OBJECTIVES: To investigate the effect of pachymic acid on brown/beige adipocyte differentiation and lipid metabolism in preadipocytes. METHODS: 3T3-L1 MBX cells were induced to differentiate into beige adipocytes using a brown cocktail method. The impact of pachymic acid on the viability of 3T3-L1 MBX cells was evaluated using the CCK-8 assay. The formation of lipid droplets following treatment with pachymic acid was observed by oil red O staining. The mRNA expression levels of key browning genes, including uncoupling protein (Ucp) 1, the peroxisome proliferator activated receptor-γ coactivator (Pgc)-1α, and the PR domain-containing protein 16 (Prdm16), as well as the mRNA expression of sterol regulatory element-binding protein (Srebp) 1c, acetyl-coA carboxylase (Acc), fatty acid synthase (Fas), and hormone-sensitive triglyceride lipase (Hsl), adipose triglyceride lipase (Atgl), and carnitine palmitoyltransferase (Cpt) 1 were detected by quantitative reverse transcription polymerase chain reaction. The protein expression of Ucp1, Pgc-1a, and Prdm16 was detected by Western blotting. RESULTS: The 3T3-L1 MBX cells were induced in vitro to form beige adipocytes with high expression of key browning genes(Ucp1, Pgc-1α, and Prdm16), and beige adipose-marker genes (Cd137, Tbx1, and Tmem26). Concentrations range of 0-80 μmol/L pachymic acid were non-cytotoxic to 3T3-L1 MBX cells. Pachymic acid treatment significantly inhibited the differentiation of 3T3-L1 MBX cells, resulting in a notable decrease in lipid accumulation. There was a marked increase in the expression of key browning genes and their proteins products, such as Ucp1, Pgc-1α, and Prdm16, while the expressions of fat synthesis-related genes Srebp1c, Acc and Fas were significantly decreased (all P<0.05). The expressions of lipolysis-related genes (Hsl, Atgl, and Cpt1) were significantly increased (all P<0.05). Treatment with 20 μmol/L pachymic acid showed the most pronounced effect. CONCLUSIONS Pachymic acid can inhibit fat synthesis and promote lipid decomposition by regulating the brown formation and lipid differentiation of preadipocytes.
Animals ; Lipid Metabolism/drug effects* ; Mice ; Cell Differentiation/drug effects* ; Adipocytes, Beige/drug effects* ; 3T3-L1 Cells ; Adipocytes, Brown/drug effects* ; Triterpenes/pharmacology* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Uncoupling Protein 1 ; Sterol Regulatory Element Binding Protein 1/metabolism*

OBJECTIVES: To investigate the role of METTL3 and FOXO3 in anthracycline resistance in acute myeloid leukemia (AML) cells. METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptome sequencing (RNA-seq) were performed in anthracycline-resistant and sensitive HL60 and K562 cells with lentivirus-mediated knockdown or overexpression of METTL3 and FOXO3. TCGA and GSE6891 datasets were used for analysis of the clinical and gene expression data of AMI patients. FOXO3 expressions at the mRNA and protein levels in the transfected cells were detected with RT-qPCR and Western blotting, and the changes in cell proliferation and apoptosis were evaluated using CCK8 assay and flow cytometry; the expression of m⁶A-modified mRNA and mRNA stability of FOXO3 was detected analyzed using MeRIP-qPCR and RT-qPCR. Functional enrichment analysis of the differential genes in the transfected cells was performed. RESULTS: Differential gene analysis in anthracycline-resistant versus sensitive AML cells and in cells with METTL3 knockdown revealed the enrichment in FoxO and autophagy pathways (P<0.05), and the anthracycline-resistant cells showed significantly increased m⁶A modification of FOXO3. FOXO3 expression was positively correlated with METTL3 expression. METTL3 knockdown significantly reduced FOXO3 mRNA stability and its protein levels in anthracycline-resistant AML cells, which exhibited higher m6A-modified FOXO3 expression levels than their sensitive counterparts. Database analysis, Kaplan-Meier analysis and RT-qPCR results suggested that a high FOXO3 expression was associated with a poor prognosis of AML patients. In anthracycline-resistant AML cells expressing higher FOXO3 levels than the sensitive cells, lentivirus-mediated overexpression of FOXO3 significantly enhanced cell proliferation and suppressed cell apoptosis. Inhibiting autophagy using an autophagy inhibitor (Baf.A1) obviously enhanced the inhibitory effect of adriamycin on resistant AMI cells and cells overexpressing FOXO3. CONCLUSIONS METTL3 promotes FOXO3 expression via m6A modification, and FOXO3-driven autophagy contributes to anthracycline resistance in AML cells by enhancing cell proliferation and suppressing cell apoptosis.
Humans ; Forkhead Box Protein O3/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Drug Resistance, Neoplasm ; Methyltransferases/genetics* ; Autophagy ; Anthracyclines/pharmacology* ; HL-60 Cells ; Apoptosis ; Cell Proliferation ; K562 Cells

