Objective To investigate the impact of intergenerational caregiving on the brain structure and function of grandparents,and to analyze its correlation with caregiving factors.Methods Healthy adults(66 with grandchildren,24 without grandchildren)were recruited as study subjects,and clinical and MRI data were collected.Resting-state brain functional degree centrality(DC)and surface-based morphometry(SBM)methods were used to compare the differences in brain structure and function between the groups with and without grandchildren.The correlation between the differences in brain regions and △ values with grandchild's age,number,and time spent in childcare were assessed,respectively.Results Compared to the group without grandchildren,the group with grandchildren showed reduced surface area and cortical volume in the left middle temporal gyrus,as well as decreased DC values in the left medial superior frontal gyrus,bilateral orbital superior frontal gyrus,and left anterior cingulate and paracingulate gyrus(P＜0.05),respectively.In the grandchildren group,DC values and △ values in the left orbital superior frontal gyrus,left anterior cingulate and paracingulate gyrus were significantly positively correlated with time spent in childcare.Conclusion The brain structures and functions of grandparents related to empathy and motivation are changed in intergenerational caregiving,which may reveal the neuroplasticity after caring for their grandchildren.

Objective To investigate the effects of Linggui Zhugan Decoction(LGZGD)on left ventricular myocardial fibrosis and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway in rats with chronic heart failure(CHF).Methods A rat model of CHF with myocardial fibrosis was established via coronary artery ligation.Rats were randomly divided into sham-operated,model,LGZGD low/medium/high-dose,and Captopril groups,with 10 rats in each group.After treatment,cardiac function was assessed by echocardiography.Myocardial histopathology was examined using hematoxylin-eosin(HE)staining(with cardiomyocyte cross-sectional area calculated),while collagen deposition was evaluated via Masson's trichrome staining(collagen volume fraction quantified).ELISA was used to measure myocardial TNF-α and IL-6 levels.Western Blot was used to analyze expression of fibrosis markers(TGF-β1,α-SMA,collagen Ⅰ/Ⅲ)and PI3K/AKT pathway components(p-PI3K,p-AKT,p-mTOR).Results Compared with the sham-operated group,the model group showed significantly reduced LVEF and LVFS levels,as well as significantly increased myocardial cell cross-sectional area,collagen deposition area ratio,myocardial tissue TNF-α and IL-6 levels,and TGF-β1,α-SMA,collagen Ⅰ,collagen Ⅲ,p-PI3K,p-AKT,and p-mTOR levels,with statistically significant differences(P＜0.01);compared with the model group,the Captopril group and the medium-and high-dose groups of LGZGD showed significantly increased LVEF and LVFS,as well as significantly increased myocardial cell cross-sectional area,collagen deposition area ratio,TNF-α and IL-6 levels,and TGF-β1,α-SMA,collagen Ⅰ,collagen Ⅲ,p-PI3K,p-AKT,and p-mTOR levels were significantly reduced,with statistically significant differences(P＜0.01);compared with the Captopril group,the high-dose group of LGZGD showed a significant increase in LVEF and LVFS,as well as a significant decrease in myocardial cell cross-sectional area,collagen deposition area ratio,TNF-α,IL-61evels,andTGF-β1,α-SMA,collagen Ⅰ,collagen Ⅲ,p-PI3K,p-AKT,and p-mTOR levels were significantly reduced,with statistically significant differences(P＜0.01).Conclusion LGZGD ameliorates left ventricular myocardial fibrosis and pathological damage in CHF rats,potentially through inhibition of the PI3K/AKT signaling pathway.

