BackgroundSchizophrenia is a complex， chronic and severe mental disorder， and the pathogenesis of which has not been fully elucidated. The abnormalities in lipid metabolism and circulating metabolomes have already been implicated in the pathophysiology of schizophrenia. However， available studies have mainly focused on a few liposomes and circulating metabolites， failing to systematically reveal the mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia. ObjectiveTo uncover mediating role of circulating metabolomes in the causal relationship between liposomes and schizophrenia， thereby providing biomarkers and potential therapeutic targets for the prevention and treatment of schizophrenia. MethodsData from Genome-Wide Association Studies （GWAS） were analyzed， taking data on 179 liposomes as exposure variables， data on 123 circulating metabolites as intermediate variables， and data on schizophrenia as outcome variable. A two-step， two-sample Mendelian randomization analysis was conducted using the inverse-variance weighted （IVW）， MR- Egger， Weighted median， and Weighted mode methods to study the causal relationship of liposomes with schizophrenia and the mediating role of circulating metabolomes in the relationship. ResultsIVW model identified 8 lipids associated with schizophrenia without reverse causality. There were 5 circulating metabolomes strongly associated with schizophrenia. Acetate played a significant mediating role in the causal relationship between phosphatidylinositol （18：0_18：2） and schizophrenia （P=0.023， 95% CI： 0.036~0.532）， accounting for 28.4% of the causal relationship. ConclusionThis study demonstrates a causal relationship between liposomes and schizophrenia， with phosphatidylinositol being a risk factor in the progression of schizophrenia， and acetate playing a mediating role in this process. ［Fund by National Natural Science Foundation of China General Program （number， 82271546）； Shanxi Merit Funding for Overseas Students Sci-Tech Activities Project （number， 20240041）； Shanxi Province Science and Technology Innovation Leading Talent Team Project （number， 202304051001049）； Shanxi Scientific Research Foundation for the Returned Overseas Chinese Scholars （number， 2022-190）； "Six Measures for Health Care Prosperity" Specialized Research Program （number， Y2024008）］

OBJECTIVES: To investigate the role and mechanism of Brahma-related gene 1 (Brg1) in regulating the Wnt/β-catenin signaling pathway in a bronchopulmonary dysplasia (BPD) model. METHODS: Wild-type C57BL/6 and Brg1^f1/f1 mice were randomly divided into four groups: wild-type control, wild-type BPD, Brg1^f1/f1 control, and Brg1^f1/f1 BPD (n=5 each). Immortalized mouse pulmonary alveolar type 2 cells (imPAC2) were cultured, and Brg1 gene was knocked down using lentivirus transfection technology. Cells were divided into three groups: control, empty vector, and Brg1 knockdown. Hematoxylin and eosin staining and immunofluorescence were used to detect pathological changes in mouse lung tissue. Western blot and real-time fluorescent quantitative PCR were used to measure Brg1 protein and mRNA expression levels in mouse lung tissue. Western blot and immunofluorescence were used to detect the expression of homeodomain-containing protein homeobox (HOPX), surfactant protein C (SPC), and Wnt/β-catenin signaling pathway proteins in mouse lung tissue and imPAC2 cells. The CCK8 assay was used to assess the proliferation of imPAC2 cells, and co-immunoprecipitation was performed to verify the interaction between Brg1 and β-catenin proteins in imPAC2 cells. RESULTS: Compared to the Brg1^f1/f1 control group and wild-type BPD group, the Brg1^f1/f1 BPD group showed increased alveolar diameter and SPC protein expression, and decreased relative density of pulmonary vasculature and HOPX protein expression (P<0.05). Compared to the control group, the Brg1 knockdown group showed increased cell proliferation ability, protein expression levels of SPC, Wnt5a and β-catenin, and β-catenin protein fluorescence intensity, along with decreased HOPX protein expression (P<0.05). An interaction between Brg1 and β-catenin proteins was confirmed. CONCLUSIONS The Brg1 gene may promote the proliferation of alveolar type 2 epithelial cells by regulating the Wnt/β-catenin signaling pathway, thus influencing the occurrence and development of BPD.
Animals ; DNA Helicases/genetics* ; Transcription Factors/genetics* ; Wnt Signaling Pathway/physiology* ; Nuclear Proteins/genetics* ; Mice ; Bronchopulmonary Dysplasia/etiology* ; Mice, Inbred C57BL ; beta Catenin/physiology* ; Disease Models, Animal ; Cell Proliferation ; Lung/pathology* ; Male

OBJECTIVE: To investigate the expression of specific AT sequence binding protein 1 (SATB1) in diffuse large B cell lymphoma (DLBCL) and its relationship with clinicopathological features and prognosis. METHODS: A total of 68 cases of initially diagnosed with DLBCL at Guangxi Medical University Affiliated Tumor Hospital between January 2008 to December 2015 were enrolled. The expression of SATB1 were detected by Immunohistochemistry on paraffin embedded tissue of patients. The relationship between the expression of SATB1 and clinicopathological features and prognosis in patients with DLBCL was analyzed. RESULTS: SATB1 protein was mainly expressed in cytoplasm of lymphoma cell. The rate of SATB1 expression in DLBCL tissues was 66.2% (46/68). The positive rate of SATB1 in patients with ECOG score of 0-1 was higher than that in patients with ECOG score ≥2 (P <0.05). The 5-year progression-free survival (PFS) and 5-year overall survival (OS) in positive and negative SATB1 groups were 55.5% and 23.5%, respectively (P =0.045), and 65.6% and 34.9%, respectively (P <0.001). Univariate analysis showed that positive expression of SATB1 was associated with good OS of patients. Multivariate analysis showed that chemotherapy cycles less than 4 and elevated LDH were independent adverse prognostic factor for OS in DLBCL patients, with positive SATB1 expression as a protective factor. CONCLUSION The positive expression of SATB1 is closely associated with a lower ECOG score and a favorable prognosis in patients with DLBCL.
Humans ; Lymphoma, Large B-Cell, Diffuse/metabolism* ; Matrix Attachment Region Binding Proteins/metabolism* ; Prognosis ; Female ; Male ; Middle Aged ; Immunohistochemistry ; Adult

