ObjectiveTo explore the possible mechanism of Jianpi Huazhuo Tiaozhi Granule （健脾化浊调脂颗粒， JHTG） in treating atherosclerosis （AS） based on the regulation of perivascular adipose tissue （PVAT） browning via the phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway. MethodsFifteen SPF male C57BL/6J mice served as control group， while 76 ApoE^-/- mice were first fed a high-fat diet for 16 weeks to establish AS model. After successful modeling， they were randomly divided into model group （n=16）， as well as the browning group， the low-， medium- and high-dose JHTG group， with 15 mice in each group. The browning group was intraperitoneally injected with β3-adrenergic receptor agonist CL 316243 at 1 mg/（kg·d） once daily. The low-， medium- and high-dose JHTG groups were treated with 4.3 g/（kg·d）， 8.6 g/（kg·d）， and 17.2 g/（kg·d） of JHTG by gavage， respectively， while the control group and the model group were given normal saline at 10 ml/（kg·d） by intragastric administration， once daily. All groups received continuous intervention for 4 weeks. The aorta was collected to assess the plaque ratio by gross oil red O staining. HE staining was used to measure the plaque area in cross-sections. Masson staining was employed to detect the proportion of collagen fibers in plaque. Transmission electron microscopy was used to observe the quantity and morphological changes of mitochondria and lipid droplets in adipocytes. The levels of serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were detected， as well as tumor necrosis factor α （TNF-α） and interleukin 6 （IL-6） levels in the PVAT and aorta. The protein levels of adiponectin and leptin in PVAT， and protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated phosphoinositide 3-kinase （p-PI3K）， protein kinase B （AKT）， phosphorylated protein kinase B （p-AKT）， uncoupling protein 1 （UCP1）， peroxisome proliferator-activated receptor γ coactivator 1α （PGC-1α）， and PR domain containing 16 （PRDM16） were measured. The mRNA expression levels of UCP1， PGC-1α and PRDM16 in PVAT were detected. ResultsCompared to the control group， the model group showed increased serum TG， TC， and LDL-C levels and decreased HDL-C level， elevated TNF-α and IL-6 levels in PVAT and aorta， decreased average fluorescence intensity of adiponectin， increased average fluorescence intensity of leptin， reduced p-PI3K/PI3K and p-AKT/AKT values as well as protein levels and mRNA expression levels of UCP1， PGC-1α and PRDM16 （P＜0.01）. The pathological results showed that no significant plaque formation was observed in the aortas of mice in the control group. In the model group， multiple plaques were observed in the aortas， with large numbers of foam cells， cholesterol crystals， and inflammatory cell aggregation in the plaques. Compared to the model group， the browning group and the high-dose JHTG group significantly improved the above indicators and aortic pathological changes （P＜0.05 or P＜0.01）. Three JHTG groups showed a dose-dependent effect in reducing LDL-C level and plaque ratio by gross oil red O staining， elevating the average fluorescence intensity of adiponectin， the p-AKT/AKT value， the protein level of PGC-1α， and the mRNA expression levels of UCP1 and PRDM16 （P＜0.05）. The high-dose JHTG group and the browning group showed similar efficacy in improving the pathology of the aorta. ConclusionJHTG may promote PVAT browning in AS model mice through the PI3K/AKT pathway， improve the endocrine function of PVAT， inhibit aortic inflammation， and thereby ameliorate the formation of AS plaques.

