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）］

Colorectal cancer(CRC)is a malignant tumor formed in the colon or rectum,usually caused by uncontrolled growth and division of normal cells in the body.Cell apoptosis,pyroptosis,and necroptosis are key pathways of cell death in colorectal cancer.The comprehensive treatment strategy includes the synergistic effect of cell death inducers with chemotherapy,immunotherapy,and targeted therapy.Traditional Chinese medicine plays an important role as an adjuvant therapy in regulating cell death.The combination of traditional Chinese and western medicine has shown significant effects in precancerous lesions,improving efficacy,reducing adverse reactions,and reducing drug resistance.Although the research on the mechanism of cell death is not yet sufficient,emphasizing the unique characteristics of traditional Chinese medicine,clarifying the anti-tumor mechanism of traditional Chinese medicine,and achieving modern scientific internationalization of integrated traditional Chinese and western medicine treatment for colorectal cancer have become future research directions.This article will comprehensively review the molecular mechanisms of cell apoptosis,pyroptosis,and necroptosis from the perspective of combining traditional Chinese and Western medicine,as well as their regulatory role in the treatment of colorectal cancer.

Colorectal cancer(CRC)is a malignant tumor formed in the colon or rectum,usually caused by uncontrolled growth and division of normal cells in the body.Cell apoptosis,pyroptosis,and necroptosis are key pathways of cell death in colorectal cancer.The comprehensive treatment strategy includes the synergistic effect of cell death inducers with chemotherapy,immunotherapy,and targeted therapy.Traditional Chinese medicine plays an important role as an adjuvant therapy in regulating cell death.The combination of traditional Chinese and western medicine has shown significant effects in precancerous lesions,improving efficacy,reducing adverse reactions,and reducing drug resistance.Although the research on the mechanism of cell death is not yet sufficient,emphasizing the unique characteristics of traditional Chinese medicine,clarifying the anti-tumor mechanism of traditional Chinese medicine,and achieving modern scientific internationalization of integrated traditional Chinese and western medicine treatment for colorectal cancer have become future research directions.This article will comprehensively review the molecular mechanisms of cell apoptosis,pyroptosis,and necroptosis from the perspective of combining traditional Chinese and Western medicine,as well as their regulatory role in the treatment of colorectal cancer.

Objective To explore the role of secreted phosphoprotein 1(SPP1)and myeloid differentiation primary response 88(MYD88)in morphine-induced cardiomyocyte apoptosis.Methods A morphine addiction model was established in Sprague-Dawley(SD)rats.Twelve SD rats were randomly assigned to the normal saline(NS)group or the morphine-dependent(DAM)group.Histopathological analysis was employed to observe and compare myocardial tissue morphology between the two groups.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was performed to assess the number of apoptotic cells in each group.The expression levels of SPP1 and MYD88 were evaluated using immunohistochemistry.Quantitative real-time poly merase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression of SPP1,MYD88,Bax,Bcl2,Caspase-3,and Caspase-9.Simultaneously,Western blot analysis was used to detected the expression of Cleaved Caspase-3 and Cleaved Caspase-9 proteins.In vitro,SPP1 expression was knocked down in primary neonatal rat cardiomyocytes(NRCMs),and cells were divided into three groups:control(CON),morphine treated(DA),and shSPP1#3+DA.Cell viability was assessed using the CCK-8 assay,and apoptosis rates were determined by flow cytometry.Results HE and TUNEL staining of myocardial tissues from morphine-addicted SD rats revealed that,compared with the NS group,myofibrils in the DAM group exhibited partial disruption and a significant increase in apoptotic cells(P<0.05).Western blot and RT-qPCR analyses demonstrated that,relative to the NS group,the mRNA and protein levels of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 were significantly upregulated in the DAM group(P<0.05),whereas Bcl2 expression was significantly downregulated at both mRNA and protein levels(P<0.05),and the protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were also increased.with all differences being statistically significant.In NRCMs following morphine intervention,cell viability in the DA group was markedly reduced compared to the CON group(P<0.05),accompanied by a signifi-cant increase in apoptosis rate(P<0.05).Consistently,Western blot and RT-qPCR results showed elevated mRNA and protein expression of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 in the DA group(P<0.05),along with decreased Bcl2 expression(P<0.05).The protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were elevated simultaneously.In contrast,the shSPP1#3+DA group exhibited opposing trends compared to the DA group,with statistically sig nificant differences(P<0.05).Conclusion SPP1 and MYD88 play critical roles in mediating morphine-induced cardiomyocyte apoptosis,and silencing SPP1 has been shown to significantly reduce the extent of cardiomyocyte apoptosis following morphine exposure.

