ObjectiveTo investigate the effect and mechanism of Banxia Shumitang plus Zhizichi Tang （BZ） on PTEN-induced kinase 1 （PINK1）/Parkin signaling pathway in regulating mitochondrial autophagy in preventing insomnia with depression. MethodsSeventy-two 6-week-old male Kunming mice were randomized into a normal group， a model group， low-dose， medium-dose， and high-dose BZ groups （BZ-L， BZ-M， BZ-H， 2.92， 5.85， 11.7 g·kg^-1）， and an estazolam （0.21 mg·kg^-1） group. Insomnia model was established on days 1 to 3. p-Chlorophenylalanine （PCPA） was injected intraperitoneally at a dose of 400 mg·kg^-1 into mice of the model group and administration groups for 3 consecutive days. Then， the classic depression model was established with chronic unpredictable mild stress （CUMS） for 28 consecutive days. Administration and modeling were performed simultaneously. After gavage， 24 h spontaneous activity test was performed to test sleep state， and sugar preference test and open field test were performed to evaluate anxiety-like state. The morphological changes of the hypothalamus were observed by hematoxylin-eosin （HE） staining， and the number of Nissl bodies was observed by Nissl staining. The ultrastructure of mitochondria was observed by transmission electron microscopy. The mitochondrial membrane potential assay kit （JC-1） was used to examine the mitochondrial function， and a biochemical assay kit was used to measure the ATP content in the hypothalamus. The level of reactive oxygen species （ROS） was determined by the immunofluorescence assay， and the serum levels of 5-hydroxytryptamine （5-HT）， noradrenalin （NE）， and cortisol （CORT） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the expression of PINK1， Parkin， microtubule-associated protein 1 light chain 3 （LC3）， and isolator protein 1 （p62） at protein and mRNA levels， respectively. ResultsThe 24 h spontaneous activity test showed that compared with the normal group， the model group did not exhibit circadian rhythm characteristics in their spontaneous activity time， while the circadian rhythm characteristics were restored in each treatment group （P<0.05）. The sucrose preference test indicated that compared with that in the normal group， the sucrose preference rate in the model group reduced （P<0.01）， and compared with that in the model group， the sucrose preference rate in each treatment group increased （P<0.01）. The open field test revealed that compared with the normal group， the model group exhibited decreased movement distance， average speed， frequency of visits to the central area， and time spent in the central area （P<0.01）， and compared with those in the model group， these parameters in each treatment group increased （P<0.05， P<0.01）. HE staining showed that compared with the normal group， the model group exhibited disarrangement of neurons in the hypothalamus， enlarged intercellular space， and severe nuclear condensation， while the degree of hypothalamic neuronal damage in each treatment group was alleviated. Nissl staining indicated that compared with the normal group， the model group demonstrated aggravated neuronal damage and increased damaged cells （P<0.01）. Compared with that in the model group， the number of damaged cells in each treatment group decreased （P<0.01）. Transmission electron microscopy showed that compared with the normal group， the model group exhibited mitochondrial swelling and rupture in the hypothalamus， with visible autophagic lysosomes in the cytoplasm. Compared with those in the model group， only a few autophagic lysosomes were observed in the BZ-L group， and the degree of mitochondrial swelling and rupture was alleviated in the other treatment groups. ROS immunofluorescence assay showed that compared with the normal group， the model group displayed enhanced red fluorescence intensity of mitochondrial ROS （P<0.01）， which was attenuated in each treatment group （P<0.01）. Mitochondrial membrane potential assay showed that compared with the normal group， the model group had declined mitochondrial membrane potential （P<0.01）， which was recovered in each treatment group （P<0.05， P<0.01）. The biochemical assay of ATP levels indicated that compared with the normal group， the model group exhibited decreased ATP content （P<0.01）， which rebound in each treatment group （P<0.05， P<0.01）. ELISA showed that compared with the normal group， the model group exhibited decreased 5-HT content and increased NE and CORT content （P<0.01）. Compared with the model group， each treatment group showed increased 5-HT content （P<0.01） and reduced NE content （P<0.01） and CORT content （P<0.05， P<0.01）. Western blot of the hypothalamus showed that compared with the normal group， the model group exhibited downregulated protein levels of PINK1， Parkin， and LC3 （P<0.01） and upregulated protein level of p62 （P<0.01）. Compared with the model group， each treatment group showed upregulated protein levels of PINK1， Parkin， and LC3 （P<0.05， P<0.01） and downregulated protein level of p62 （P<0.05， P<0.01）. Real-time PCR showed that compared with the normal group， the model group exhibited downregulated mRNA levels of PINK1， Parkin， and LC3 （P<0.01） and upregulated mRNA level of p62 （P<0.01）. Compared with the model group， each treatment group showed upregulated mRNA levels of PINK1， Parkin， and LC3 （P<0.01） and downregulated mRNA level of p62 （P<0.01）. ConclusionBZ can ameliorate the insomnia and anxiety state of mice by regulating PINK1/Parkin signaling pathway to improve the mitochondrial function， enhance mitochondrial autophagy， protect neurons， and repair damaged nerve cells.

