Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.

Objective To observe clinical efficacy of Danggui Yinzi prescription combined with focused ultrasound in treatment of vulvar lichen sclerosus(VLS)with blood deficiency and dryness.Methods A total of 60 patients with blood deficiency and dryness VLS hospitalized in Gansu Provincial Hospital of Traditional Chinese Medicine from September 2023 to September 2024 were selected as study subjects,they were divided into control group(n=30)and treatment group(n=30)by random number table method.Control group was treated with focused ultrasound,and treatment group was treated with oral Danggui Yinzi prescription on the basis of control group.After 1 month of treatment,symptom scores(skin lesion area,color,etc.)and clinical efficacy of two groups were compared.Results After treatment,symptom scores of two groups were lower than those before treatment,and symptom scores of treatment group were lower than those of control group.Total effective rate of treatment group was higher than that of control group(P＜0.05).Conclusion Danggui Yinzi prescription combined with focused ultrasound is effective in treatment of VLS with blood deficiency and dryness,which can significantly reduce or eliminate itching symptoms and promote skin healing.

Objective To explore the effect of psychological flexibility based psychotherapy model on cancer-related fatigue in lung cancer patients.Methods A total of 60 lung cancer patients admitted to Zhejiang Cancer Hospital from March 2022 to December 2023 were selected as research subjects.They were divided into control group(n=30)and study group(n=30)by using a random number table method.Control group received routine psychological intervention,while study group was treated with a psychological flexibility-based therapy model in addition to the routine intervention.The scores of anxiety self-rating scales,depression self-rating scales,perceived burden,coping strategies,and cancer-related fatigue were compared between two groups.Results After intervention,the self-assessment scale scores of anxiety and depression,self-perceived burden and cancer-related fatigue in both groups decreased,and the reduction was more significant in study group(P＜0.05).The coping style scores of both groups improved,and the improvement was more significant in study group(P＜0.05).Conclusion Intervention with a psychological flexibility-based psychotherapy model in lung cancer patients can reduce negative emotions,self-perception burden and cancer-related fatigue,and improve patients' coping style.

Objective To observe clinical efficacy of Danggui Yinzi prescription combined with focused ultrasound in treatment of vulvar lichen sclerosus(VLS)with blood deficiency and dryness.Methods A total of 60 patients with blood deficiency and dryness VLS hospitalized in Gansu Provincial Hospital of Traditional Chinese Medicine from September 2023 to September 2024 were selected as study subjects,they were divided into control group(n=30)and treatment group(n=30)by random number table method.Control group was treated with focused ultrasound,and treatment group was treated with oral Danggui Yinzi prescription on the basis of control group.After 1 month of treatment,symptom scores(skin lesion area,color,etc.)and clinical efficacy of two groups were compared.Results After treatment,symptom scores of two groups were lower than those before treatment,and symptom scores of treatment group were lower than those of control group.Total effective rate of treatment group was higher than that of control group(P＜0.05).Conclusion Danggui Yinzi prescription combined with focused ultrasound is effective in treatment of VLS with blood deficiency and dryness,which can significantly reduce or eliminate itching symptoms and promote skin healing.

Objective To explore the effect of psychological flexibility based psychotherapy model on cancer-related fatigue in lung cancer patients.Methods A total of 60 lung cancer patients admitted to Zhejiang Cancer Hospital from March 2022 to December 2023 were selected as research subjects.They were divided into control group(n=30)and study group(n=30)by using a random number table method.Control group received routine psychological intervention,while study group was treated with a psychological flexibility-based therapy model in addition to the routine intervention.The scores of anxiety self-rating scales,depression self-rating scales,perceived burden,coping strategies,and cancer-related fatigue were compared between two groups.Results After intervention,the self-assessment scale scores of anxiety and depression,self-perceived burden and cancer-related fatigue in both groups decreased,and the reduction was more significant in study group(P＜0.05).The coping style scores of both groups improved,and the improvement was more significant in study group(P＜0.05).Conclusion Intervention with a psychological flexibility-based psychotherapy model in lung cancer patients can reduce negative emotions,self-perception burden and cancer-related fatigue,and improve patients' coping style.