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

Objective To investigate the value of synthetic MRI(syMRI)for evaluating structural changes of brain nuclei and white matter in patients with Parkinson disease(PD).Methods Forty-five PD patients(PD group)and 35 healthy controls(HC group)were prospectively enrolled.Head scanning with strategically acquired gradient echo sequence was performed,then syMRI was obtained with post-processing.The values of T1,proton density(PrD),R2* and magnetic sensitivity values(MSV)of nuclei and white matter were measured based on syMRI and compared between groups.The correlations of syMRI quantitative parameters of nuclei and white matter being significantly different between groups with neurological function scores of subject were analyzed,and a combined model was established using multivariate logistic regression analysis.Receiver operating characteristic(ROC)curve was drawn,the efficacy of single syMRI quantitative parameter and combined model for diagnosing PD was evaluated.Results Compared with HC group,T1 and PrD values of bilateral caudate nuclei decreased,while MSV of bilateral substatia nigra and right red nucleus increased(all FDR correction P＜0.05),while T1 and PrD values of bilateral splenium of corpus callosum,PrD values of left posterior limbs of the internal capsule(PLIC),R2* values of bilateral PLIC and right genu of the corpus callosum decreased in PD group(all FDR correction P＜0.05).syMRI quantitative parameters of the above brain regions were correlated with scores of Montreal cognitive assessment and Hamilton anxiety scale(r=-0.390-0.416,all P＜0.01).The area under the curve of single syMRI quantitative parameter for diagnosing PD was 0.664-0.788,lower than that of combined model(0.905,Z=2.653-4.096,all P＜0.05).Conclusion SyMRI could be used to quantitatively evaluate structural changes of brain nuclei and white matter in PD patients.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective To explore the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound,construct a nomogram for predicting poor postoperative prognosis,and conduct external validation of the nomogram.Methods Clinical data of 451 patients with intestinal obstruction who underwent endoscopic ultrasound transnasal-intestinal obstruction catheterization from February 2019 to February 2022 were collected to establish a nomogram.Then,194 sets of data with the same conditions from February 2022 to February 2024 were collected as the external validation group to validate the model externally.The recovery at 30 d after operation was observed and divided into good prognosis group and poor prognosis group.Multivariate Logistic regression model was used to analyze the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound.Using R 3.6.3 software and the RMS package,a nomogram model for predicting the risk of poor prognosis after intestinal obstruction catheterization under endoscopic ultrasound was constructed..The discrimination and consistency of the model were evaluated using receiver operator characteristic curve(ROC curve)and calibration curve.Results The patients in the poor prognosis group were older than those in the good prognosis group,the levels of C-reactive protein(CRP),procalcitonin(PCT)and neutrophil to lymphocyte ratio(NLR)were higher than those in the good prognosis group,the length of hospital stay was longer than that in the good prognosis group,and the proportion of diabetes,abdominal pain and hormone using were higher than those in the good prognosis group,body mass index(BMI),preoperative albumin level and preoperative nutritional support ratio were lower than those of the good prognosis group,with statistical significance(P<0.05).Multivariate Logistic regression analysis(introduction level was 0.05,exclusion level was 0.107)showed that:age≥68 years(OR＾=2.631,95%CI:1.927～3.593),BMI<22.31 kg/m2(OR＾=2.142,95%CI:1.436～3.195),preoperative albumin<32.47g/L(OR＾=1.962,95%CI:1.506～2.556)and preoperative nutritional non-support(OR＾=2.814,95%CI:1.401～5.654)were independent risk factors affecting the poor prognosis after endoscopic transnasal-intestinal obstruction catheterization(P<0.05).The column nomogram showed that old age,low BMI,low preoperative albumin,and no preoperative nutritional support all increased their corresponding weights.Internal and external validation results indicated good consistency and discrimination of the model.Conclusion age≥68 years,BMI<22.31 kg/m2,preoperative albumin<32.47 g/L,and no preoperative nutritional support are all independent risk factors affecting the ineffective of intestinal obstruction catheterization under endoscopic ultrasound.The nomogram model established in this study based on these four factors has high reliability and practicality.