ObjectiveTo investigate the effect and mechanism of Banxia Shumitang plus Zhizichi Tang （BZ） on PTEN-induced kinase 1 （PINK1）/Parkin signaling pathway in regulating mitochondrial autophagy in preventing insomnia with depression. MethodsSeventy-two 6-week-old male Kunming mice were randomized into a normal group， a model group， low-dose， medium-dose， and high-dose BZ groups （BZ-L， BZ-M， BZ-H， 2.92， 5.85， 11.7 g·kg^-1）， and an estazolam （0.21 mg·kg^-1） group. Insomnia model was established on days 1 to 3. p-Chlorophenylalanine （PCPA） was injected intraperitoneally at a dose of 400 mg·kg^-1 into mice of the model group and administration groups for 3 consecutive days. Then， the classic depression model was established with chronic unpredictable mild stress （CUMS） for 28 consecutive days. Administration and modeling were performed simultaneously. After gavage， 24 h spontaneous activity test was performed to test sleep state， and sugar preference test and open field test were performed to evaluate anxiety-like state. The morphological changes of the hypothalamus were observed by hematoxylin-eosin （HE） staining， and the number of Nissl bodies was observed by Nissl staining. The ultrastructure of mitochondria was observed by transmission electron microscopy. The mitochondrial membrane potential assay kit （JC-1） was used to examine the mitochondrial function， and a biochemical assay kit was used to measure the ATP content in the hypothalamus. The level of reactive oxygen species （ROS） was determined by the immunofluorescence assay， and the serum levels of 5-hydroxytryptamine （5-HT）， noradrenalin （NE）， and cortisol （CORT） were determined by enzyme-linked immunosorbent assay （ELISA）. Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR） were employed to determine the expression of PINK1， Parkin， microtubule-associated protein 1 light chain 3 （LC3）， and isolator protein 1 （p62） at protein and mRNA levels， respectively. ResultsThe 24 h spontaneous activity test showed that compared with the normal group， the model group did not exhibit circadian rhythm characteristics in their spontaneous activity time， while the circadian rhythm characteristics were restored in each treatment group （P<0.05）. The sucrose preference test indicated that compared with that in the normal group， the sucrose preference rate in the model group reduced （P<0.01）， and compared with that in the model group， the sucrose preference rate in each treatment group increased （P<0.01）. The open field test revealed that compared with the normal group， the model group exhibited decreased movement distance， average speed， frequency of visits to the central area， and time spent in the central area （P<0.01）， and compared with those in the model group， these parameters in each treatment group increased （P<0.05， P<0.01）. HE staining showed that compared with the normal group， the model group exhibited disarrangement of neurons in the hypothalamus， enlarged intercellular space， and severe nuclear condensation， while the degree of hypothalamic neuronal damage in each treatment group was alleviated. Nissl staining indicated that compared with the normal group， the model group demonstrated aggravated neuronal damage and increased damaged cells （P<0.01）. Compared with that in the model group， the number of damaged cells in each treatment group decreased （P<0.01）. Transmission electron microscopy showed that compared with the normal group， the model group exhibited mitochondrial swelling and rupture in the hypothalamus， with visible autophagic lysosomes in the cytoplasm. Compared with those in the model group， only a few autophagic lysosomes were observed in the BZ-L group， and the degree of mitochondrial swelling and rupture was alleviated in the other treatment groups. ROS immunofluorescence assay showed that compared with the normal group， the model group displayed enhanced red fluorescence intensity of mitochondrial ROS （P<0.01）， which was attenuated in each treatment group （P<0.01）. Mitochondrial membrane potential assay