Objective To evaluate clinical efficacy and safety of ABO-incompatible (ABOi) living-related kidney transplantation. Methods Clinical data of 23 recipients undergoing ABOi living-related kidney transplantation were retrospectively analyzed. According to the initial blood group antibody titers in the recipients before surgery, different individualized pretreatment regimens were adopted, including oral intake of immunosuppressive drugs plus rituximab, or oral intake of immunosuppressive drugs plus plasma exchange and/or double filtration plasmapheresis plus rituximab. The blood group antibody titers before and after pretreatment, before and after kidney transplantation, and perioperative renal function and related complications were monitored. Renal allograft function and related complications were observed during postoperative follow-up. Results Among 23 recipients undergoing ABOi living-related kidney transplantation, except for one case presenting with hyperacute rejection during operation, the serum creatinine levels of the remaining 22 recipients were restored normal. Perioperative complications included lymphatic fistula in 4 cases, 1 case of urinary fistula, 1 case of perirenal hematoma complicated with T cell-mediated rejection, 6 cases of urinary system infection, 1 case of acute tubular necrosis, 1 case of acute pancreatitis, 1 case of blood group antibody titer rebound, and 1 case of primary disease recurrence, and all of these complications were cured after corresponding treatment. During postoperative follow-up, the graft and recipient survival rates of 22 recipients were 100%, and renal allograft function was normal. The blood group antibody titer were all ≤1:8 during follow-up. Complications during follow-up included 2 cases of severe lung infection, 1 case of antibody-mediated rejection, 2 cases of primary disease recurrence, 1 case of lymphocyst, 1 case of urinary system infection, 1 case of herpes zoster, 1 case of BK viruria and 2 cases of abnormal blood glucose levels. Conclusions ABOi living-related kidney transplantation may be safely performed by selecting individualized pretreatment regimens according to antibody titers by different blood groups. However, high-dose rituximab or combined use of rabbit anti-human thymocyte immunoglobulin may cause severe infectious complications in highly sensitized recipients.

Objective:To explore the current situation of nursing human caring in hospital wards and analyze its influencing factors, so as to facilitate the development of nursing human caring practice.Methods:From July to November 2022, a total of 107 hospitals were surveyed through stratified convenience sampling method, and 4 072 ward nursing managers were recruited to finish the general information questionnaire and the ward nursing human caring status questionnaire. The general information included the region, class and type of the hospital, etc. The ward nursing human caring status questionnaire included 38 items in 5 dimensions of nursing human caring system and process, humanistic quality and training of nursing staff, humanistic environment and facilities, human caring procedures and measures, and human caring quality evaluation and improvement, with a full score of 190 points. Descriptive statistics were used to analyze the general data, independent samples t-test, ANOVA and correlation analysis were used to analyze the factors influencing the current status of nursing human caring in the ward, while multiple linear regression analysis was used to conduct a multivariate analysis. Results:The score of nursing human caring in hospital wards was 156.91±27.78. Whether the hospital had carried out nursing human caring pilot(demonstration) wards, whether the ward had previously been a hospital nursing human caring pilot(demonstration) nursing unit, the type of ward, and whether nursing managers had participated in human caring training were the influencing factors of the implication of nursing humanistic caring in wards( P<0.05). Conclusions:The practice of nursing human caring in hospital wards is at a good level, but needs to be further strengthened. Nursing managers should take systematically strategies to promote the development of nursing human caring practice.

Objective:To explore the mediating effects of self-efficacy between leadership empowerment behavior and neglect of care among senior care workers.Methods:In this cross-sectional study, from July to September 2020, totally 423 senior care workers from 50 nursing institutions for the aged in Jining, Jiaozuo, and Shijiazhuang were selected by convenient sampling and investigated with the General Information Questionnaire, Leadership Empowerment Behavior Scale, Self-Efficacy Scale, and Nursing Caregiver Negligence Assessment Scale. Pearson's correlation analysis was used to analyze the correlation of each variable, and bootstrapping was employed to test the mediating effect.Results:In this study, 423 questionnaires were distributed and 386 valid questionnaires were recovered. The total score of leadership empowerment behavior of 386 care workers was (47.93±7.51) ; the total score of self-efficacy was (28.65±5.92) ; the total score of neglecting care was (73.04±8.80) . The leadership empowerment behavior, self-efficacy, and neglect of care in the senior care workers were positively correlated ( P<0.01) . Self-efficacy played a partial mediating role between leadership empowerment and neglect of care, and the mediating effect accounted for 19.73%. Conclusions:The neglect of care in the senior care workers is at a low level, and self-efficacy plays a partial mediating role between leadership empowerment and neglect of care. Leaders of nursing institutions for the aged should improve their level of empowerment behaviors and strengthen the self-efficacy of senior care workers, so as to reduce the neglect of care among senior care workers.

