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

Infectious diseases of the respiratory system are very common in clinical practice,among which pneumonia caused by in-fluenza virus infection is characterized by high morbidity and mortality.Current clinical treatments for respiratory viral infections still face challenges such as drug resistance and poor efficacy.Necroptosis,a form of programmed cell death,is closely associated with the progression of respiratory viral infections.Traditional Chinese medicine modulating necroptosis has demonstrated beneficial therapeu-tic effects in these diseases.This paper introduces the concept and mechanisms of necroptosis,reviews recent research on the relation-ship between necroptosis and respiratory virus infections diseases,and summarizes the therapeutic effects of traditional Chinese medi-cine in regulating necroptosis to intervene in these diseases,aiming to provide insights for the development and clinical application of therapeutic agents for respiratory viral infections.

OBJECTIVE To explore the clinical characteristics of patients with hematologic tumors combined with Fusarium infection and analyze the prevention and control measures.METHODS Six patients with hematologic neo-plasms combined with Fusarium infection diagnosed at the First Medical Center of the People's Liberation Army General Hospital from Apr.2019 to Dec.2023 were selected as research objects.Through retrospective analysis of patients' clinical data,the clinical manifestations,diagnosis,treatment and prevention strategies of Fusarium in-fection in hematologic neoplasms were analyzed.RESULTS All six patients with hematologic neoplasms combined with Fusarium infection were neutropenic or deficient patients,with main symptoms including moderate fever,painful skin nodules,rash,skin broken and crusted,and scrotal swelling and pain.Patients with severe neutrophil deficiency were susceptible to blood-borne Fusobacterium infections.Four patients had a markedly elevated G-test and Fusorium was first detected by microbiome metagenomic next-generation sequencing(mNGS)in blood,earli-er than traditional pathogenic culture methods.Five patients had Fusarium detected in urine or stool cultures.All six patients received empirical antibacterial and antifungal treatments,but the fungal infection treatment effects were poor.Treatment was adjusted according to the pathogenetic findings,mainly using a combination regimen based on liposomal amphotericin B or posaconazole tablets,with three patients cured and three death.Two pa-tients were from the same ward with a sixteen-day interval.Although no evidence of infection transmission was found,there was still a risk of cross-infection in patients with hematological malignancies and severe immunodefi-ciency.Measures for the prevention and control of hospital-acquired infections were implemented for patients with Fusarium infection and the ward.CONCLUSIONS The clinical manifestations of patients with hematological tumors combined with Fusarium infection are complex and varied with high mortality rates.MNGS testing is valuable in the early diagnosis of Fusarium infection,and it is necessary to explore new treatment options and hospital-ac-quired infectious disease prevention and control measures to improve the prognosis.

OBJECTIVE To explore the clinical characteristics of patients with hematologic tumors combined with Fusarium infection and analyze the prevention and control measures.METHODS Six patients with hematologic neo-plasms combined with Fusarium infection diagnosed at the First Medical Center of the People's Liberation Army General Hospital from Apr.2019 to Dec.2023 were selected as research objects.Through retrospective analysis of patients' clinical data,the clinical manifestations,diagnosis,treatment and prevention strategies of Fusarium in-fection in hematologic neoplasms were analyzed.RESULTS All six patients with hematologic neoplasms combined with Fusarium infection were neutropenic or deficient patients,with main symptoms including moderate fever,painful skin nodules,rash,skin broken and crusted,and scrotal swelling and pain.Patients with severe neutrophil deficiency were susceptible to blood-borne Fusobacterium infections.Four patients had a markedly elevated G-test and Fusorium was first detected by microbiome metagenomic next-generation sequencing(mNGS)in blood,earli-er than traditional pathogenic culture methods.Five patients had Fusarium detected in urine or stool cultures.All six patients received empirical antibacterial and antifungal treatments,but the fungal infection treatment effects were poor.Treatment was adjusted according to the pathogenetic findings,mainly using a combination regimen based on liposomal amphotericin B or posaconazole tablets,with three patients cured and three death.Two pa-tients were from the same ward with a sixteen-day interval.Although no evidence of infection transmission was found,there was still a risk of cross-infection in patients with hematological malignancies and severe immunodefi-ciency.Measures for the prevention and control of hospital-acquired infections were implemented for patients with Fusarium infection and the ward.CONCLUSIONS The clinical manifestations of patients with hematological tumors combined with Fusarium infection are complex and varied with high mortality rates.MNGS testing is valuable in the early diagnosis of Fusarium infection,and it is necessary to explore new treatment options and hospital-ac-quired infectious disease prevention and control measures to improve the prognosis.

Objective:To analyze and explore the diagnostic value of endoscopic submucosal dissection (ESD) for primary gastrointestinal lymphoma (PGIL).Methods:A retrospective analysis was conducted on the clinical and pathological data from 37 patients with suspected PGIL and admitted to Zhongshan Hospital, Fudan University and Xiamen Hospital, Zhongshan Hospital, Fudan University between January 2021 and December 2023. The diagnostic accuracy for PGIL of initial endoscopic conventional biopsies was compared with that of ESD biopsies.Results:Among these patients, 6 were diagnosed as having primary gastrointestinal lymphoma by routine endoscopic biopsy, with a diagnostic rate of 16.22% (6/37). Of the 22 patients who underwent ESD, 20 were diagnosed as having primary gastrointestinal lymphoma, achieving a diagnostic rate of 90.91% (20/22), which was significantly higher than that of initial endoscopic routine biopsies ( χ2=31.228, P<0.05). Conclusion:ESD demonstrates significant diagnostic value for PGIL.