showed that compared with the normal group， the model group had declined mitochondrial membrane potential （P<0.01）， which was recovered in each treatment group （P<0.05， P<0.01）. The biochemical assay of ATP levels indicated that compared with the normal group， the model group exhibited decreased ATP content （P<0.01）， which rebound in each treatment group （P<0.05， P<0.01）. ELISA showed that compared with the normal group， the model group exhibited decreased 5-HT content and increased NE and CORT content （P<0.01）. Compared with the model group， each treatment group showed increased 5-HT content （P<0.01） and reduced NE content （P<0.01） and CORT content （P<0.05， P<0.01）. Western blot of the hypothalamus showed that compared with the normal group， the model group exhibited downregulated protein levels of PINK1， Parkin， and LC3 （P<0.01） and upregulated protein level of p62 （P<0.01）. Compared with the model group， each treatment group showed upregulated protein levels of PINK1， Parkin， and LC3 （P<0.05， P<0.01） and downregulated protein level of p62 （P<0.05， P<0.01）. Real-time PCR showed that compared with the normal group， the model group exhibited downregulated mRNA levels of PINK1， Parkin， and LC3 （P<0.01） and upregulated mRNA level of p62 （P<0.01）. Compared with the model group， each treatment group showed upregulated mRNA levels of PINK1， Parkin， and LC3 （P<0.01） and downregulated mRNA level of p62 （P<0.01）. ConclusionBZ can ameliorate the insomnia and anxiety state of mice by regulating PINK1/Parkin signaling pathway to improve the mitochondrial function， enhance mitochondrial autophagy， protect neurons， and repair damaged nerve cells.

OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.

Objective To explore the changes in trabecular meshwork cell types and cellular communication patterns in primary open-angle glaucoma(POAG).Methods The POAG single-cell dataset GSE135337(including the trabecular meshwork samples of 3 cynomolgus macaque monkeys with POAG and 3 healthy cynomolgus macaque monkeys,data upda-ted to 2023)was downloaded from the Gene Expression Omnibus(GEO),two groups of samplesare named the POAG group and the control group.The downscaling,clustering,grouping,and visualization of data were performed using the Seurat package in R.The cellular communication pattern was analyzed by using the CellChat package in R to identify the differences in the cellular communication pattern between the POAG group and the control group.Meanwhile,the differen-tial gene analysis was performed based on the transcriptome sequencing(RNA-seq)dataset GSE27276(including the atrial horn tissue samples from 17 POAG patients and 19 healthy individuals,data updated to 2023)from the GEO to identify spe-cific cellular communication signaling changes.Results There were no significant differences in the cell types between the control group and the POAG group,including trabecular meshwork cells,macrophages,melanocytes,pericytes,Schlemm's canal cells,myelinating Schwann cells,nonmyelinating Schwann cells,smooth muscle cells,and vascular en-dothelial cells.There was a significant difference in the cellular communication intensity between the POAG group and the control group.The expression of macrophage migration inhibitory factor(MIF)-CD74,C-X3-C motif chemokine ligand 1(CX3CL1)-C-X3-C motif chemokine receptor 1(CX3CR1),and HBB in the POAG group was significantly up-regulated compared with the control group,while the expression of secreted phosphoprotein 1(SPP1)-(ITGA8+ITGB1),SPP1-(IT-GA4+ITGB1),IGF2-IGF2R,CCL8-CCR1,and CCL8/26/24/2-ACKR2 in the POAG group was significantly down-regulated compared with the control group.The RNA-seq analysis results confirmed that the expression levels of HBB,HBD,HBA,and CD74 were higher in the POAG group than in the control group.Conclusion The up-regulation of MIF-CD74 and the down-regulation of SPP1-(ITGA8+ITGB1)and SPP1-(ITGA4+ITGB1)in trabecular meshwork tissues may participate in the fibrotic process,which may be a potential pathogenic mechanism of POAG.

