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

OBJECTIVES: To explore the therapeutic mechanism of compound Centella asiatica formula (CCA) for alleviating Schistosoma japonicum (Sj)-induced liver fibrosis in mice. METHODS: The active components and targets of CCA were identified using the TCMSP database with cross-analysis of Sj-related liver fibrosis targets. A "drug-component-target-pathway-disease" network was constructed using Cytoscape 3.9.1. Functional enrichment analysis (GO/KEGG) was performed using DAVID. Molecular docking study was carried out to validate interactions between the core targets and the key compounds. For experimental validation of the results, 36 mice were divided into control group, Sj-infected model group, and CCA-treated groups. In the latter two groups, liver fibrosis was induced via abdominal infection with Sj cercariae for 8 weeks, followed by 8 weeks of daily treatment with CCA decoction or saline. Hepatic pathology of the mice was assessedwith HE and Masson staining, and hepatic expressions of collagen-I and collagen-III were detected using immunohistochemistry; serum IL-6 and TNF-α levels were determined with ELISA. Hepatic expressions of TLR4 and MyD88 proteins were analyzed with Western blotting. RESULTS: We identified a total of 107 bioactive CCA components and 791 targets, including 37 intersection targets linked to Sj-induced fibrosis. The core targets included TNF, TP53, JUN, MMP9, and CXCL8, involving the IL-17 signaling, lipid metabolism, TLR4/MyD88 axis, and cancer pathways. Molecular docking study confirmed strong binding affinity between quercetin (a primary CCA component) and TNF/TP53/JUN/MMP9. In Sj-infected mouse models, CCA treatment significantly attenuated hepatic inflammatory cell infiltration, reduced collagen-I and collagen-III deposition, improved tissue architecture, reduced serum IL-6 and TNF-α levels, and downregulated TLR4 and MyD88 expressions in the liver. CONCLUSIONS CCA mitigates Sj-induced liver fibrosis by targeting TNF, TP53, JUN, and MMP9 to modulate the TLR4/MyD88 pathway, thereby suppressing pro-inflammatory cytokine release, inhibiting hepatic stellate cell activation, reducing collagen deposition, and preventing granuloma formation in the liver.
Animals ; Toll-Like Receptor 4/metabolism* ; Mice ; Myeloid Differentiation Factor 88/metabolism* ; Schistosoma japonicum ; Liver Cirrhosis/parasitology* ; Schistosomiasis japonica ; Signal Transduction ; Molecular Docking Simulation ; Inflammation ; Centella/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To compare the clinical efficacy of a fixed exoskeleton robot with that of an exoskeleton walker in training the balance of stroke survivors in the subacute stage.Methods:Thirty persons with subacute stroke were divided at random into a fixed robot group (15 cases) and a walking robot group (15 cases). In addition to conventional rehabilitation treatment, the fixed robot group underwent daily 20-minute treadmill-based fixed exoskeleton robot training, 5 days a week for 2 weeks. The walking group was trained with an exoskeleton walking robot on the same schedule. Before and after the treatment, the Berg balance scale, the sitting modified functional stretch test (SMFRT), an isokinetic muscle strength test and the modified Barthel index (MBI) were used to evaluate the subjects′ global balance, self-dynamic balance, knee proprioception and ability in the activities of daily living (ADL).Results:After the treatment, both groups′ average Berg score, SMFRT extension difference, proprioceptive absolute error angle in the affected knee and MBI had improved significantly. The average SMFRT extension difference after treatment in the walker group was then significantly better than the fixed robot group′s average. However, the fixed robot group′s proprioception in the affected knee joint was then significantly better, on average, than among the walking robot group.Conclusions:Both fixed exoskeleton robot training and exoskeleton walker training can improve the balance, proprioception and ADL ability after a stroke. The former better improves dynamic balance; the latter better improves proprioception in the affected knee joint.

