AIM:To explore the role and molecular mechanism of Men1 gene in regulating mouse renal fibro-sis.METHODS:A unilateral ureteral obstruction(UUO)-induced renal fibrosis model was established using C57BL/6 mice,and the mice were randomly divided into 4 groups:sham,UUO-3 d,UUO-7 d,and UUO-14 d,with 15 mice in each group.The C57BL/6 mice with Men1 knockout were randomly divided into 4 groups:sham-Men1-WT,sham-Men1-CKO,UUO-Men1-WT,and UUO-Men1-CKO,with 8 mice in each group.HE staining,Masson staining,and Sirius red staining were used to detect UUO-induced renal injury and renal fibrosis.Human renal tubular epithelial HK-2 cells with MEN1 knockout were constructed.RT-qPCR,Western blot,immunohistochemistry and immunoflurorescnence were per-formed to detect the mRNA and protein expression of MEN1,fibrosis markers(α-smooth muscle actin,collagen type Ⅲ and fibronectin 1)and m6A-related proteins[methyltransferase-like 3(METTL3),METTL14,YTH domain family pro-tein 2(YTHDF2),AlkB homolog 5(ALKBH5),and fat mass and obesity-associated protein(FTO)]in UUO mouse kid-ney tissues and transforming growth factor-β(TGF-β;10 μg/L)-treated HK-2 cells.Dot blot analysis was conducted to measure m6A methylation levels in both mouse kidney tissuess and HK-2 cells.RESULTS:The expression of Men1 de-creased with the aggravation of renal fibrosis(P＜0.01).Men1 inhibited the expression of fibrosis markers in renal tis-sues,and MEN1 knockout increased the accumulation of collagen induced by UUO and TGF-β(P＜0.01).The expres-sion of FTO and ALKBH5 in mouse kidney tissues and HK-2 cells was down-regulated by MEN1 knockout(P＜0.01),and the methylation level of m6A was increased(P＜0.01).Overexpression of FTO significantly reduced the accumulation of m6A modifications and renal fibrosis caused by MEN1 loss,and the methylation level of m6A was increased(P＜0.01).CONCLUSION:Loss of Men1 gene promotes renal fibrosis in mice,and Men1 suppresses renal fibrosis in mice by pro-moting the expression of FTO/ALKBH5 to reduce m6A modifications.

AIM:To explore the role and molecular mechanism of Men1 gene in regulating mouse renal fibro-sis.METHODS:A unilateral ureteral obstruction(UUO)-induced renal fibrosis model was established using C57BL/6 mice,and the mice were randomly divided into 4 groups:sham,UUO-3 d,UUO-7 d,and UUO-14 d,with 15 mice in each group.The C57BL/6 mice with Men1 knockout were randomly divided into 4 groups:sham-Men1-WT,sham-Men1-CKO,UUO-Men1-WT,and UUO-Men1-CKO,with 8 mice in each group.HE staining,Masson staining,and Sirius red staining were used to detect UUO-induced renal injury and renal fibrosis.Human renal tubular epithelial HK-2 cells with MEN1 knockout were constructed.RT-qPCR,Western blot,immunohistochemistry and immunoflurorescnence were per-formed to detect the mRNA and protein expression of MEN1,fibrosis markers(α-smooth muscle actin,collagen type Ⅲ and fibronectin 1)and m6A-related proteins[methyltransferase-like 3(METTL3),METTL14,YTH domain family pro-tein 2(YTHDF2),AlkB homolog 5(ALKBH5),and fat mass and obesity-associated protein(FTO)]in UUO mouse kid-ney tissues and transforming growth factor-β(TGF-β;10 μg/L)-treated HK-2 cells.Dot blot analysis was conducted to measure m6A methylation levels in both mouse kidney tissuess and HK-2 cells.RESULTS:The expression of Men1 de-creased with the aggravation of renal fibrosis(P＜0.01).Men1 inhibited the expression of fibrosis markers in renal tis-sues,and MEN1 knockout increased the accumulation of collagen induced by UUO and TGF-β(P＜0.01).The expres-sion of FTO and ALKBH5 in mouse kidney tissues and HK-2 cells was down-regulated by MEN1 knockout(P＜0.01),and the methylation level of m6A was increased(P＜0.01).Overexpression of FTO significantly reduced the accumulation of m6A modifications and renal fibrosis caused by MEN1 loss,and the methylation level of m6A was increased(P＜0.01).CONCLUSION:Loss of Men1 gene promotes renal fibrosis in mice,and Men1 suppresses renal fibrosis in mice by pro-moting the expression of FTO/ALKBH5 to reduce m6A modifications.