Objective This study aimed to investigate the regulatory effect of electroacupuncture(EA)intervention on the protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)signaling pathway in the hippocampal tissue of Alzheimer's disease(AD)model mice and its effect on astrocytic glycolytic function,further exploring how EA ameliorates AD-related cognitive impairment.Methods Eighteen APP/PS1 mice were randomly divided into model,EA,and sham EA groups(n=6)using the random number table method.Six wild-type C57BL/6J mice served as the control group.The EA group received EA stimulation at acupoints"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)(administered every other day,20 min per session,for 4 weeks).The sham EA group received identical needle insertions at the same acupoints without electrical stimulation.The control and model groups were only restrained.Cognitive function was assessed using the Morris water maze and Y-maze spontaneous alternation tests.Hippocampal morphology was observed via hematoxylin and eosin staining.Hippocampal β-amyloid peptide 1-42(Aβ1-42)deposition was detected using immunohistochemistry.HIF-1α protein expression,the p-Akt/Akt,and p-mTOR/mTOR ratios were measured using Western blotting.Pyruvate kinase M2(PKM2)and lactate dehydrogenase A(LDHA)activities were quantified using enzyme-linked immunosorbent assay.Hexokinase(HK)activity and L-lactate content were determined using a colorimetric assay.Co-localization of LDHA with the astrocyte marker glial fibrillary acidic protein was quantitatively analyzed using immunofluorescence double-labeling combined with Pearson's correlation coefficient.Results Compared with the control group,the model group mice exhibited cognitive decline,as shown by prolonged escape latency(P<0.01),reduced number of platform crossings,lower time spent in the target quadrant,and decreased spontaneous alternation accuracy(P<0.01).The hippocampal neurons showed cell body swelling,deeper nuclear staining,enlarged intercellular spaces,and increased average optical density of Aβ1-42(P<0.01).The p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,were elevated(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels were significantly increased(P<0.01),and the co-localization coefficient of LDHA with astrocytes was enhanced.Compared to the model group,the EA group of mice showed improved cognitive function.The hippocampal neurons had more intact structures,with a more uniform cell distribution.The average optical density of Aβ1-42 decreased(P<0.01),and the p-Akt/Akt and p-mTOR/mTOR ratios,as well as HIF-1α protein expression,decreased(P<0.01).PKM2,LDHA,HK,and L-lactic acid levels decreased(P<0.05),and the co-localization coefficient of LDHA with astrocytes significantly decreased(P<0.01).No significant improvement was observed in any of the indicators in the sham EA group compared with the EA group.Conclusion EA at"Shenshu"(BL23),"Baihui"(GV20),and"Zusanli"(ST36)ameliorates cognitive dysfunction in AD model mice.The underlying mechanism may involve suppressing the overactivation of the hippocampal Akt/mTOR/HIF-1α signaling pathway,thereby downregulating key glycolytic enzyme activities and reducing abnormal lactate accumulation.Furthermore,the astrocytic glycolytic metabolic pathway may constitute a key therapeutic target for this intervention.