Objective:To observe the application effect of dexmedetomidine combined with esketamine nasal drops in pediatric flexible bronchoscopy (referred to as bronchoscopy) surgery with spontaneous respiration retained.Methods:A total of 96 children undergoing bronchoscopy in the Changsha Hospital for Maternal & Child Health Care from May 2022 to December 2023 were selected and divided into the dexmedetomidine nasal drop group (group D, 47 cases) and the dexmedetomidine combined with esketamine nasal drop group (group DE, 49 cases) by random number table method. The mean arterial pressure (MAP), heart rate (HR), blood oxygen saturation (SpO 2) and respiratory rate (RR) of the two groups were observed before nasal drops (T 0), 30 minutes after nasal drops (T 1), 5 minutes after surgery started (T 2), and 10 minutes (T 3), 30 minutes (T 4), 60 minutes (T 5) and 120 minutes (T 6) after surgery. The separation anxiety and mask cooperation scores at T 1, modified Aldrete scores and Pediatric Anesthesia Emergence Delirium Scale (PEAD) scores at T 3-T 6 were evaluated; the number of children with PEAD score>10 was recorded, as well as the time to postoperatively take food and clear water. Results:There was no statistically significant difference in MAP and HR at T 0 between the two groups (all P>0.05); the MAP and HR of Group DE at T 1-T 6 were significantly higher than those of group D (all P<0.05). There was no statistically significant difference in SpO 2 and RR between the two groups within the group or between the groups at each time point (all P>0.05), while the incidence of hypoxemia (SpO 2≤92%) in group D at T 2 was significantly higher than that in group DE ( P<0.05). The separation anxiety and mask cooperation scores of group DE at T 1 were significantly better than those of group D ( P<0.05). The modified Aldrete scores of group DE at T 3, T 4 and T 5 were significantly higher than those of group D (all P<0.05). The PEAD score of group DE at T 3 was significantly lower than that of group D ( P=0.001); there was no statistically significant difference in PEAD scores between the two groups at T 4, T 5 and T 6 (all P>0.05), and no child in either group had PEAD scores>10 at T 4, T 5 and T 6. The time to take clear water and food in group DE was significantly earlier than that in group D (all P<0.05). Conclusions:In pediatric bronchoscopy surgery with spontaneous respiration retained, dexmedetomidine combined with esketamine nasal drops can more effectively relieve children′s separation anxiety, meet surgical needs, improve recovery quality, shorten the postoperative time to take food, and better implement the concept of enhanced recovery after surgery (ERAS) compared with dexmedetomidine alone.

Objective To investigate the requirement of blood sugar management in elderly patients with Type Ⅱ diabetes and to provide a reference for development of a program in management of blood sugar.Methods Using interpretive decriptive phenomenological research,an interview outline based on the theoretical domain framework was developed and face-to-face semi-structured interviews were conducted with 16 aged patients who had Type Ⅱ diabetes in the Department of Endocrinology and Metabolism of a Grade ⅢA hospital in Jiangxi Province.The participants were selected by purposive sampling.Colaizzi 7-step analytical method,in conjunction with Nvivo 11 software,was used to analyse,summarise and extract the themes.Results Seven themes related to the theoretical domain framework were extracted,which included knowledge,skills,environmental context and resources,behavioural adjustment,motivation and goals,emotions and self-efficacy.After refinement,nine sub-themes on major requirement for blood glucose management were extracted,which included the requirements for knowledge and skills in blood sugar management,support from the community and healthcare resources,support from the family,changes in maladaptive behaviours,individualised blood sugar management,motivation for self-management,clarity in goals of blood sugar control,emotional support and psychological adjustment,and support for strengthened beliefs(9 sub-themes).Conclusion Elderly patients with Type Ⅱ diabetes have diverse and individualised needs in management of blood sugar.In the future,healthcare staff should develop appropriate strategies or programs to meet the individual needs of patients by addressing the actual needs of patients,improving the self-management behaviours of patients so as to improve the effects of the blood sugar control.

Objective To analyze the differences and connections between the current grading and classification methods for nuclear medicine workplaces, and to provide technical guidance for environmental impact assessments and technical reviews. Methods By comparing the objects, purposes, and computational approaches between the two methods, this article illustrates the usage of both methods through specific examples and analyzes the relationship between them. Results The two methods differed in objects, purposes, and computational approaches. The A, B, and C grading scheme was primarily used to establish the level of administrative supervision for an entire nuclear medicine workplace. In contrast, the I, II, and III classification system specifies the hardware facilities and engineering protection requirements of internal places or rooms. Conclusion These two methods are complementary and collectively provide a complete framework for the assessment of nuclear medicine workplaces.