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

Objective:To compare the treatment time stability, inter- and intra-fraction errors, and clinical target volume (CTV) to planning target volume (PTV) margin expansions under different gated window settings in deep inspiration breath hold (DIBH) radiotherapy for breast cancer, and to analyze the correlation between organ at risk (OAR) dose optimization and changes in lung volume.Methods:A retrospective analysis was conducted on 65 patients with left-sided breast cancer who received DIBH radiotherapy after modified radical mastectomy. CT simulation positioning was performed using 2 mm or 3 mm gated window for DIBH, followed by target delineation, treatment planning, and dose verification. During treatment, setup errors guided by cone beam CT (CBCT), intra-fraction monitoring errors, and treatment times were recorded. The coefficient of variation (CV) of treatment time was calculated for both gated window settings. Based on inter- and intra-fraction error distributions, the expansion distance of the CTV were determined using the van Herk formula. Dosimetric differences between DIBH and free-breathing (FB) plans for the left lung, heart, and left anterior descending coronary artery (LAD) were compared. Spearman correlation analysis was performed between the relative increase in left lung volume and the relative reduction in OAR dose. Paired t-tests were used for inter-group comparisons. Results:The mean CV of the 3 mm gated window group was 0.08±0.03, which was lower than that of the 2 mm group (0.10±0.04; t=-3.91, P<0.001). The setup errors of the 2 mm group in the X, Y, and Z directions were (1.27±1.03), (1.68±0.94), (1.90±1.25) mm, respectively-significantly smaller than those of the 3 mm group [(1.81±1.41), (2.07±1.69), (2.93±1.90) mm; t=-5.80, -2.33, -5.33; P<0.001,=0.014,<0.001). Setup errors for both groups were within the 25%-75% range and all below 5 mm. The intra-fraction deviations of the 2 mm group in the X, Y, and Z directions were (0.54±0.33), (0.79±0.44), (0.70±0.53) mm, respectively, significantly smaller than those of the 3 mm group [(0.62±0.43), (0.93±0.66), (0.87±0.67) mm; t=-3.87, -3.46, -2.71,all P<0.001). The mean intra-fraction errors of both groups were within 1 mm, with greater deviations in the Y and Z directions than those in the X direction. The CTV expansion margins for the 2 mm group in the X, Y, and Z directions were 4.21, 5.35, 5.99 mm, respectively, while those for the 3 mm group were 5.81, 6.89, 9.06 mm. Compared with FB, DIBH significantly reduced the doses to the left lung, heart, and LAD (all P<0.01). The increase in left lung volume was moderately negatively correlated with the reduction in left lung D mean ( r=-0.43, P=0.028), and highly negatively correlated with the dose reductions to the heart and LAD (both P<0.001). Conclusions:The variability in respiratory gated window settings can lead to differences in treatment time stability as well as inter- and intra-fraction errors, consequently affecting CTV-to-PTV margins. The DIBH technique demonstrates significant dosimetric benefits in reducing radiation exposure to the left lung, heart, and LAD. Volumetric expansion of the left lung is strongly and inversely correlated with the reduction in radiation dose to both the heart and LAD.