Atrial fibrillation (AF) is one of the most common complications after cardiac surgery. The existing treatment of postoperative AF mainly focuses on preoperative prevention, intraoperative protection and postoperative treatment for factors prone to AF before, during and after surgery, but the postoperative treatment in various areas and hospitals is different. This article combines the latest literature published in Europace about the practice guidance of cardioversion of AF and atrial flutter, and summarizes the treatment of electrical cardioversion, in order to provide clinical guidance for electrical cardioversion of AF after cardiac surgery.

Objective:To observe the effect of ruxolitinib combined with glucocorticoid on cytomegalovirus (CMV) activation in patients with acute graft-versus-host disease (aGVHD) .Methods:The clinical data of 195 patients who underwent allogeneic hematopoietic stem cell transplantation in the Department of Hematology of the First Medical Center of the People’s Liberation Army General Hospital from August 2018 to September 2020 were retrospectively analyzed. According to the severity of aGVHD, the patients were divided into the non-GVHD group, aGVHD grade Ⅰ group, aGVHD grade Ⅱ-Ⅳ group, and aGVHD grade Ⅲ/Ⅳ group. In addition, they were classified into two subgroups according to the first-line treatment regimen for aGVHD: combined regimen group (ruxolitinib combined with glucocorticoid) and classical regimen group (glucocorticoid alone) . The cumulative incidence of CMV activation, the duration of CMV activation, and the duration of CMV negativity in each subgroup at 90 and 180 days after transplantation were analyzed. The overall survival and disease-free survival rates of patients in both regimens were compared.Results:Sixty-four (32.8%) patients in the group did not develop aGVHD. The numbers of patients with grade Ⅰ, Ⅱ-Ⅳ, and Ⅲ/Ⅳ aGVHD were 30 (15.4%) , 101 (51.8%) , and 14 (7.2%) , respectively. Compared with patients in the classical regimen, no significant difference was observed in the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity in patients with grade Ⅰ-Ⅳ aGVHD in the combined regimen at 90 and 180 days after transplantation ( P>0.05) . Further analysis of patients with grade Ⅱ-Ⅳ and Ⅲ/Ⅳ aGVHD showed that the cumulative incidence of CMV activation, duration of CMV activation, and duration of CMV negativity did not show significant difference between the two treatment regimens ( P>0.05) . In addition, there was no significant difference in the overall survival and disease-free survival rates of patients in both regimens ( P>0.05) . Conclusion:Ruxolitinib combined with glucocorticoid as the first-line therapy for aGVHD did not increase the risk of CMV activation.

With the accelerated aging of the global population, the problem of elder abuse has become increasingly prominent, among which mental abuse is the type with the highest incidence. Mental abuse seriously damages the mental health of the elderly, increases their risk of illness and suicide, and reduces the quality of life of the elderly. This article combs the relevant research on mental abuse of the elderly at home and abroad in detail, introduces the definition, assessment tools and the current situation of mental abuse, and summarizes the corresponding influencing factors from the three levels of the elderly, caregivers and society, and aims at providing a basis for further research on the intervention of mental abuse of the elderly and the prevention of the occurrence of mental abuse.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directlycontribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Objective: To investigate the effect of glyphosate on blood routine of occupational exposure population. Methods: The workers who were occupationally exposed to glyphosate were selected as exposure group, and administrative staffs who were not exposed to glyphosate were selected as control group. Occupational health examination was conducted on all the subjects, and personal monitoring was applied to detect the concentration of glyphosate in the air of workplace. Time weighted average (TWA) concentration was calculated by the result of determination. Statistical methods were employed to compare the difference of blood routine results between the contact group and the control group, as well as between different posts. Results: 178 glyphosate workers were included in the contact group, and 203 non-contact persons were included in the control group. There was no statistically significant difference in the equilibrium test between the two groups(P>0.05). The abnormal rate of blood routine in the exposure group and the control group were 70.8% and 69.0%, respectively, but the difference was not statistically significant (P>0.05). Compared with the control group, the red blood cell count and platelet distribution width difference (P<0.05) were significant difference. There was no significant difference between different positions (P>0.05). Conclusion When TWA value is below 9.40 mg/m³, glyphosate has effect on the results of platelet distribution width and red blood cell count, but has no effect on the abnormal rate of blood routine.