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.

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.

The interaction between skeletal aging and systemic aging has emerged as a frontier in the field of aging biology research.Recent studies have indicated that bones serve not only as mechanical support organs but also as endocrine organs that regulate systemic homeostasis through bone-derived factors.This review systematically elaborates the characteristics and mechanisms of skeletal aging, including tissue structural remodeling, cellular phenotypic changes, microenvironmental disruption, and molecular network disorders, etc.In aging organisms, bones interact with other organs to form a "bone-system aging axis", thereby promoting the occurrence and development of geriatric comorbidities.Accordingly, multi-target intervention strategies targeting the "bone-system aging axis" show the potential in decelerating the progression of systemic aging.In-depth research on the characteristic changes in inter-organ communication during the aging process of the body is not only conducive to facilitating the development of more comprehensive systemic anti-aging strategies, but also provides a new perspective for treating geriatric comorbidities and achieving healthy aging.

Objective To observe changes of brain functional connectivity in clinical frontline physicians under high occupational stress risk using gradient analysis based on MRI.Methods Totally 25 clinical frontline physicians were prospectively enrolled as observation group,while 25 non-medical staff in hospital taken as controls(control group).Brain resting-state functional MRI were acquired and preprocessed with Brainspace toolbox.Brain functional connectivity gradients were calculated,and the gradient components were compared between groups.Results In hierarchical structures of gradient components 1 and 2,significant increase of gradient components were noticed in observation group,mainly including default mode network,visual network and dorsal attention network related brain regions.Conclusion Gradient components of single modal brain regions in clinical frontline physicians significantly increased under high occupational stress risk.

Objective To discuss the clinical value of preoperative neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in predicting the prognosis of patients with unresectable hepatocellular carcinoma(HCC)after receiving transcatheter arterial chemoembolization(TACE)combined with micro wave ablation(MWA).Methods The clinical data of 110 patients with unresectable HCC,who received TACE with sequential MWA at the Affiliated Hospital of Xuzhou Medical University of China from March 2018 to March 2022,were retrospectively analyzed.The median NLR and PLR values were used as the cut-off values.Mann-Whitney U test was used to compare the differences in the baseline characteristics between the high NLR/PLR group and low NLR/PLR group.Overall survival(OS)and progression-free survival(PFS)curves were plotted by using Kaplan-Meier method,which were compared by using log-rank test.Univariate Cox proportional hazards regression model was adopted to determine the factors associated with OS and PFS.Multivariate analysis of the variables,which had a P＜0.05 in the univariate analysis,was performed.Results The median NLR and PLR were 2.05 and 90 respectively.Compared with the high NLR/PLR group,in the low NLR/PLR group the OS was obviously better[1 100 days(95％CI=1 047.7-1 153.7)vs 683 days(95％CI=552.5-814.8);1 076 days(95％CI=996.4-1 156.2)vs 721 days(95％CI=583.0-859.8)](all P＜0.01),and the PFS was longer[720 days(95％CI=361.6-1 078.4)vs 298 days(95％CI=47.0-205.8);545 days(95％CI=292.3-797.7)vs 270 days(95％CI=213.5-326.5)](all P＜0.05).High NLR(HR=2.193,95％CI=1.358-3.541,P=0.001;HR=37.883,95％CI=4.83-296.760,P=0.001)and high PLR(HR=2.117,95％CI=1.306-3.434,P=0.002;HR=6.547,95％CI=2.367-18.113,P＜0.01)were the predictors of poor PFS and OS.Conclusion The preoperative NLR and PLR have a good predictive value for the therapeutic effect of TACE with sequential MWA for HCC.

Objective To compare the curative efficacy of balloon stent kissing technique and jailed wire technique in treating coronary bifurcation lesions(CBL)in the elderly patients.Methods A total of 104 elderly patients with CBL,who received interventional surgery from January 2023 to December 2023 in the First Hospital of Hebei University and Hebei Provincial Hospital of Traditional Chinese Medicine were enrolled in this study.The patients were divided into balloon stent group(n=51,using balloon stent kissing technique)and jailed wire group(n=53,using jailed wire technique).The postoperative changes in diseased vessels,myocardial and endothelial function injuries were compared between the two groups,and the incidence of postoperative major adverse cardiovascular event(MACE)was calculated.Results Half a year after surgery,in both groups the minimum internal diameters of the arterial main branch and lateral branches were larger than their preoperative values(P＜0.05),and the stenosis ratio of the lesion segment was smaller than the preoperative value(P＜0.05).In balloon stent group,the minimum internal diameter of lateral branches was larger than that in jailed wire group(P＜0.05),and the stenosis ratio of the lesion segment was smaller than that in jailed wire group(P＜0.05).Seven days after surgery,in both groups the levels of serum BNP,hs-cTnI,CK-MB,ET-1 and vWF were lower than their preoperative values,while the level of serum NO was higher than its preoperative value.The changes in the above indicators in balloon stent group were more obvious than in jailed wire group.No statistically significant difference in the incidence of MACE existed between the two groups(x2=1.605,P=0.205).Conclusion In treating elderly patients with CBL,both balloon stent kissing technique and jailed wire technique can improve the stenosis degree of the arterial main branch and lateral branches,but balloon stent kissing technique is superior to jailed wire technique in improving postoperative short-term myocardial function and endothelial function.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such 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 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 value of MULTI-parametric MR imaging with flexible design (MTP) combined with microview diffusion weighted imaging (DWI) in predicting pituitary tumor invasion of cavernous sinus.Methods:This was a cross-sectional study. The clinicopathological and imaging data of 59 patients with suspected pituitary tumor who were admitted to the First Affiliated Hospital of Dalian Medical University from December 2021 to August 2024 were prospectively analyzed. According to Knosp classification, patients with pituitary tumor were divided into non-invasive group (28 cases) and invasive group (31 cases). All patients underwent MTP and microview DWI sequence scanning, and the corresponding parameter values [T 1, R 2*, T 2* and apparent diffusion coefficient (ADC)] were measured on the MTP quantitative map and ADC map at the maximum diameter level of the pituitary tumor. Independent sample t test and Mann-Whitney U test were used to compare the clinical data, quantitative parameter values and proliferation index (Ki-67) between the non-invasive group and the invasive group. Quantitative parameter values with statistically significant differences were jointly included in logistic regression to construct the model. Receiver characteristic curve and area under the curve (AUC) were used to analyze single variables and logistic model in predicting the value invasion of pituitary tumor cavernous sinus invasion. Spearman correlation was used to analyze the correlation between the quantitative values and Ki-67 level. Results:There was no significant difference in age and gender between the non-invasive group and the invasive group ( P>0.05). T 1 and T 2* values in invasion group were higher than those in non-invasion group ( Z=4.42, P<0.001; Z=3.43, P<0.001), R 2* values and ADC values in the invasion group were lower than those in the non-invasion group, and the difference was statistically significant (t=4.07, P<0.001; Z=-3.07, P=0.002). The AUC values of T 1, R 2*, T 2*, ADC, logistic model 1(T 1+R 2*+ADC) and logistic model 2(T 1+T 2*+ADC) for predicting pituitary tumor cavernous sinus invasion were 0.835, 0.767, 0.760, 0.733, 0.926 and 0.925, respectively. Correlation analysis showed that the value of pituitary tumor T 1 was positively correlated with Ki-67 ( r=0.431, P=0.002). Conclusion:Quantitative parameters of MTP sequence and microview DWI sequence can quantitatively evaluate pituitary tumor invasion of cavernous sinus, and the combination of the two sequences can significantly improve the prediction efficiency.