OBJECTIVE:To compare the clinical efficacy and radiological results of arthroscopic all-inside technique and traditional technique in anterior cruciate ligament reconstruction.METHODS:Databases such as CNKI,WanFang,VIP,PubMed,Web of Science,Embase,and Cochrane Library were searched for literature on all-inside technique and traditional technique in anterior cruciate ligament reconstruction.The search time was from the establishment of each database to September 2024.Meta-analysis was conducted on the included literature.RESULTS:(1)A total of 17 articles were included in the meta-analysis,with 631 patients in the all-inside technique reconstruction group and 626 patients in the traditional technique reconstruction group.The earliest time for the last follow-up was half a year after surgery,and the latest was 5 years after surgery.Most follow-up period was 2 years.(2)Meta-analysis results showed that compared with traditional anterior cruciate ligament reconstruction,the all-inside technique had a thicker graft during anterior cruciate ligament reconstruction[mean difference(MD)=0.20,95％confidence interval(CI)(0.09,0.31),P=0.000 5],smaller postoperative maximum diameter[standardized mean difference(SMD)=-3.64,95％CI(-6.00,-1.28),P=0.002]and volume[SMD=-3.69,95％CI(-5.37,-2.00),P＜0.000 1]of the tibial tunnel,and higher International Knee Documentation Committee subjective scores[MD=2.41,95％CI(0.49,4.32),P=0.01]and Lysholm scores[MD=1.11,95％CI(0.42,1.8),P=0.002]2 years after surgery.However,the operation time was relatively longer[MD=10.06,95％CI(4.71,15.4),P=0.000 2],and the knee stability was poorer after 2 years[SMD=0.3,95％CI(0.04,0.55),P=0.02].No significant differences were found between the two groups in the following aspects:the subjective scores of the International Knee Documentation Committee at 6 months and 1 year postoperatively[MD=-0.05,95％CI(-1.96,1.83),P=0.96;MD=0.51,95％CI(-1.17,2.19),P=0.55];the difference in anterior laxity of bilateral knees at 1 year postoperatively[SMD=-0.02,95％CI(-0.3,0.27),P=0.9];the Lysholm score at 6 months postoperatively[MD=0.87,95％CI(-0.15,1.89),P=0.09];the objective score of the International Knee Documentation Committee at the last follow-up[RR=0.95,95％CI(0.86,1.06),P=0.37];the American Knee Society Score at the last follow-up[MD=0.33,95％CI(-0.55,1.21),P=0.47];the Tegner score at the last follow-up[MD=0.05,95％CI(-0.11,0.22),P=0.53];the negative rate of the pivot shift test at the last follow-up[RR=0.92,95％CI(0.83,1.01),P=0.09];the postoperative revision rate at the last follow-up[RR=2.2,95％CI(0.98,4.92),P=0.05];and the result of the single-leg hop test at the last follow-up[MD=-0.06,95％CI(-4.99,4.86),P=0.98].CONCLUSION:There were no significant differences in most functional outcome scores and the position of the tibial tunnel between the all-inside technique and the traditional technique after anterior cruciate ligament reconstruction.The all-inside technique was more favorable in terms of subjective International Knee Documentation Committee scores and Lysholm scores at 2 years postoperatively.Meanwhile,the knee joint was more stable 2 years after anterior cruciate ligament reconstruction using the traditional technique.In addition,it was found that the graft was thicker during the all-inside technique,while the diameter and volume of the tibial tunnel were smaller postoperatively,with more bone tissue preserved.Nevertheless,the operation time of the all-inside technique was longer.