Objective:To investigate the interactive effects of loss of the only child and childhood trauma on brain structure, function, and structure-function coupling, and to analyze their association with clinical symptom.Methods:A total of 112 parents who lost their only child and participated in the psychological aid project organized by Local Civil Affairs Department in Sunan aear of Jiangsu Province in China from April 2021 to July 2021 and 36 healthy controls recruited from the community during the same period were selected. Based on childhood trauma questionnaire scores, parents who had lost their only child were divided into those with childhood trauma (group A, n=55) and those without childhood trauma (group B, n=57); similarly, the healthy controls were divided into a group with childhood trauma (group C, n=12) and a group without childhood trauma (group D, n=24). All participants were evaluated by clinical scales such as Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Mini-Mental State Examination (MMSE). MRI 3D-T1 structural images and resting-state functional magnetic resonance imaging data were collected; gray matter volume (GMV) and degree centrality (DC) were calculated by standardized image preprocessing procedure, and ratio of DC to GMV within each voxel was computed to obtain the structure-function coupling map. A two-factor analysis of variance was used to analyze the independent effect and interactive effect of loss of the only child and childhood trauma on GMV, DC, and DC/GMV coupling value. Spearman rank correlation analysis was used to evaluate the associations of above indicators in brain regions with significant difference in independent effect and interactive effect with clinical scale scores. Results:(1) Compared with the participants without childhood trauma (group B+group D), the participants with childhood trauma (group A+group C) showed significantly reduced GMV in the left middle temporal gyrus and right dorsolateral superior frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, Gaussian random field [GRF] corrected). A significant interactive effect of loss of the only child and childhood trauma on GMV in the right precuneus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (2) Compared with the healthy controls, parents who had lost their only child exhibited significantly increased DC in the left middle frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). Compared with participants without childhood trauma, participants with childhood trauma showed significantly increased DC in the right thalamus (voxel-level P<0.01, cluster-level P< 0.05, GRF corrected). A significant interactive effect of loss of the only child and childhood trauma on DC in the left dorsolateral superior frontal gyrus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (3) Compared with the healthy controls, parents who had lost their only child showed significantly decreased DC/GMV coupling value in the left middle frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). Compared with participants without childhood trauma, participants with childhood trauma showed significantly increased DC/GMV coupling value in the right thalamus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). A significant interactive effect of loss of the only child and childhood trauma on DC/GMV coupling value in the left dorsolateral superior frontal gyrus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (4) Correlation analysis revealed that GMV in the right precuneus with significant interactive effect of loss of the only child and childhood trauma was positively correlated with MMSE score ( r s=0.317, P=0.010, Bonferroni corrected). GMV in the left middle temporal gyrus with significant independent effect of childhood trauma was positively correlated with both HAMD score and HAMA score ( r s=0.362, P=0.006; r s= 0.349, P=0.008, Bonferroni corrected). Conclusion:Loss of the only child and childhood trauma can interact to jointly affect the brain structure, function, and structure-function coupling; and some of these brain structure alterations are closely associated with clinical symptoms.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) techniques in assessing symptom remission of post-traumatic stress disorder (PTSD) of bereaved parents who lost their only child.Methods:In this prospective study, 34 parents with PTSD resulting from the loss of the only child were followed-up for 2 years. Based on the PTSD diagnostic status at the end of the follow-up, participants were divided into the remission group and the persistent group.R 3.6.1 and SPSS 20.0 software were used for statistical analysis.Baseline clinical data and neuroimaging findings were compared between the two groups. Logistic regression and LASSO regression analyses were used to identify independent predictors of PTSD symptom remission. The predictive performance of these factors was evaluated by receiver operating characteristic (ROC) curve analysis.Results:Initial screening with univariate Logistic regression and LASSO regression revealed that regional homogeneity (ReHo) in the left middle temporal gyrus, the combined predictive value based on ReHo, and the integrated predictive value combining gray matter volume (GMV) and ReHo (GMV-ReHo predictor) were significant factors influencing symptom remission (all P<0.05). Multivariate Logistic regression further demonstrated that the GMV-ReHo predictor retained independent predictive significance ( P<0.05), with ROC curve analysis showing an area under the curve (AUC) of 0.979 (95% CI=0.935-0.996, P<0.001) for its ability to predict PTSD remission. Notably, a combined model incorporating both the scores of the clinician administered PTSD scale (CAPS) and the GMV-ReHo predictor achieved an enhanced predictive performance, yielding an AUC of 0.984 (95% CI=0.952-0.998, P<0.001). Conclusion:The GMV-ReHo predictor effectively identifies symptom remission in PTSD resulting from the loss of the only child.

Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) techniques in assessing symptom remission of post-traumatic stress disorder (PTSD) of bereaved parents who lost their only child.Methods:In this prospective study, 34 parents with PTSD resulting from the loss of the only child were followed-up for 2 years. Based on the PTSD diagnostic status at the end of the follow-up, participants were divided into the remission group and the persistent group.R 3.6.1 and SPSS 20.0 software were used for statistical analysis.Baseline clinical data and neuroimaging findings were compared between the two groups. Logistic regression and LASSO regression analyses were used to identify independent predictors of PTSD symptom remission. The predictive performance of these factors was evaluated by receiver operating characteristic (ROC) curve analysis.Results:Initial screening with univariate Logistic regression and LASSO regression revealed that regional homogeneity (ReHo) in the left middle temporal gyrus, the combined predictive value based on ReHo, and the integrated predictive value combining gray matter volume (GMV) and ReHo (GMV-ReHo predictor) were significant factors influencing symptom remission (all P<0.05). Multivariate Logistic regression further demonstrated that the GMV-ReHo predictor retained independent predictive significance ( P<0.05), with ROC curve analysis showing an area under the curve (AUC) of 0.979 (95% CI=0.935-0.996, P<0.001) for its ability to predict PTSD remission. Notably, a combined model incorporating both the scores of the clinician administered PTSD scale (CAPS) and the GMV-ReHo predictor achieved an enhanced predictive performance, yielding an AUC of 0.984 (95% CI=0.952-0.998, P<0.001). Conclusion:The GMV-ReHo predictor effectively identifies symptom remission in PTSD resulting from the loss of the only child.