Objective To investigate the neuroprotective effect of ligustilide(LIG)-mediated phosphatase and tensin homolog(PTEN)-induced putative kinase 1(PINK1)/Parkin pathway on mitophagy in rats with cerebral ischemia-reperfusion injury.Methods 161 male Sprague Dawley(SD)rats were randomly divided into sham operation(Sham)group,model group,LIG low-dose group,LIG high-dose group,mitophagy inhibitor(Mdivi-1)group,LIG high-dose+Mdivi-1 group,and the positive drug Nimodipine(NMDP)group,each with 23 rats.A modified middle cerebral artery wire thrombus method was used to construct a cerebral ischemia/reperfusion model in rats,and the neurobehavioral scores of rats in each group were compared by Longa's five-point scale;the volume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TCC)staining,the histopathology and ultrastructure of the hippocampus were examined by hematoxylin-eosin(HE)staining and transmission electron microscope(TEM).And the Na+-K+-Adenosine Triphosphate was measured by enzyme-linked immunosorbent assay(ELISA);double immunofluorescence staining for translocase of the outer membrane of mitochondrion 20(TOMM20)and Microtubule-associated protein 1 light chain 3(LC3)co-localized area percentage.Flow cytometry assay(FCM)to test the level of reactive oxygen(ROS);real-time fluorescence quantitative PCR(qRT-PCR)was used to measure the relative content of mitochondria in hippocampal neurons;and Western blot was performed to test the level of autophagy and the PINK1/Parkin pathway related protein expression.Results Compared with the Sham group,the neurological function score and cerebral infarction volume of the model group were increased,the hippocampal neurons showed pathological damage such as disordered arrangement,nucleolus disappearance and partial shrinkage of the nucleus and plasma,nuclear membrane rupture,swelling,membrane rupture and crista reduction of some mitochondria,a large number of autophagosomes were observed,and the colocalization area percentage of TOMM20 and LC3 was increased.TOMM20 and cytochrome C oxidase subunit IV isoform 1(COX4I1)in hippocampus and selective autophagy adaptor protein 62(p62)protein expression,mitochondrial encoded ATP synthase 6(mt-ATP6)/Ribosomal protein L13(Rpl13)ratio and Na+-K+-ATPase content decreased,while PINK1 and Parkin protein expression,LC3-II/I ratio and ROS relative content increased,and the differences were statistically significant(t=4.602～52.012,all P<0.01).Compared with the model group,the neurological function score,cerebral infarction volume,pathological and ultrastructural damage of hippocampal neurons were significantly improved in the LIG low,high dose and NMDP groups,and the differences were statistically significant(t=4.851～12.525,all P<0.01).The colocalization of TOMM20 and LC3 and the content of Na+-K+-ATPase were increased,while the expression of TOMM20,COX4I1 and p62 proteins and the mt-ATP6/Rpl13 ratio were decreased in the high-dose LIG group.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were increased,and the differences were statistically significant(t=4.087～33.211,all P<0.01).Compared with the LIG high-dose group,the Mdivi-1 and LIG+Mdivi-1 groups had significantly decreased colocalization of TOMM20 and LC3 and Na+-K+-ATPase content,and significantly increased expression of TOMM20,COX4I1 and p62 proteins and mt-ATP6/Rpl13 ratio.The protein expression of PINK1 and Parkin,LC3-II/I ratio and ROS relative content were decreased,and the differences were statistically significant(t=4.008～43.415,all P<0.01).However,the percentage of TOMM20 and LC3 co-localization area,PINK1 and Parkin protein expression,LC3-II/I ratio and Na+-K+-ATPase content in the hippocampus of the LIG+Mdivi-1 group were higher than those of the Mdivi-1 group.The protein expression of COX4I1 and p62,mt-ATP6/Rpl13 ratio and ROS level were lower than those in MDIV-1 group,and the differences were statistically significant(t=3.721～21.513,all P<0.01).Conclusion LIG may activate mitophagy by regulating PINK1/Parkin signaling pathway to protect neurons from cerebral ischemia-reperfusion injury in rats.

Objective To explore the association between knee torsion and multiple bony abnormali-ties of the lower limb in patients with recurrent patellar dislocation(RPD).Methods The preoperative imaging data of RPD patients treated in our institution between May 2020 and October 2024 were col-lected retrospectively.A total of 238 patients were included in this study,with 83.6%being females.All patients underwent standard hip-knee-ankle CT scans,and lower limb bony structural parameters were reconstructed and measured using Mimics 20.0,focusing on variables such as knee torsion,femo-ral anteversion(FAA),femoral distal torsion angle(DFTA),supratrochlear spur,tibial tuberosity to trochlear groove distance(TT-TG),Caton-Deschamps index,and tibial torsion.Bony abnormalities were categorized based on previously established risk thresholds.Moreover,chi-square tests were em-ployed to compare the composition ratio differences between knee torsion and multiple lower limb osse-ous abnormalities.Results Among all affected knees,the proportion of excessive knee torsion was 33.6%,while in cases with osseous abnormalities,the value was over 40%.Compared with cases of low knee torsion,patients with excessive knee torsion showed significantly higher proportions of FAA(41.3%vs.27.2%,P=0.028),excessive DFTA(60%vs.32.9%,P<0.001),supratrochlear spur(55%vs.38.6%,P=0.016),trochlear dysplasia(93.8%vs.73.4%,P<0.001),excessive TT-TG(68.8%vs.43.7%,P<0.001),and patella alta(50%vs.22.2%,P<0.001).Additionally,95%of knees with excessive torsion exhibited two or more bony risk factors,whereas 55%had four or more bony structural abnormalities,which was significantly higher than those of low knee torsion(55%vs.21.5%,P<0.001).Conclusion In RPD patients,excessive knee torsion is associated with multiple low-er limb bony abnormalities.Moreover,patients with high knee torsion(>12°)are significantly more likely to have multiple bony abnormalities than those with low torsion.Therefore,in surgical decision-making for such patients,lower limb bony abnormalities should be assessed comprehensively.