Objective:To investigate the regulatory role of miR-146a in the maintenance of homeostasis and function of conventional dendritic cells (cDCs).Methods:Bone marrow-derived dendritic cells (BMDCs) from wild-type (WT) and miR-146a knockout (miR-146a KO) mice were cultured in vitro. RT-PCR was used to analyze miR-146a expression in BMDCs stimulated by Toll-like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) or TLR9 ligand CpG oligonucleotide (CpG-ODN); flow cytometry was performed to assess the expression of MHCⅡ and co-stimulatory markers (CD86 and CD80); RT-PCR and ELISA were used to measure the expression of cytokines at mRNA and protein levels, respectively; the influence of miR-146a-deficient BMDCs on CD4 + OTⅡT cell proliferation and differentiation was analyzed through in vitro co-culture and in vivo adoptive transfer experiments; flow cytometry was used to analyze the changes in the proportions of splenic DCs subsets in mice; the regulatory role of miR-146a in maintaining splenic DC homeostasis was further investigated using miR-146a KO mice and bone marrow chimeric models. Two-tailed t test was used for statistical analysis. Results:Following the stimulation with TLR4/9 ligands, miR-146a expression was significantly enhanced in BMDCs from WT mice ( P<0.01); the expression of MHCⅡ and CD86 in BMDCs from miR-146a KO mice were higher than in those from WT mice (all P<0.01). Following CpG-ODN stimulation, IL-12 and IL-6 expression at both mRNA and protein levels were higher in BMDCs from miR-146a KO mice than in those from WT mice (all P<0.05). However, no statistically significant differences in IL-12 or IL-6 expression were observed after LPS stimulation (all P>0.05). CpG-ODN-activated BMDCs demonstrated a robust capability to promote the proliferation of CD4 + OTⅡT cells and induced Th1/Th17 cell polarization (all P<0.01). Compared with WT mice, miR-146a KO mice showed a significant reduction in the CD11c + CD11b highcDC subsets in the spleen ( P<0.01). Bone marrow chimeric mice further confirmed that miR-146a played a critical role in maintaining the homeostasis of splenic CD11c + CD11b highcDC subsets. Conclusion:miR-146a regulates the homeostasis and function of cDC subsets, suggesting its potential for developing novel DC-based therapeutic strategies against microbial infections.

Objective:To investigate the role of miR-146a in regulating the homeostasis and function of epidermal Langerhans cells (LCs).Methods:Fresh and in vitro cultured epidermal LCs were isolated and purified by flow cytometry (FCM). The expression of miR-146a in LCs was detected by quantitative PCR (qPCR). The percentages of epidermal LCs in wild-type (WT) and miR-146a conventional knockout (miR-146a cKO) mice were analyzed by FCM. The expression of major histocompatibility complex Ⅱ (MHCⅡ) and co-stimulatory molecules (CD86 and CD80) was analyzed by FCM to evaluate the effect of miR-146a on the maturation of LCs. The percentage of Dextran-FITC + LCs was detected by FCM to evaluate the effect of miR-146a on the phagocytic function of LCs. In vitro and in vivo experiments were used to analyze the ability of miR-146a-deficient and -sufficient LCs to stimulate the proliferation of CD8 + OT-ⅠT cells and CD4 + OT-Ⅱ T cells. Results:The expression of miR-146a was significantly increased in mature LCs than in the freshly isolated LCs. There was no significant difference in the number of epidermal LCs between wild-type (WT) and miR-146a cKO mice. After a 48 h culture in vitro, the expression of MHCⅡ, CD86 and CD80 in the epidermal LCs of miR-146a cKO mice was similar to that of WT mice. Moreover, miR-146a deletion had no significant influence on antigen uptake by LCs. However, miR-146a deficiency enhanced the antigen-presenting ability of LCs that could stimulate the proliferation of OVA-specific CD8 + OT-Ⅰ T cells and CD4 + OT-Ⅱ T cells. Conclusions:miR-146a had no influence on the homeostasis, maturation and phagocytosis of LCs, but enhanced the antigen-presenting function.