Objective:To investigate the incidence of common complications following vaginal delivery and analyze their influencing factors among women of reproductive age.Methods:This prospective cohort study consecutively enrolled women who delivered vaginally at two campuses of the Obstetrics and Gynecology Hospital of Fudan University between February and July 2023. Participants were categorized into groups according to complication occurrence: those with obstetric laceration versus those without, postpartum hemorrhage versus non-hemorrhage, and retained placenta/membranes without hemorrhage vs. non-retention. Data were collected using a self-developed questionnaire on risk factors for vaginal delivery complications. Group comparisons of demographics, obstetric history, intrapartum assessments, and delivery outcomes were performed using Chi-square test (or Fisher's exact test), independent samples t-test, and Mann-Whitney U test. Multivariate logistic regression identified risk factors for the three complication types. Results:Among 1 966 vaginal deliveries, the overall complication rate was 8.1% (159/1 966), with obstetric lacerations representing the most frequent complication at 4.6% (91/1 966), followed by postpartum hemorrhage at 2.7% (53/1 966) and retained placenta/membranes without hemorrhage at 1.4% (27/1 966). Multivariate logistic regression analysis identified distinct sets of independent risk factors for each complication. For obstetric lacerations, adequate gestational weight gain was associated with a reduced risk ( OR=0.547, 95% CI: 0.332-0.900, P=0.018), while precipitous labor ( OR=2.633, 95% CI: 1.321-5.248, P=0.006), shoulder dystocia ( OR=2.495, 95% CI: 1.093-5.691, P=0.030), poor maternal cooperation ( OR=1.887, 95% CI: 1.061-3.359, P=0.031), and specific perineal conditions—particularly reduced skin folds ( OR=2.341, 95% CI: 1.247-4.395, P=0.008) and tight/thick/edematous skin ( OR=2.511, 95% CI: 1.248-5.054, P=0.010)—emerged as significant risk factors. Regarding postpartum hemorrhage, conception through assisted reproductive technology ( OR=3.286, 95% CI: 1.189-9.076, P=0.022), presence of obstetric comorbidities ( OR=2.460, 95% CI: 1.070-5.656, P=0.034), elevated D-dimer levels ( OR=1.157, 95% CI: 1.049-1.277, P=0.004), reduced fibrinogen ( OR=0.521, 95% CI: 0.319-0.851, P=0.009), weak uterine contractions ( OR=20.175, 95% CI: 10.352-39.321, P<0.001), abnormal placentation ( OR=2.434, 95% CI: 1.167-5.078, P=0.018), and absence of early skin-to-skin contact ( OR=0.141, 95% CI: 0.067-0.295, P<0.001) were independently associated with increased risk. For retained placenta/membranes without hemorrhage, prolonged thrombin time ( OR=0.117, 95% CI: 0.034-0.318, P<0.001) and abnormal placentation ( OR=51.843, 95% CI: 14.988-179.324, P<0.001) were identified as primary risk factors. Conclusions:While the overall incidence of complications following vaginal delivery among women of reproductive age is relatively low, high-risk groups warrant particular attention. Precipitous labor, shoulder dystocia, poor maternal cooperation, and unfavorable perineal conditions increase laceration risk. Assisted conception, obstetric comorbidities, elevated D-dimer levels, uterine atony, and placental abnormalities elevate hemorrhage risk. Furthermore, placental abnormalities are strongly associated with retained placenta/membranes without hemorrhage.

Objective:To investigate the effect of continuous renal replacement therapy (CRRT) on energy metabolism and thermal balance in ICU patients with acute kidney injury (AKI).Methods:This study was a prospective observational study, which included AKI patients who underwent CRRT in ICU of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from May 2020 to December 2023. The patients' general clinical characteristics, comorbidities, body temperature, disease severity score, CRRT treatment time and filter lifespan were recorded. The concentrations of glucose and lactate in blood and ultrafiltrate, and the citrate level in the ultrafiltrate when regional citrate anticoagulation adopted were analyzed regularly. Subgroup analysis was carried out according to different anticoagulation modes and whether the patients with diabetes or shock. The changes of energy metabolism and thermal balance corresponding to the changes in glucose, lactate, citrate and body temperature induced by CRRT were calculated daily.Results:This study included 420 AKI patients undergoing CRRT. When the blood lactate was between 14-18 mmol/L, there was a loss of approximately 200-250 kcal of energy per day, while the blood lactate was between 6.5-11.5 mmol/L, the daily corresponding energy loss was about 100-150 kcal. During CRRT on the first day, the patients with diabetes or shock had a mild decrease of blood glucose, while patients without diabetes and shock had mild increase of blood glucose. When the target of blood glucose was gradually achieved, the mean daily increase of energy corresponding to blood glucose intake was about 100-130 kcal in patients undergoing CRRT. The mean daily increase of energy corresponding to citrate intake was approximately 330 kcal, when the patient was undertaken by CRRT with regional citrate anticoagulation. For every 1℃ decrease in body temperature, the mean daily heat loss caused by extracorporeal thermal radiation during CRRT was about 200 kcal.Conclusions:When conducting nutritional assessment and prescription for AKI patients supported by CRRT in the ICU, it is essential to fully consider the impact of CRRT on the patient's energy metabolism and heat balance. This includes the clearance of lactate, the balance of blood glucose, the intake of citrate, and the reduction in body temperature. Additionally, the type and stage of the disease, as well as individual differences, must be taken into account to achieve personalized nutritional assessment and precise implementation.