Objective:To investigate the causal impact of maternal smoking around birth(MSAB)on off-spring's risk of attention deficit hyperactivity disorder(ADHD),autism spectrum disorder(ASD),bipolar disorder(BD),and major depressive disorder(MDD).Methods:The datasets for MSAB and 4 psychiatric disorders were extracted from genome-wide association studies(GWAS).Mendelian randomization(MR)was employed,using in-verse variance weighting(IVW)as the primary analysis method.Sensitivity analyses and outlier correction were conducted using weighted median(WM),MR-Egger regression,and MR-PRESSO.The results were expressed as odds ratios(OR)and corrected for false discovery rate(FDR).Results:MR analysis showed significant causal re-lationships between MSAB and increased risk of ADHD(OR=5.36,95％CI=2.58-7.63,PFDR=0.003),MDD(OR=1.92,95％CI=1.29-2.88,PFDR=0.003),and BD(OR=6.33,95％CI=1.56-8.73,PFDR=0.013).However,no statistically significant association was found between MSAB and ASD(OR=1.66,95％CI=0.23-5.87,PFDR=0.616).Conclusion:This study suggests a potential causal link between maternal smoking around the time of birth and an increased risk of attention deficit hyperactivity disorder,bipolar disorder,and major depressive disorder in offspring.

Objective To explore the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound,construct a nomogram for predicting poor postoperative prognosis,and conduct external validation of the nomogram.Methods Clinical data of 451 patients with intestinal obstruction who underwent endoscopic ultrasound transnasal-intestinal obstruction catheterization from February 2019 to February 2022 were collected to establish a nomogram.Then,194 sets of data with the same conditions from February 2022 to February 2024 were collected as the external validation group to validate the model externally.The recovery at 30 d after operation was observed and divided into good prognosis group and poor prognosis group.Multivariate Logistic regression model was used to analyze the independent risk factors influencing the poor prognosis after transnasal-intestinal obstruction catheterization under endoscopic ultrasound.Using R 3.6.3 software and the RMS package,a nomogram model for predicting the risk of poor prognosis after intestinal obstruction catheterization under endoscopic ultrasound was constructed..The discrimination and consistency of the model were evaluated using receiver operator characteristic curve(ROC curve)and calibration curve.Results The patients in the poor prognosis group were older than those in the good prognosis group,the levels of C-reactive protein(CRP),procalcitonin(PCT)and neutrophil to lymphocyte ratio(NLR)were higher than those in the good prognosis group,the length of hospital stay was longer than that in the good prognosis group,and the proportion of diabetes,abdominal pain and hormone using were higher than those in the good prognosis group,body mass index(BMI),preoperative albumin level and preoperative nutritional support ratio were lower than those of the good prognosis group,with statistical significance(P<0.05).Multivariate Logistic regression analysis(introduction level was 0.05,exclusion level was 0.107)showed that:age≥68 years(OR＾=2.631,95%CI:1.927～3.593),BMI<22.31 kg/m2(OR＾=2.142,95%CI:1.436～3.195),preoperative albumin<32.47g/L(OR＾=1.962,95%CI:1.506～2.556)and preoperative nutritional non-support(OR＾=2.814,95%CI:1.401～5.654)were independent risk factors affecting the poor prognosis after endoscopic transnasal-intestinal obstruction catheterization(P<0.05).The column nomogram showed that old age,low BMI,low preoperative albumin,and no preoperative nutritional support all increased their corresponding weights.Internal and external validation results indicated good consistency and discrimination of the model.Conclusion age≥68 years,BMI<22.31 kg/m2,preoperative albumin<32.47 g/L,and no preoperative nutritional support are all independent risk factors affecting the ineffective of intestinal obstruction catheterization under endoscopic ultrasound.The nomogram model established in this study based on these four factors has high reliability and practicality.

BACKGROUND:Apoptosis plays an important role in secondary brain injury.Therefore,to explore the pathophysiological mechanism of promoting nerve cell survival after traumatic brain injury provides a new direction and theoretical basis for the prevention and treatment of traumatic brain injury. OBJECTIVE:To explore the expression changes of Lnx1 molecule in mammalian cortical neurons after brain injury and the possible mechanism involved in secondary brain injury. METHODS:Eighty adult SD rats were divided into 20 male and 20 female mice in sham operation group and 20 male and 20 female mice in traumatic brain injury group.The traumatic brain injury rat model was established by heavy falling method.At 6,12,24,48,and 72 hours after brain injury,the expression of related molecules in damaged cortical neurons was analyzed by RT-qPCR,western blot assay,and immunofluorescence staining. RESULTS AND CONCLUSION:(1)The brain tissue of traumatic brain injury group was bleeding and obvious tissue injury could be observed.Water content of brain tissue increased after traumatic brain injury.(2)Compared with the sham operation group,the expression of Lnx1 in cortical neurons after traumatic brain injury increased significantly at 24 hours after injury.(3)After traumatic brain injury,the expression of PBK and BCR protein decreased,and the pro-survival factor ctgf increased.(4)These findings suggest that after traumatic brain injury,the expression of Lnx1 is up-regulated in neurons,which may be due to the decrease of the expression of its target molecules PBK and BCR,and further promote the expression of living factor ctgf,which has a protective effect on the damaged neurons.