Objective:To investigate the role of chemokine receptor CX3CR1 in chronic skin inflammation and its regulatory mechanism.Methods:Wild type (WT) C57BL/6 mice and Cx3 cr1 GFP/GFP mice were induced by DNFB to establish acute and chronic allergic contact dermatitis (ACD) model. Ear inflammation and swelling were observed with hematoxylin-eosin (HE) staining. Flow cytometry (FCM) was used to detect the changes in classical Langerhans cell (LC) and monocyte-derived LC (Mo-LC), as well as the expression of major histocompatibility complex Ⅱ (MHCⅡ), inducible nitric oxide synthase (iNOS) and TNF-α. Changes in epidermal LC in UV irradiation-induced dermatitis models were also analyzed. In human chronic skin inflammation, CX3CL1 expression was detected using immunohistochemistry, RT-PCR and Western blot and CD1a, CD14 and CD207 expression was observed with immunofluorescence staining. Results:In the chronic ACD model, Cx3 cr1 GFP/GFP mice showed significantly alleviated ear inflammatory and swelling as compared with WT mice, but no significant difference was found in the acute ACD model. The percentages of Mo-LC were decreased in the chronic ACD model and after three weeks of UV irradiation. Moreover, MHCⅡ, TNF-α and iNOS expressed by Mo-LC were significantly upregulated as compared with those by classical LC. CX3CL1 expression was significantly upregulated and the numbers of CD14 + monocytes and CD1a + langerin - Mo-LC were dramatically increased in human chronic skin inflammation. Conclusions:CX3CR1 might maintain inflammatory response by regulating local remodeling of Mo-LC in chronic skin inflammation.

Objective:To explore the correlation between cancer fear and coping style in patients after laparoscopic radical resection for liver cancer.Methods:From February 2017 to October 2020, convenience sampling was used to select 1 320 patients undergoing laparoscopic radical resection for liver cancer in the Department of Abdominal Surgery of Zhejiang Cancer Hospital as the research object. The general information questionnaire, Chinese version of the Short Form of the Fear of Progression Questionnaire (FoP-Q-SF) and the Medical Coping Modes Questionnaire (MCMQ) were used for the survey. Pearson correlation was used to analyze the correlation between patients' cancer fear and coping style. A total of 1 320 questionnaires were distributed and 1 308 valid questionnaires were returned with the valid response rate of 99.09%.Results:Among 1 308 patients, the total score of the Chinese version of FoP-Q-SF was (36.51±6.23), and 56.65% (741/1 308) patients scored more than 34 points. There were statistically significant differences in the Chinese version of the FoP-Q-SF scores of patients with different gender, age, marital status, economic pressure caused by the disease, number of hospitalizations for liver cancer, and cancer family history after laparoscopic radical resection of liver cancer ( P<0.01). The confrontation dimension scores of patients in MCMQ were lower than the domestic norm, and the avoidance and resignation dimension scores were higher than the domestic norm, and the differences were statistically significant ( P<0.01). The total score and dimension scores of the Chinese version of FoP-Q-SF were negatively correlated with the confrontation dimension score of the MCMQ ( P<0.01), and positively correlated with the resignation and avoidance dimension scores ( P<0.01) . Conclusions:More than half of the cancer fear of patients after laparoscopic radical resection of liver cancer exceeds the normal level, and those who adopt avoidance and resignation methods to face the disease have a high level of fear. Nursing staff should provide targeted nursing interventions according to the emotional level of different patients, and help patients establish positive coping styles.