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

Objective: To establish anin vitromodel of ferroptosis induced by Erastin and RAS-selective lethal 3(RSL3) in hepatoma cells, and to provide theoretical basis for the development of novel therapeutic strategies for HCC. Methods: Hepatoma cells(HCCLM3, HepG2, Hep3B, Huh7 and PLC/PRF/5) in logarithmic growth phase were treated with Erastin(0-40 μmol/L) and RSL3(0-10 μmol/L) at double concentrations respectively. After 24 h, CCK-8 method was used to detect cell viability, draw growth curve, calculate IC50, and HCC cells sensitive to inducers were selected for follow-up experiments. The effect of inducer on the state of hepatoma cells was observed under light microscope, and immunoblotting and flow cytometry were used to verify whether the ferroptotic modelin vitrowas successfully constructed. Results: Huh7, Hep3B and HepG2 cells were sensitive to Erastin and RSL3, but HCCLM3 and PLC/PRF/5 were insensitive to Erastin and RSL3. When the concentration of Erastin and RSL3 reached the maximum, the survival rate was still above 65%. Huh7, Hep3B and HepG2 cells were selected for subsequent experiments. Compared with the control group, the expression of Glutathione peroxidase 4(GPX4), a ferroptotic marker, was down-regulated in a concentration-dependent manner. In Huh7, Hep3B and HepG2 cells, lipid reactive oxygen species(ROS) levels significantly increased after 24 h treatment with 10 μmol/L and 20 μmol/L Erastin, respectively; in Huh7 cells, lipid ROS levels significantly increased after 24 h treatment with 0.5 μmol/L and 1 μmol/L RSL3, respectively; in Hep3B and HepG2 cells, lipid ROS levels significantly increased after 24 h treatment with 1 μmol/L and 2 μmol/L RSL3, respectively, compared with control group. Conclusion Huh7, Hep3B and HepG2 cells are highly sensitive to Erastin and RSL3. Huh7, Hep3B and HepG2 cells treated with 10 μmol/L Erastin for 24 h are good models for simulating ferroptosis induced by Erastinin vitro, Huh7 cells treated with 0.5 μmol/L RSL3 for 24 h and Hep3B and HepG2 cells treated with 1 μmol/L RSL3 for 24 h are good models for simulating ferroptosis induced by RSL3in vitro.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

Visual hallucination(VH)is a common symptom of schizophrenia,the underlying mechanism has not been fully elucidated.It has been found that the dysfunction of dopamine(DA)system,the overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)receptor in glutamate system and the dysfunction of γ-aminobutyric acid(GABA)ergic neurons can induce VH in patients with schizophrenia.In addition,abnormalities in brain structural and functional networks and visual networks are also closely related to the occurrence of VH.The purpose of this paper is to review the neurochemistry and nerve injury mechanism of VH in schizophrenic patients to deeply understand the characteristics of VH,and make more accurate judgment in the early diagnosis,condition evaluation and treatment plan of schizophrenic patients.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with electroacupuncture in the treatment of postoperative pain of hemorrhoids with qi stagnation and blood stasis type.Methods A total of 150 patients with postoperative pain of hemorrhoids of qi stagnation and blood stasis type were randomly divided into observation group,control group and routine group,with 50 cases in each group.The routine group was given routine anti-inflammatory and supportive treatment.The control group was given thumb-tack needling for subcutaeous embedding therapy on the basis of routine group treatment.The observation group was given electroacupuncture treatment on the basis of control group treatment.A total of six days of treatments were given.After six days of treatment,the clinical efficacy of the three groups was evaluated,and the changes of Visual Analogue Scale(VAS)of pain scores were observed before and after treatment in the three groups.The changes of 5-hydroxytryptamine(5-HT),calcitonin-related gene peptide(CGRP),norepinephrine(NE),substance P(SP)and β-endorphin(β-EP)were compared before and after treatment in the three groups.Results(1)The effective rate of the observation group was 36.00%(18/50),the control group was 14.00%(7/50),and the routine group was 4.00%(2/50).The effective rate of the observation group was significantly superior to that of the control group and the routine group,and the difference was statistically significant(P＜0.05).(2)At 6,12,24,48 hours after treatment,the VAS of pain scores of the three groups were significantly improved(P＜0.05),and the improvement of VAS pain score in the observation group was significantly superior to that in the control group and the routine group,the difference was statistically significant(P＜0.05).(3)After treatment,the levels of serum NE,5-HT,CGRP,SP and β-EP in the three groups were significantly improved(P＜0.05),and the levels of serum NE,5-HT,CGRP,SP and β-EP in the observation group were significantly superior to those in the control group and the routine group,the differences were statistically significant(P＜0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with electroacupuncture in the treatment of postoperative pain of hemorrhoids of qi stagnation and blood stasis type can significantly improve the pain symptoms of patients.The levels of serum 5-HT,CGRP,NE,SP and β-EP were significantly improved,and the curative effect was significant.