Objective:To observe and analyze the imaging features of pathologic myopic paravascular abnormalities (PVA) and macular retinoschisis (MRS) and their relationship with clinical features.Methods:A retrospective case series study. A total of 371 eyes of 224 patients with pathological myopia with PVA and/or MRS diagnosed by examination in Department of Ophthalmology of the First Affiliated Hospital of Zhengzhou University from September 2021 to December 2023 were included in the study. There were 74 eyes in 48 males and 297 eyes in 176 females. Age were 54 (49, 61) years; equivalent spherical lens (SE) was -13.375 (-18.00,-10.00) D. Axial length (AL) was 29.84 (28.27, 31.24) mm. According to the features of ultra-wide-angle sweep source optical coherence tomography, PVA morphology was divided into blood vessels and paravascular microfolds, paravascular retinal cysts, paravascular retinal splits and paravascular lamellar macular holes. MRS was divided into inner layer, outer layer and mixed layer according to splitting level, and grouped accordingly. The presence of dome-shaped macula (DSM), internal and external lamellar macular hole, and full lamellar macular hole (FTMH) were recorded. According to whether PVA combined with MRS or not, the affected eyes were divided into PVA group and PVA combined with MRS group. According to whether MRS involved the fovea, the affected eyes were divided into two groups: MRS not involved the fovea group and MRS involved the fovea group. Mann-Whitney U test was used to compare age, SE and AL among different groups. Qualitative data were compared by χ2 test. Results:In 371 eyes, there were 120 eyes in the simple PVA group; in the MRS group, there were 251 eyes, of which 208 eyes were in the PVA combined with MRS group. There were 33, 27, 3, 14, 12, 56, 28, and 7 eyes with or without retinal detachment, choroidal neovascularization, DSM, preretinal membrane, and simple superficial detachment of neuroepithelium in inner lamina, outer lamina, and FTMH, respectively. In 328 eyes with PVA, blood vessels and paravascular microfolds, paravascular retinal cysts, paravascular retinal splits and paravascular lamellar macular holes were 151, 236, 202 and 72 eyes, respectively. There were 142 eyes with single lesion (43.29%, 142/328). There were 186 eyes with 2 or more lesions (56.71%, 186/328). There were 34 eyes in the inner MRS group, 92 eyes in the outer MRS group and 125 eyes in the mixed MRS group, respectively. It involved 155 eyes in the fovea group; 96 eyes in the fovea group were not involved. There were significant differences in the number of PVA eyes between the outer MRS group, the inner MRS group and the mixed MRS group ( χ2=30.614, 28.379; P<0.001). Compared with PVA group, PVA group combined with MRS group was more likely to have two or more PVA lesions, the difference was statistically significant ( χ2=30.535, P<0.001). Compared with the inner MRS group and mixed MRS group, the age of the simple PVA group was younger, and the age of the outer MRS group was older, and the differences were statistically significant ( P<0.05). Compared with the inner MRS group and the outer MRS group, the simple PVA group had short AL, less myopia and better optimal corrected visual acuity (BCVA), while the mixed MRS group had long AL, more myopia and worse BCVA, and the differences were statistically significant ( P<0.05). Compared with the PVA group and the inner MRS group, the fovea was more involved in the outer MRS group and the mixed MRS group, and the difference was statistically significant ( χ2=3.906, 10.836; P<0.05). Those with MRS involved in fovea were older, AL was longer, myopia was more severe, and BCVA was worse ( P<0.001). DSM-associated splits were less likely to involve macula ( P<0.001). Conclusion:PVA and MRS exhibit a variety of presentations, and their imaging features correlate with clinical features.