Objective:To investigate the contributing factors to elevated blood pressure in borderline cases during medical selection for recruitment of Air Force flying cadets in order to enhance the accuracy of selection.Methods:Blood pressure was measured among 2 350 male high school graduates in the 2022 re-selection phase of medical selection of Air Force flying cadets. None of the participants had a family history of hypertension according to previous health checkups. Identified through blood pressure measurement, subjects with borderline hypertension were assigned to an intervention group (self-intervention with personalized correction plans) and a control group (self-intervention alone) using a random number table. Standardized blood pressure measurements and comprehensive medical history reviews were performed to compare pre- and post-intervention outcomes across the 2 groups, followed by an investigation into the causative mechanisms of elevated blood pressure.Results:Among the 102 cases of borderline hypertension (51 per group) identified, primary contributing factors included the white-coat phenomenon (41.2%), pre-examination physical activity (17.6%), pre-examination medications (3.9%) and poor sleep quality (35.3%). No significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) were observed between the 2 groups at baseline (both P>0.05). After interventions, the intervention group showed significantly lower SBP ( t=3.13, P=0.002) and DBP ( t=7.68, P<0.001) than the control group. Both groups exhibited reductions in SBP and DBP from baseline ( t=6.63, 8.97, 4.13, 2.03, P<0.001, <0.001, <0.001, =0.043). The percentage of students with normal blood pressure was 96.1% (49/51) in the intervention group and 78.4% (40/51) in the control group. Conclusions:Transient blood pressure elevation in selection settings primarily stems from the white-coat phenomenon, physical exertion, medications and sleep disturbances. Standardizing blood pressure measurement protocols and addressing transient factors can help avoid unwarranted disqualifications and ensure the accuracy of selection.

Infectious diseases of the respiratory system are very common in clinical practice,among which pneumonia caused by in-fluenza virus infection is characterized by high morbidity and mortality.Current clinical treatments for respiratory viral infections still face challenges such as drug resistance and poor efficacy.Necroptosis,a form of programmed cell death,is closely associated with the progression of respiratory viral infections.Traditional Chinese medicine modulating necroptosis has demonstrated beneficial therapeu-tic effects in these diseases.This paper introduces the concept and mechanisms of necroptosis,reviews recent research on the relation-ship between necroptosis and respiratory virus infections diseases,and summarizes the therapeutic effects of traditional Chinese medi-cine in regulating necroptosis to intervene in these diseases,aiming to provide insights for the development and clinical application of therapeutic agents for respiratory viral infections.

Objective:To analyze and explore the diagnostic value of endoscopic submucosal dissection (ESD) for primary gastrointestinal lymphoma (PGIL).Methods:A retrospective analysis was conducted on the clinical and pathological data from 37 patients with suspected PGIL and admitted to Zhongshan Hospital, Fudan University and Xiamen Hospital, Zhongshan Hospital, Fudan University between January 2021 and December 2023. The diagnostic accuracy for PGIL of initial endoscopic conventional biopsies was compared with that of ESD biopsies.Results:Among these patients, 6 were diagnosed as having primary gastrointestinal lymphoma by routine endoscopic biopsy, with a diagnostic rate of 16.22% (6/37). Of the 22 patients who underwent ESD, 20 were diagnosed as having primary gastrointestinal lymphoma, achieving a diagnostic rate of 90.91% (20/22), which was significantly higher than that of initial endoscopic routine biopsies ( χ2=31.228, P<0.05). Conclusion:ESD demonstrates significant diagnostic value for PGIL.

Objective:To investigate the contributing factors to elevated blood pressure in borderline cases during medical selection for recruitment of Air Force flying cadets in order to enhance the accuracy of selection.Methods:Blood pressure was measured among 2 350 male high school graduates in the 2022 re-selection phase of medical selection of Air Force flying cadets. None of the participants had a family history of hypertension according to previous health checkups. Identified through blood pressure measurement, subjects with borderline hypertension were assigned to an intervention group (self-intervention with personalized correction plans) and a control group (self-intervention alone) using a random number table. Standardized blood pressure measurements and comprehensive medical history reviews were performed to compare pre- and post-intervention outcomes across the 2 groups, followed by an investigation into the causative mechanisms of elevated blood pressure.Results:Among the 102 cases of borderline hypertension (51 per group) identified, primary contributing factors included the white-coat phenomenon (41.2%), pre-examination physical activity (17.6%), pre-examination medications (3.9%) and poor sleep quality (35.3%). No significant differences in systolic blood pressure (SBP) or diastolic blood pressure (DBP) were observed between the 2 groups at baseline (both P>0.05). After interventions, the intervention group showed significantly lower SBP ( t=3.13, P=0.002) and DBP ( t=7.68, P<0.001) than the control group. Both groups exhibited reductions in SBP and DBP from baseline ( t=6.63, 8.97, 4.13, 2.03, P<0.001, <0.001, <0.001, =0.043). The percentage of students with normal blood pressure was 96.1% (49/51) in the intervention group and 78.4% (40/51) in the control group. Conclusions:Transient blood pressure elevation in selection settings primarily stems from the white-coat phenomenon, physical exertion, medications and sleep disturbances. Standardizing blood pressure measurement protocols and addressing transient factors can help avoid unwarranted disqualifications and ensure the accuracy of selection.