Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To discuss the anti-tumor effect of low dose of methotrexate(MTX)combined with sorafenib(SFN)on the human osteosarcoma(OS),and to clarify the possible mechanism.Methods:Four types of human OS cells(143B cells,HOS cells,U2OS cells,and MG63 cells)were cultured in vitro.Western blotting method was used to detect the expression levels of vascular endothelial growth factor(VEGF)and vascular endothelial growth factor receptor 2(VEGFR2)proteins in the above four kinds of cells.The human OS xenograft model was established in the nude mice,and 20 successfully modeled BALB/C nude mice were randomly divided into control group(given 2％dimethyl sulfoxide+98％corn oil),low dose of MTX group(given 2 mng·kg-1 MTX),SFN group(given 15 mng·kg-1 SFN),and combined drug group(given 2 mng·kg-1 MTX+15 mng·kg-1 SFN);there were 5 mice in each group.The tumor volumes of the mice in various groups were detected and tumor growth curves were plotted;HE staining was used to observe the morphology of tumor tissue of the mice in various groups;immunohistochemistry was used to detect the positive expression rates of VEGFR2,proliferation marker Ki-67,and hypoxia-inducible factor-1(HIF-1)proteins in tumor tissue of the mice in various groups.The human OS 143B cells were divided into 0,0.125,0.250,0.500,1.000,2.000,and 4.000 μmol·L-1 MTX groups(given 0,0.125,0.250,0.500,1.000,2.000,and 4.000 μmol·L-1 MTX,respectively).CCK-8 method was used to detect the proliferation rates of the 143B cells in various groups,and half inhibityory concentration(IC50)was calculated;the concentration of MTX that had no effect on 143B cell survival was selected as low dose of MTX.The human OS 143B cells were divided into control and low dose of MTX groups(given 0 and 0.250 μmol·L-1 MTX).ELISA method was used to detect the levels of VEGF in the 143B cells in various groups.Results:Compared with 143B cells,the expression levels of VEGF and VEGFR2 proteins in the HOS cells,U2OS cells,and MG63 cells were significantly increased(P＜0.001).In the xenograft model,compared with control group,the tumor volumes of the mice in SFN group,and combined drug group were decreased(P＜0.001);compared with low dose of MTX group and SFN group,the tumor volume of the mice in combined drug group was decreased(P＜0.01).The immunohistochemical results showed that compared with control group,the positive expression rates of Ki-67,VEGFR2,and HIF-1 proteins in tumor tissue of the mice in combined drug group were significantly decreased(P＜0.05).The CCK-8 results showed that there was no change in the proliferation of the 143B cells treated with 0.25 μmol·L-1 MTX.The ELISA results showed that compared with control group,the level of VEGF in the 143B cells in MTX group was signyicantly decreased(P＜0.05).Conclusion:Low dose of MTX enhances the anti-tumor effect of SFN on the human OS,which may be due to the inhibition of VEGF secretion by the OS cells,thereby enhancing the anti-tumor effect of SFN on the human OS.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

As a physical treatment technique, modified electro-convulsive therapy (MECT) is used to treat mental and certain neurological disorders by causing seizures with short, suitable electrical currents applied to the brain while the patient is under general anesthesia and muscle relaxants. MECT is recognized for its therapeutic efficacy and clinical safety, rendering it one of the most prevalent interventions in psychiatric care. To enhance clinical outcomes and minimize adverse effects, this consensus document delineates the indications, therapeutic parameters, therapeutic procedures, potential adverse effects, and associated management strategies for MECT. These guidelines are informed by the latest clinical research and expert consensus, integrating evidence-based medicine methodologies. The objective is to furnish clinicians with precise operational guidelines and to advance the standardization of MECT practices in clinical settings.

The C 2-C 7 sagittal vertical axis (SVA) is an essential biomechanical parameter for evaluating cervical spine alignment, and it is integral to the pathogenesis, progression, and prognosis of cervical spine disorders. This parameter is widely used in evaluating cervical sagittal balance and functional status. Internationally, a C 2-C 7 SVA of less than 25 mm is considered within the cervical range for sagittal balance, while values exceeding 40 mm indicate cervical sagittal imbalance or deformity. An increased C 2-C 7 SVA disrupts cervical spine biomechanics, leading to heightened static and dynamic loads on the cervical musculature. This, in turn, results in muscle fatigue and discomfort. In the short term, patients may experience axial neck symptoms, while a sustained elevation in SVA over time significantly raises the risk of cervical disc degeneration, radiculopathy, and myelopathy. Additionally, a higher C 2-C 7 SVA postoperatively places excessive stress on adjacent spinal segments, which can accelerate degeneration of intervertebral discs and facet joints, contributing to adjacent segment degeneration. Both short-term and long-term postoperative evaluations have shown that an increase in C 2-C 7 SVA is typically associated with poorer surgical outcomes, whereas effective control of SVA values is closely linked to better functional recovery. Therefore, in clinical practice, maintaining C 2-C 7 SVA within the normal range (<25 mm) is critical not only for optimizing treatment results but also for significantly reducing postoperative complications and improving overall patient quality of life.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