BACKGROUND: Regenerative medicine by using stem cells from dental pulp is promising for treating patients with critical limb ischemic (CLI). Here, we investigated the difference in the angiogenetic ability of stem cells from human exfoliated deciduous teeth (SHED) and human dental pulp stem cells (DPSC). METHODS: SHED and DPSC were harvested from dental pulp and analyzed in flow- cytometry for detecting the expression of surface markers. Levels of angiogenetic marker were examined by RT-PCR and Western-blot. Eighteen immunodeficient mice of critical limb ischemic model were divided into three groups: SHED, DPSC and saline, which was administered with SHED, DPSC or saline intramuscularly. Histological examination was performed to detect the regenerative results. RESULTS: A highly expression of CD146 was detected in SHED. Moreover, cells with negative expression of both CD146 and CD31 in SHED were more in comparison with those in DPSC. Expression of angiogenesis factors including CXCL12, CXCR4, Hif-1a, CD31, VEGF and bFGF were significant higher in SHED than DPSC by the RT-PCR and Western-Blot results. SHED induced more CD31 expression and less fibrous tissue formation in the critical limb ischemic model as compare with DPSC and saline. CONCLUSION Both SHED and DPSC possessed the ability of repairing CLI. With expressing more proangiogenesis factors, SHED may have the advantage of repairing CLI.

Objective:To construct the quality evaluation system for tracheal extubation in the patients undergoing general anesthesia based on zero-defect management theory.Methods:Based on the model of zero-defect theory, literature review, semi-structured interviews, expert consultation and analytic hierarchy process were used to determine the content and weight of each index of the quality evaluation system for tracheal extubation in the patients undergoing general anesthesia.Results:The effective recovery rates of the two rounds of expert consultation questionnaires were 93% and 96% respectively; the expert authority coefficients were 0.946 and 0.947 respectively; the Kendall harmony coefficients were 0.247 and 0.250 respectively ( P<0.001). The final evaluation index system included 3 first-level indicators, 11 second-level indicators and 48 third-level indicators.The consistency coefficients of indicators at all levels were <0.1. Conclusions:The quality evaluation system for endotracheal extubation constructed for patients undergoing general anesthesia is highly scientific and reliable and can provide a basis for the quality evaluation of and continuous improvement in endotracheal extubation in the patients undergoing general anesthesia.

Objective:To construct a core competence evaluation index system for Anesthesia Intensive Care Unit (AICU) nurses, and to provide reference for the career orientation, training and management of AICU nurses.Methods:The first draft of the core competence evaluation index system of AICU nurses was developed by literature evaluation, semi-structured interview and group discussion. Using the purposive sampling method, 26 experts were selected for 2 rounds of expert consultation from August to September 2021 to determine the evaluation index system of core competence of AICU nurses, and the weights of indicators at all levels were determined by analytic hierarchy process.Results:The effective recovery rates of the 2 rounds of expert letter consultation questionnaire were respectively 92.31% (24/26) and 91.67% (22/24) , the expert authority coefficients were respectively 0.93 and 0.93, and the Kendall's harmony coefficients were respectively 0.28 and 0.19 (all P<0.01) . The final evaluation index system of AICU nurses' core competence included 4 first-level indicators (theoretical knowledge, nursing practice, comprehensive ability, personal characteristics) , 14 second-level indicators and 52 third-level indicators. Conclusions:The constructed evaluation index system of core competence of AICU nurses is scientific and reliable, which can provide a reference for the career orientation, training and management of AICU nurses.

Objective: To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R). Methods: Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared. Results: Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05). Conclusion Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.

Objective: To preliminary, explore the effect of small intestinal epithelial dendritic cells on the occurrence and development of nonalcoholic fatty liver disease in mice. Methods: Thirty-two (half male and half female) 4-week-old C57BL/6 mice were randomly divided into two groups. The mice were fed with normal diet (SD group) and high-fat diet (HFD group). Eight mice (half male and half female) were randomly killed from each group over the 14 and 20-weeks feeding period to observe their body weight, liver and small-intestine wet weight. Alanine aminotransferase, aspartate aminotransferase, blood glucose, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglyceride were determined by eyeball blood samples. Pathological diagnosis and alcoholic fatty liver disease activity score were collected. The number of mice small intestinal dendritic cells was observed under a microscope. Statistical analysis was performed to compare two groups of independent samples with homogeneity test of variance, t test, and covariance analysis. Results: The body weight, liver wet weight, serum alanine aminotransferase and aspartate aminotransferase of mice in HFD group were significantly higher than those of control group at 20 weeks (P < 0.05), and the serum high density lipoprotein of mice in HFD group was significantly higher than that of SD group at 14 weeks (P < 0.05). At 14th weeks, the liver tissue of mice in HFD group had early pathological manifestations of hepatitis (fatty degeneration, punctate necrosis and balloon-like degeneration). Of which 87.5% (7/8) of them were diagnosed as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while only a few mice in SD group had early pathological manifestations of hepatitis. At 20th weeks, all mice in HFD group were diagnosed with non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while none of the mice in SD group was diagnosed with non-alcoholic fatty liver disease. At both time points, the percentage of small intestinal dendritic cells in HFD group was significantly higher than that in SD group (14 weeks: 4.181 ± 4.314 vs. 15.099 ± 10.349; 20 weeks: 9.615 ± 8.267 vs. 32.839 ± 24.475, both P < 0.05). Statistical analysis combined with the alcoholic fatty liver disease activity score showed that there was no linear correlation between the two groups (regression coefficient was 20.196%). Conclusion The number and different staging of small intestinal dendritic cells in mice is associated with the occurrence and development of NAFLD.