Objective To investigate the impact of intergenerational caregiving on the brain structure and function of grandparents,and to analyze its correlation with caregiving factors.Methods Healthy adults(66 with grandchildren,24 without grandchildren)were recruited as study subjects,and clinical and MRI data were collected.Resting-state brain functional degree centrality(DC)and surface-based morphometry(SBM)methods were used to compare the differences in brain structure and function between the groups with and without grandchildren.The correlation between the differences in brain regions and △ values with grandchild's age,number,and time spent in childcare were assessed,respectively.Results Compared to the group without grandchildren,the group with grandchildren showed reduced surface area and cortical volume in the left middle temporal gyrus,as well as decreased DC values in the left medial superior frontal gyrus,bilateral orbital superior frontal gyrus,and left anterior cingulate and paracingulate gyrus(P＜0.05),respectively.In the grandchildren group,DC values and △ values in the left orbital superior frontal gyrus,left anterior cingulate and paracingulate gyrus were significantly positively correlated with time spent in childcare.Conclusion The brain structures and functions of grandparents related to empathy and motivation are changed in intergenerational caregiving,which may reveal the neuroplasticity after caring for their grandchildren.

Objective:To evaluate the effects and underlying mechanisms of metabolites derived from the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction on the proliferation of multiple myeloma (MM) KM3 cells.Methods:MM KM3 cells in the logarithmic growth phase were treated with 3%, 6%, 9%, or 12% metabolites of kidney-reinforcing, blood circulation-activating, and collateral dredging decoction. Cell viability was assessed using the CCK-8 assay. Apoptosis and necrosis were evaluated using flow cytometry and TUNEL staining. Mitochondrial and cellular ultrastructural changes were examined using transmission electron microscopy. mRNA and protein expression levels of dynamin-related protein 1 (Drp1), mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (MFF), PTEN-induced kinase 1 (Pink1), and E3 ubiquitin ligase (Parkin) were determined through quantitative real-time PCR and western blotting. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with network pharmacology, was utilized for reverse verification of the pharmacodynamic mechanisms and therapeutic targets underlying the anti-MM activity of this decoction.Results:The metabolites of the kidney-reinforcing, blood circulation-activating, and collateral dredging decoction inhibited KM3 cell proliferation and induced apoptosis in a dose-dependent manner. Transmission electron microscopy revealed increased mitochondrial fission and autophagic structures, with effects intensifying at higher metabolite concentrations. mRNA and protein expression of Drp1, Fis1, MFF, Pink1, and Parkin were significantly upregulated in treatment groups compared to controls ( P<0.05), with the most pronounced effects observed in the 12% metabolite group ( P<0.01). HPLC-MS/MS identified 121 bioactive compounds in BHTF, which shared 474 overlapping targets with MM. Enrichment analysis suggested that BHTF exerts antitumor effects primarily through apigenin, palmatine, and other key components by modulating TNF, NF-κB, and mitophagy pathways. Conclusion:The kidney-reinforcing and blood circulation-activating and collateral dredging decoction suppresses the proliferation of MM KM3 cells, potentially through mechanisms involving the regulation of mitochondrial dynamics and induction of autophagy.