OBJECTIVE: To investigate the effect of acupuncture on advanced cancer patients by meta-analysis. METHODS: Nine databases (the Cochrane Central Register of Controlled Trials, MEDLINE, Web of Science, Embase, China National Knowledge Infrastructure, the Cumulative Index to Nursing and Allied Health Literature, Chinese Biomedical Literature Database, China Science and Technology Journal Database, and WanFang Data) were searched for randomized controlled trials (RCTs) on acupuncture in advanced cancer patients published from inception to February 13, 2023 and updated to June 1, 2023. Primary outcomes were quality of life (QOL), while secondary outcomes were pain, fatigue, and adverse events (side effects). Data synthesis was performed using RevMan V.5.3 to calculate pooled effect sizes. RoB-2 was used for the risk of bias, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. RESULTS: Totally 17 RCTs involving 1,178 participants were included, 15 of which were pooled for meta-analysis. Most studies demonstrated some concern for the overall risk of bias. The pooled data indicated that acupuncture was associated with improved QOL [mean difference (MD)=6.67, 95% confidence interval (CI): 5.09 to 8.26], pain (MD=-1.18, 95% CI -2.28 to -0.08), and adverse events (risk ratio=0.30, 95% CI: 0.26 to 0.57) compared with control groups. Fatigue outcome was not included. Heterogeneity was substantial, and GRADE evidence was very low for both QOL and pain. CONCLUSIONS Acupuncture could benefit patients with advanced cancer and is considered safe compared with usual care. However, the evidence regarding QOL and pain outcomes requires further validation. It is crucial to encourage the development of high-quality studies to strengthen this evidence. (Registry No. CRD42023423539).
Humans ; Acupuncture Therapy ; Neoplasms/therapy* ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To explore the relationships between social support,positive coping,caregiver burden and family resilience of primary caregivers of first-stroke patients.Methods A questionnaire survey was conducted among 307 primary caregivers of first-stroke patients in 2 tertiary hospitals in Shanghai by convenience sampling method.Social support rating scale,simplified coping style questionnaire,Zarit caregiver burden interview,and family resilience assessment scale were used for questionnaire survey.Pearson correlation analysis and structural equation models were used for data analysis.Results A total of 288 valid questionnaires were collected,and the effective recovery rate was 93.81％.Pearson correlation analysis showed that there was a positive correlation between family resilience and social support,family resilience and positive coping,and social support and positive coping(r=0.375,0.627,and 0.277;all P＜0.01),while caregiver burden and social support,caregiver burden and positive coping,and family resilience and caregiver burden were all negatively correlated(r=-0.203,-0.343,and-0.444;all P＜0.01).The mediating effect model was constructed with positive coping and caregiver burden as mediating variables,social support as independent variables,and family resilience as dependent variables.The results showed that social support could mediate family resilience through positive coping,with a mediating effect of 0.164,accounting for 26.1％of the total effect;social support could also affect the family resilience of the primary caregivers of first-stroke patients through the partial chain mediating effect of positive coping and caregiver burden,with a mediating effect value of 0.032,accounting for 5.1％of the total effect.Conclusion Social support can predict family resilience among primary caregivers of first-stroke patients,and positive coping and caregiver burden play chain mediating roles in the impact of social support on family resilience.

This study explored the drying kinetics of Salviae Miltiorrhizae Radix et Rhizoma(SM), established the suitable models simulating the drying kinetics, and then analyzed the dynamic changes of active components during the drying processes with different methods, aiming to provide a basis for the establishment of suitable drying methods and the quality control of SM. The drying kinetics were studied based on the drying curve, drying rate, moisture effective diffusion coefficient, and drying activation energy, and the appropriate drying kinetics model of SM was established. The drying performance of different methods, such as hot air drying, infrared drying, and microwave drying of SM was evaluated, and the changes in the content of 10 salvianolic acids and 6 tanshinones during drying were analyzed by UPLC-TQ-MS. The Technique for Order Preference by Similarity to an Ideal Solution(TOPSIS) was employed to evaluate the quality of SM dried with different methods. The results showed that the drying rate and moisture effective diffusion coefficient of SM increased with the rise in drying temperature, and the maximum drying rates of different methods were in the order of microwave drying > infrared drying > hot air drying, slice > whole root. The drying rate decreased with the rise in temperature and the extension of drying time. The activation energy of hot air drying was higher than that of infrared drying in SM. The most suitable model for simulating the drying process of SM was the Page model. The TOPSIS results suggested infrared drying at 50 ℃ was the optimal drying method for SM. During the drying process, the content of salvianolic acids increased in different degrees with the loss of moisture, among which salvianolic acid B showed the largest increase of 44 times compared with that in the fresh medicinal material. Tanshinones also existed in the fresh herb of SM, and the content of tanshinone Ⅱ_A increased by 3 times after drying. The results provided a basis for the establishment of suitable drying methods and the quality control of SM.
Salvia miltiorrhiza/chemistry* ; Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Rhizome/chemistry* ; Kinetics ; Quality Control ; Abietanes