Objective:To evaluate the dosimetric characteristics of intensity-modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) in radiation therapy planning for patients with bilateral breast cancer after breast-conserving surgery.Methods:On the computed tomography localization images of 18 patients with bilateral breast cancer, target volumes and organs at risk were contoured to develop both IMPT and VMAT plans for each patient. Two IMPT plans were designed based on the clinical target volume (CTV) with robust optimization (RO-IMPT) and the planning target volume (PTV) without RO (NonRO-IMPT), respectively. The RO-IMPT, NonRO-IMPT, and VMAT plans were normalized such that the prescription dose could cover 95% of the target volume. The dosimetric parameters of target volumes and organs at risk were evaluated, and the dosimetric characteristics of the two techniques were compared.Results:In terms of target volumes, the RO-IMPT group showed significantly lower D1%, Dmean, and homogeneity index (HI) and a significantly higher D99% of the CTV than those of the PTV in the VMAT group ( t=-8.96, -8.21, -8.13, 4.96, P<0.05). The NonRO-IMPT group showed significantly lower D1%, Dmean, and HI and a significantly higher conformity index of the PTV than those of the PTV in the VMAT group ( t=-7.75, -6.25, -6.11, 7.53, P<0.05). In terms of organs at risk, the two IMPT groups showed significantly lower values than the VMAT group for the V5- V30 and Dmean of the whole lungs, V5- V40 and Dmean of the heart, D1% and Dmean of the left anterior descending coronary artery, D1% of the spinal cord, Dmean of normal tissues, and Dmean of the skin ( t= -28.47 to -3.25, P<0.05). There was no significant difference in any other evaluation indices ( P>0.05). Conclusions:Both IMPT and VMAT can meet the clinical requirements of radiotherapy plans following breast-conserving surgery for bilateral breast cancer. IMPT has apparent advantages over VMAT in protecting organs at risk.

Objective:To analyze transcranial sonography（TCS）imaging characteristics of rats with 6-hydroxydopamine hydrochloride（6-OHDA）and explore the correlations between the imaging characteristics with motor deficits and pathological changes.Methods:Twenty-nine male SD rats were divided into 3 groups：8 in the no-treatment control（NC）group，10 in the Sham group and 11 in the 6-OHDA group. The model for Sham/Parkinson's disease（PD）was established by stereotacticly injecting saline/6-OHDA containing ascorbic acid to bilateral substantia nigra pars compacta（SNpc）. After three weeks，the models were stable. At the fourth week and seventh week，the behavioral testing was accomplished. The TCS examination was performed weekly at the same time for four weeks. At the eighth week，the rats were sacrificed for pathology.Results:①Behavioral testing：6-OHDA group showed asymmetric motor deficits and the difference was significant compared with the NC group and Sham group（both P<0.001）. ②TCS examination：compared with the NC and Sham group，there were asymmetric substantia nigra hyperechogenicity（SNH）in 6-OHDA group（both P<0.05）；meanwhile the area of SNH in the left was significantly larger in the right side（ P<0.05）.No significant change in SNH area was found during the continuous observation period of weeks 4-7. For 6-OHDA group，the area of SNH was negatively correlated with the number of forelimb wall-touches（ r=-0.825， P＜0.001）. ③Pathological examination：compared with NC group and sham group，the substantia nigra（SN）of 6-OHDA group showed a series of pathological events，including dopaminergic（DA）neurons asymmetrically decreasing，asymmetric ironion deposition and the number of active microglia increasing（all P＜0.05）. Correlation analysis showed that the area of SNH was negatively correlated with the number of DA neurons survivors（ r=-0.689， P=0.013），while the activation of microglial and the deposition of iron were positively correlated with the area of SNH（ r=0.915，0.735；all P＜0.001）. Conclusions:Asymmetric SNH of 6-OHDA PD rats is a representation of asymmetric motor deficits，and the mechanism is related to a catalogue of asymmetric pathological changes in SN，which comprise DA neurons decreasing，asymmetric iron ions deposition，microglial activating.

