22/71, P <0.001). The incidences of toxic effects were not significantly different between the two cohorts. Conclusions::RT plus anti-PD-1 therapy is well tolerated. RT enhances the efficacy of anti-PD-1 therapy in patients with advanced primary HCC by improving survival outcomes without increased toxic effects.

Objective To investigate the impact of influence of personality traits of nurses as second victim and negative experience of nurses in adverse event and explore the intermediary roles of stress perception in influencing mechanism of negative experience.Methods Between March and April 2023,a convenience sampling method was employed to select 560 nurses from 3 general hospitals in Taiyuan City to conduct the study.The selected nurse all had experienced adverse events within last 3 months.The survey employed a general information questionnaire,Chinese big five personality questionnaire,second victim experience and support scale and Chinese version of stress perception scale.Pearson's correlation analysis was conducted to explore the correlation between the personality traits of nurses as second victim(specifically neuroticism),negative experiences and stress perception.The mediating role of stress perception between the neuroticism of nurses as second victim and negative experiences of nurses was analysed using PROCESS plug-in with the Bootstrap method.Results All of 560 distributed questionnaires were recovered,with a 100.00%of response rate.Personality traits of nurses as second victim were ranked in descending order with rigor,agreeableness,openness,neuroticism and extroversion.Both negative experiences and stress perception had higher scores(40.25±10.64 and 30.25±5.98,respectively).Neurotic personality in nurses as second victim was positively correlated with negative experience(r=0.528,P＜0.01)and stress perception(r=0.594,P＜0.01).Negative experiences showed a positive correlation with stress perception(r=0.339,P＜0.01).Neurotic personality of nurses as second victim had a significant direct impact on negative experiences[β=0.519,95%CI:0.318-0.720].As one of the stress perception dimensions,tension played a partial mediating role between neurotic personality in nurses as second victim and negative experience[β=0.148,95%CI:0.006-0.300],and a mediating effect percentage of 22.70%.Conclusions The neurotic personality of nurses as second victim can directly affect the negative experiences,either independently or in conjunction with tension.Nursing managers and nurses as second victims can reduce the negative experiences in adverse events by addressing higher neurotic personality and alleviating tension.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To explore the mechanism of turnover intention of junior nurses after adverse events from three aspects: work pressure, leadership style and personal characteristics.Methods:This study was a cross-sectional survey, using the convenience sampling method, 289 nurses from Shanxi Bethune Hospital from December 2020 to March 2022 were selected as the research subjects, and the general data questionnaire, the Separation Tendency Scale, the Nurses′ Work Stressor Scale, the Service-oriented Leadership Style Scale, and the Prospective Personality Scale were used to survey them.Results:Structural equation model showed that nurses′ job stressor level positively predicted turnover intention, with a path coefficient of 0.74, P<0.01, while service-oriented leadership style and forward-looking personality negatively predicted turnover intention, with path coefficients of -0.60 and -0.37, respectively, both P<0.01. Hierarchical regression analysis showed that both service-oriented leadership style and forward-looking personality negatively moderated the promotion of job stressors on turnover intention, and the moderating effect regression coefficients were -0.146, -0.215, both P<0.01. Conclusions:Hospitals should improve the prospective personality traits of junior nurses and cultivate the service-oriented leadership style of nursing managers after adverse events, so as to reduce the turnover tendency of junior nurses as the second victim, promote the improvement of nursing quality, and stabilize nursing team development.

Objective: To analyze the clinical features of perianal condyloma acuminatum in HIV infected men who have sex with men (MSM) and assess the effects of combined treatment of microwave and photodynamic therapy. Methods: Clinical and laboratory data of 260 male patients with perianal condyloma acuminatum were collected and microwave combined with photodynamic therapy was applied on them. Results: The majority of the patients with perianal condyloma acuminatum were young people (243/260). Warts were mainly located in the anus or from the outside to inside of the anus (245/260). Among them, the proportion of warts position of extraanal in HIV-infected group (8/220) was lower than that of non-HIV-infected group (7/40). HPV types 11 (70/118), 6 (44/118) and 16 (40/118) were the most common types of HPV infection. People with HIV infection were more likely to develop high-risk, mixed types HPV infection and multiple HPV infection than those without HIV infection. More than half of the patients (146/260) needed only 1-3 sessions of photodynamic treatments. There was no significant difference in the times of photodynamic treatments and the numbers of photosensitizers required between the HIV-infected and non-HIV-infected groups. The recurrence rate of HIV-infected group (13.6%, 30/220) was also similar to that of non-HIV-infected group (15.0%, 6/40), but far lower than those who underwent microwave therapy alone (45%, 18/40). Conclusions The combination therapy significantly reduced the recurrence rate of perianal condyloma acuminatum in HIV infected MSM.

Background As the main cellular constituent of corneal epithelium,corneal epithelial cells play critical roles in regulating and controlling the migration, proliferation and differentiation of cells during the repair of damage.MicroRNA (miRNA) is endogenously expressed small non-coding RNAs, which participates in a variety of biological processes.Previous studies demonstrated that miR-204 is highly expressed in normal corneal epithelium,but its function is still unclear.Objective This study was to investigate the function and mechanism of miR-204 in corneal epithelial cell proliferation.Methods Corneal epithelial tissue was collected during the corneal refractive surgery from the patients with refractive error under the informed consent, and human corneal epithelial cells(HCECs) were cultured and passaged.The relative expressing levels of miR-204 mRNA in the normal corneal epithelium and HCECs were detected by real time quantitative PCR.Cultured HCECs were evenly divided into three groups.The liposome with miR-204 mimic was transfected into the cells of the miR-204 mimic group, and blank liposome was transfected in the cells of the positive control group,and regularly cultured cells served as the normal control group.Cell proliferation capability was evaluated by colony-forming assay, and the percentage of the cells in different cell cycles was analyzed by flow cytometry.Western blot assay was employed to detect the expression levels of p-RB, E2F1 ,p27,CyclinA, CDC2, p-CDC2 and CDK2 proteins in the cells.Results The relative expression levels of miR-204 mRNA were 1.077 ±0.268 in the normal corneal epithelium and 0.041 ±0.018 in the HCECs, showing a significant difference between them (t =7.700,P＜0.001).The cloning cell number was evidently decreased in the miR-204 mimic group in comparison with the positive control group and normal control group.The percentage of cells in the G1 phase was 47.75％ in the miR-204 mimic group, which was significantly higher than 37.23％ in the positive control group and 40.72％ in the normal control group.The expression levels of E2F1 and p27 proteins in the cells were elevated (t=14.87,25.11;both at P＜0.01) and those of CDK2 and p-CDC2 proteins were decreased (t=5.39,10.65;both at P＜0.01) in the miR-204 mimic group in comparison with the positive control group.Conclusions The overexpression of miR-204 in the normal corneas probably is associated with non-proliferation status of corneal epithelial cells.Transfection of miR-204 into corneal epithelial cells can inhibit the proliferation of corneal epithelial cells probably by up-regulating the expression of E2F1 and p27 and suppressing the expression of CDK2/CyclinA and p-CDC2/CyclinA,which lead to cell arrest in G1 phase.