Objective:To investigate the interactive effects of loss of the only child and childhood trauma on brain structure, function, and structure-function coupling, and to analyze their association with clinical symptom.Methods:A total of 112 parents who lost their only child and participated in the psychological aid project organized by Local Civil Affairs Department in Sunan aear of Jiangsu Province in China from April 2021 to July 2021 and 36 healthy controls recruited from the community during the same period were selected. Based on childhood trauma questionnaire scores, parents who had lost their only child were divided into those with childhood trauma (group A, n=55) and those without childhood trauma (group B, n=57); similarly, the healthy controls were divided into a group with childhood trauma (group C, n=12) and a group without childhood trauma (group D, n=24). All participants were evaluated by clinical scales such as Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Mini-Mental State Examination (MMSE). MRI 3D-T1 structural images and resting-state functional magnetic resonance imaging data were collected; gray matter volume (GMV) and degree centrality (DC) were calculated by standardized image preprocessing procedure, and ratio of DC to GMV within each voxel was computed to obtain the structure-function coupling map. A two-factor analysis of variance was used to analyze the independent effect and interactive effect of loss of the only child and childhood trauma on GMV, DC, and DC/GMV coupling value. Spearman rank correlation analysis was used to evaluate the associations of above indicators in brain regions with significant difference in independent effect and interactive effect with clinical scale scores. Results:(1) Compared with the participants without childhood trauma (group B+group D), the participants with childhood trauma (group A+group C) showed significantly reduced GMV in the left middle temporal gyrus and right dorsolateral superior frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, Gaussian random field [GRF] corrected). A significant interactive effect of loss of the only child and childhood trauma on GMV in the right precuneus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (2) Compared with the healthy controls, parents who had lost their only child exhibited significantly increased DC in the left middle frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). Compared with participants without childhood trauma, participants with childhood trauma showed significantly increased DC in the right thalamus (voxel-level P<0.01, cluster-level P< 0.05, GRF corrected). A significant interactive effect of loss of the only child and childhood trauma on DC in the left dorsolateral superior frontal gyrus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (3) Compared with the healthy controls, parents who had lost their only child showed significantly decreased DC/GMV coupling value in the left middle frontal gyrus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). Compared with participants without childhood trauma, participants with childhood trauma showed significantly increased DC/GMV coupling value in the right thalamus (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). A significant interactive effect of loss of the only child and childhood trauma on DC/GMV coupling value in the left dorsolateral superior frontal gyrus was observed (voxel-level P<0.01, cluster-level P<0.05, GRF corrected). (4) Correlation analysis revealed that GMV in the right precuneus with significant interactive effect of loss of the only child and childhood trauma was positively correlated with MMSE score ( r s=0.317, P=0.010, Bonferroni corrected). GMV in the left middle temporal gyrus with significant independent effect of childhood trauma was positively correlated with both HAMD score and HAMA score ( r s=0.362, P=0.006; r s= 0.349, P=0.008, Bonferroni corrected). Conclusion:Loss of the only child and childhood trauma can interact to jointly affect the brain structure, function, and structure-function coupling; and some of these brain structure alterations are closely associated with clinical symptoms.

Objective:To investigate the effect of coping style on the gray matter volume in patients with post-traumatic stress disorder (PTSD) who lost their only child, and the mediating role of gray matter volume in evaluating the influence of coping style in clinical symptoms of these parents.Methods:A total of 57 parents with PTSD (PTSD group) and 162 parents without PTSD (non-PTSD group) who lost their only child from September 2016 to March 2017 were enrolled from Jiangsu Province, China. Brain MRI data at resting state were collected. Voxel-based multiple regression analysis was performed to confirm the brain areas in which coping style main effect, diagnosis main effect and their interaction had significant influences in gray matter volumes. Correlations among gray matter volume of brain areas related to coping style, coping style scale scores, and clinician-administered PTSD scale (CAPS) scores were analyzed. Structural equation modeling was used to analyze the mediating role of gray matter volume in the influence of coping style in clinical symptoms of parents lost their only child.Results:(1) The coping style main effect did not significantly influence the gray matter volume in all subjects, and the diagnosis main effect had significant influence in gray matter volume in the right lingual gyrus; their interaction had significant influence in gray matter volume in the right peritalar fissure cortex and lingual gyrus. The positive coping style in the PTSD group had significant influence in the gray matter volumes of the right peritalar fissure cortex and lingual gyrus. (2) In the PTSD group, the scores of positive coping style were positively correlated with the gray matter volumes of the right talus fissure and the lingual gyrus ( P<0.05); the scores of positive coping style, and the gray matter volumes of the right talus fissure and the lingual gyrus were negatively correlated with scores of CAPS-C 5 and CAPS-C ( P<0.05). (3) In the PTSD group, positive coping style can positively predict the gray matter volumes of the right talus fissure and the lingual gyrus; the gray matter volumes of the right talus fissure and the lingual gyrus can negatively predict the avoidance-related symptoms. Conclusion:Positive coping style has influence in the gray matter volumes of the right talar fissure and lingual gyrus of PTSD patients lost their only child; and less positive coping style may affect the brain areas related to visual information processing, thus aggravating avoidance-related symptoms of PTSD patients.