OBJECTIVE: To explore the correlation of genetic mutations and clinical features of myelodysplastic syndromes (MDS) with scores of Revised International Prognostic Scoring System (IPSS-R). METHODS: Eighty-seven patients with de novo MDS were enrolled. Mutations of MDS-related genes and clinical features were used to determine the incidence and subtype of mutations. Clinical features and IPSS-R scores of the patients with high frequency mutations involving TET2, TP53, ASXL1, RUNX1 and SF3B1 genes were compared. RESULTS: Fifty-four patients (62.1%) harbored at least one point mutation. The incidences of various mutations were significantly different, with the incidence of MDS-EB-2 being 100% and MDS-SLD being only 38.9%. Compared with the wild types, patients harboring mutations had higher lactate dehydrogenase, higher β2 microglobulin, higher percentage of bone marrow blast cells and lower hemoglobin levels (P=0.027, <0.01, <0.01, 0.046, respectively). The IPSS-R scores of MDS patients with mutations were significantly higher than the wild types (P<0.01). The IPSS-R scores of the TP53 mutation groups were 7.82±1.83, which was significantly higher than the control group (3.77±1.66, P<0.01). No difference was found between the IPSS-R between patients carrying TET2, ASXL1, RUNX1, and SF3B1 mutations or the wild types (P>0.05). CONCLUSION Genetic mutations are commonly found in MDS. MDS patients with mutations have unique clinical laboratory characteristics. Although the prognostic value of most genes is controversial, TP53 is an definite indicator of poor prognosis.
DNA Mutational Analysis ; Humans ; Incidence ; Mutation ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Tumor Suppressor Protein p53 ; genetics

Background:The pathogenesis of irritable bowel syndrome(IBS)is not fully known,social psychological factor is the important factor of IBS,especially the relationship with anxiety and depression. Aims:To investigate psychological stress factor,anxiety and depression in IBS patients among soldiers in northeast area. Methods:A total of 11 400 soldiers in northeast area were enrolled by multistage,stratified,cluster random sampling method asking to fulfill a questionnaire on IBS. Zung self-rating anxiety scale(SAS)and Zung self-rating depression scale(SDS)were assessed,and the relationship with anxiety,depression and stress was analyzed. Results:The incidence of IBS was 15. 9% . Prevalences of anxiety and depression in IBS group were significantly higher than those in non-IBS group(22. 9% vs. 9. 6% ,26. 6% vs. 12. 4% ,P< 0. 05). Score of SAS and SDS in IBS group were significantly higher than those in non-IBS group(50. 86 ± 7. 27 vs. 36. 54 ± 6. 97,53. 47 ± 7. 86 vs. 38. 25 ± 9. 83,P < 0. 05). Positive correlation was found between score of SAS and SDS and stress factors such as feeling lonely,depression,intensive training,working pressure,poor relationship with colleagues,solving emergency event or participating in military exercises in IBS group(P < 0. 05). Conclusions:IBS in soldiers is related with stress and psychological factors.

A total of 17 cases with pelvic limb hyperhidrosis were selected for lumbar sympathetic nerve modulation.The puncture of lumbar sympathetic nerve was guided by computed tomography (CT) through the gap of L2-3 until the needle tip reached the lateral of the second or third lumbar vertebra body and outside of psoas major.A mixture of 1％ lidocaine 3 ml and 30％ Iohexol injection 0.3 ml was injected.If the diffusion of lidocaine was observed between lumbar vertebra body and psoas major.After 15 min,5 ml of absolute alcohol was injected to modulate the lumbar sympathetic nerve.After 5 min,oximetry-derived perfusion index of toe and sole temperature increased (5.9 ± 1.4) folds and (4.16± 0.89) ℃ on average respectively.Pelvic limb hyperhidrosis was all cured within 6 months and one case recurred after a year.There were no occurrences of complications.Lumbar sympathetic nerve modulation guided by CT may be used for treating female pelvic limbs hyperhidrosis.