Objective:In order to reduce the trauma associated with fetal cardiopulmonary bypass(F-CPB), Our team plans to develop a minimally invasive F-CPB through a small incision in the right axilla. The efficacy of this technique will be verified by using a big experimental animal model, thereby laying the foundation for fetal cardiac surgery supported by F-CPB in the future.Methods:Ten pregnant sheep were divided into F-CPB group(n=5) and control group(n=5). After fasting for 24 h, fetal lambs in the F-CPB group underwent a right axillary incision to establish F-CPB running for 1 h; The control group of fetal lambs only expose heart 1 h without F-CPB. Collect blood sample for laboratory test at the CPB vehicle before(T0), 30 min(T1), and 1 h after F-CPB running(T2) for the F-CPB group and through Superior Vena Cava before(T0), 30 min(T1), and 1 h after F-CPB running(T2) for the control group.Results:The blood routine indicators such as RBC, HCT, and Hb in the F-CPB group of fetal lambs decreased significantly during F-CPB, and their distribution showed significant statistical differences compared with the control group( P<0.05). There were no significant statistical differences in blood gas indicators such as pH, PO 2, PCO 2, and lactate concentration between the F-CPB group and the control group( P>0.05). There was no statistically significant difference in the concentration of cTnI in fetal lamb serum at each time point( P>0.05). There were significant statistical differences( P<0.05) in the distribution of fetal lamb Alb, γ-GGT, CK concentration and cholesterol concentration at various time points in the F-CPB group compared with the control group in liver function examination. In addition, the distribution of BUN in fetal lambs showed a significant difference between the two groups( P=0.006). Conclusion:A minimally invasive F-CPB via small incision in the right axilla is safe and feasible. The experimental animal model has demonstrated that this technique has minimal impact on the vital organ functions and internal environment of fetal lambs, thereby laying the foundation for clinical fetal cardiac surgery in the future.

Objectives:This study aims to explore the relationship between the pericoronary fat attenuation index(FAI)and triglyceride-glucose(TyG)index and atrial fibrillation recurrence after radiofrequency catheter ablation(RFCA)in patients with atrial fibrillation(AF).Methods:This retrospective study enrolled consecutive AF patients who underwent their first successful RFCA at the Affiliated Hospital of Xuzhou Medical University from 2019 to 2023.Pericoronary FAI was quantitatively measured,and the TyG index was calculated.Patients were divided into three groups according to the TyG index quartile:T1 group(TyG index<8.45,n=114);T2 group(8.45≤TyG index≤8.93,n=114);T3 group(TyG index>8.93,n=120).Linear regression was used to analyze the correlation between the TyG index and proximal FAI of three coronary arteries.Logistic regression was employed to explore the correlation between pericoronary FAI,TyG index,and AF recurrence post-RFCA,restrictive cubic splines(RCS)were plotted.Additive interaction and mediation analyses were used to explore the role of pericoronary FAI in the relationship between the TyG index and post-RFCA AF recurrence.Subgroup analysis was performed to explore the predictive value of the TyG index for postoperative recurrence in different patient subgroups.Results:A total of 348 patients were included.After adjusting for confounding factors using linear regression analysis,each unit increase in the TyG index was associated with a 5.389 HU increase in left circumfleex artery(LCX-FAI)(95%CI:3.874-6.904,P<0.001).During one-year follow-up,90 cases(25.86%)experienced AF recurrence.RCS analysis indicated that there was no significant nonlinear relationship between LCX-FAI,TyG index,and AF recurrence after RFCA(Pnon-linear=0.378,Pnon-linear=0.469).The recurrence rate of AF in patients with TyG index>9.08 and LCX-FAI>-83.65 HU was about 57.737 times higher than those with TyG index≤9.08 and LCX-FAI≤-83.65 HU(OR=57.737,95%CI:23.755-155.656,P<0.001).There was an additive interaction between the TyG index and LCX-FAI:relative excess risk due to interaction(RERI)was 50.901(95%CI:0.215-101.587),attributable proportion due to interaction(AP)was 0.882(95%CI:0.769-0.994),and the synergy index(S)was 9.713(95%CI:3.380-27.910).Mediation analysis indicated that LCX-FAI mediated 22%of the relationship between the TyG index and AF recurrence.Subgroup analysis revealed no multiplicative interaction between the type of atrial fibrillation and the TyG index in terms of AF recurrence risk(Pinteraction=0.562).Conclusions:In patients with atrial fibrillation,the TyG index is positively correlated with LCX-FAI,patients with TyG index>9.08 and LCX-FAI>-83.65 HU have significantly increased risk of AF recurrence after RFCA.LCX-FAI partially mediates the relationship between the TyG index and post-RFCA recurrence.Furthermore,the TyG index can effectively predict AF recurrence in both persistent and paroxysmal atrial fibrillation patients.