Objective : To investigate the effects of branched-chain amino acid(BCAA) on the differentiation of 3T3-L1 preadipocytes and its potential mechanism. Methods : 3T3-L1 preadipocytes were divided into the Control, differentiation medium(DM), low-concentration BCAA, and high-concentration BCAA groups. A CCK-8 assay was utilized to evaluate pre-adipocyte survival under various BCAA concentrations. Oil-red O staining was used to observe the formation of lipid droplets in adipocytes. Intracellular triglyceride(TG) and total cholesterol(TC) were detected by enzymatic method. RT-qPCR and Western blot were used to detect the mRNA and protein expression of Stat3 and adipocyte differentiation-related genes. Results : CCK-8 results showed that the viability of 3T3-L1 cells was not affected when the BCAA concentration was ≤ 10 mmol/L. Compared with the DM group, the low-concentration BCAA groups(0.5 and 1.0 mmol/L) had significantly larger intracellular lipid droplets, increased number of lipid droplets, and elevated levels of the intracellular TC(0.88vs0.68 mmol/g; 0.83vs0.68 mmol/g,P<0.01) and TG(0.77vs0.40 mmol/g; 0.62vs0.40 mmol/g,P<0.01). Nevertheless, the cell differentiation in the high-concentration group(5.0 and 10.0 mmol/L) significantly decreased compared with that in the DM group. Further, levels of PPARγ, C/EBPα, Adiponectin, and FABP4 mRNA and protein expression significantly increased in the low-concentration group, but significantly decreased in the high-concentration group than that in the DM group(P<0.01). In addition, low concentrations of BCAA promoted stat3 phosphorylation, while high concentrations inhibited its phosphorylation(P<0.01). Conclusion BCAA have a dual role in regulating the differentiation of preadipocytes through Stat3, i.e. low concentrations of BCAA induce cell differentiation by promoting Stat3 phosphorylation; whereas high concentrations of BCAA inhibit Stat3 phosphorylation and cell differentiation.

Objective To investigate the gene expression profile of cervical exfoliated cells from woman treated by artificial cycle,and their potential association with endometrial receptivity in order to screen specific biomarkers closely related to the receptivity.Methods A total of 19 female patients were enrolled from those preparing for frozen embryo transfer(FET)at the Reproductive Center of First Medical Center of Chinese PLA General Hospital from February 2024 to October 2024.Under the artificial cycle frozen embryo transfer protocol,the endometrial tissues were collected on the 4th day after progesterone administration(P+4)to verify their endometrial receptivity status.Additionally,cervical exfoliated cells were collected on the 4th day(P+4)and the 6th day(P+6)after progesterone administration.RNA sequencing(RNA-Seq)was used to detect gene expression profiles.Differentially expressed genes(DEGs)were identified using the criteria of|log2fold change|＞1 and a false discovery rate(FDR)＜0.05,followed by bioinformatics analysis.The protein-protein interaction(PPI)network of DEGs was constructed using R software(4.4.1)and analyzed with gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analyses.The candidate genes were identified based on the PPI network using Cytoscape software.Quantitative reverse transcription PCR(RT-qPCR)was employed to validate the target candidate genes both in vitro and in vivo.Results The rsERT confirmed that all 19 women were in state of endometrial receptivity at P+6.RNA-Seq identified 3 458 DEGs in cervical exfoliated cells between P+4 and P+6.The up-regulated DEGs were mainly enriched in the pathways associated with immune response and cell differentiation,and the down-regulated ones were mainly enriched in the pathways associated with lipid metabolism and cell proliferation.Using maximal clique Centrality(MCC)algorithm in the PPI network,the top 20 genes were selected.Among them,6 genes,such as IFIT2,OASL,MX1,RSAD2,IFIT1 and IFIT3,tied for the first place,and the 6 genes all belong to interferon-stimulated genes(ISGs).qRT-PCR indicated that the above 6 genes showed significantly higher expression levels in the cervical exfoliated cells at the P+4 stage than the cells at the P+6 stage(P＜0.05).Conclusion There are changes in the expression levels of the genes related to immunity and cytoskeleton remodeling in cervical exfoliated cells during the endometrial receptivity phase.The decrease in the expression of ISGs may serve as a potential biomarker for endometrial receptivity.

Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy (CSF1R-L) is a rare autosomal dominant neurodegenerative disorder caused by mutations in the CSF1R gene. It is typically characterized by rapidly progressive cognitive decline, motor dysfunction, and psychiatric or behavioral abnormalities, leading to significant disability and early mortality. More than 100 mutations of CSF1R have been identified in CSF1R-L, but the clinical-genotype relationship is unclear. This report describes a case of CSF1R-L that initially presented with atypical symptoms of left lower limb pain, numbness, and weakness. Despite the non-specific presentation, comprehensive imaging data were available throughout the disease course. Genetic testing identified a heterozygous missense mutation in exon 18 of the CSF1R gene (c.2508CA, p.Ser836Arg), a novel variant not previously reported in the literature. This case offers valuable insights into the dynamic progression of cranial MRI changes in CSF1R-L, broadens the genetic spectrum of this disease, enhances awareness among clinicians, and provides crucial information for the early diagnosis of this condition.