Parkinson’s disease (PD) is a common neurodegenerative disorder with profound impact on patients’ quality of life and long-term health, and early detection and intervention are particularly critical. In recent years, the search for precise and reliable biomarkers has become one of the key strategies to effectively address the clinical challenges of PD. In this paper, we systematically evaluated potential biomarkers, including proteins, metabolites, epigenetic markers, and exosomes, in the peripheral blood of PD patients. Protein markers are one of the main directions of biomarker research in PD. In particular, α‑synuclein and its phosphorylated form play a key role in the pathological process of PD. It has been shown that aggregation of α-synuclein may be associated with pathologic protein deposition in PD and may be a potential marker for early diagnosis of PD. In terms of metabolites, uric acid, as a metabolite, plays an important role in oxidative stress and neuroprotection in PD. It has been found that changes in uric acid levels may be associated with the onset and progression of PD, showing its potential as an early diagnostic marker. Epigenetic markers, such as DNA methylation modifications and miRNAs, have also attracted much attention in Parkinson’s disease research. Changes in these markers may affect the expression of PD-related genes and have an important impact on the onset and progression of the disease, providing new research perspectives for the early diagnosis of PD. In addition, exosomes, as a potential biomarker carrier for PD, are able to carry a variety of biomolecules involved in intercellular communication and pathological regulation. Studies have shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide a new breakthrough for early diagnosis. It has been shown that exosomes may play an important role in the pathogenesis of PD, and their detection in blood may provide new breakthroughs in early diagnosis. In summary, through in-depth evaluation of biomarkers in the peripheral blood of PD patients, this paper demonstrates the important potential of these markers in the early diagnosis of PD and in the study of pathological mechanisms. Future studies will continue to explore the clinical application value of these biomarkers to promote the early detection of PD and individualized treatment strategies.

ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma， and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography（HPLC） was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces， and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside， chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics， the contents and quantity ratio relationships of the glycosides， aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed， and the partial least squares-discriminant analysis（PLS-DA） and cluster analysis of the main components in different steaming times were conducted， the statistically significant differential markers were selected with the variable importance in the projection（VIP） value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma， there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times， the anthraquinone glycosides and aglycones could be roughly divided into three stages， including rapid change stage， fluctuation change stage and stable stage， and the total amount of tannins showed a decreasing trend. However， the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes， while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening， it was found that chrysophanol， emodin， chrysophanol-8-O-β-D-glucoside， rhein， physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb， which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.

Aim To investigate the protective effect of eriodictyol(ERD)on kidney damage in hypertensive mice and its possible mechanism.Methods Thirty C57BL/6J mice were randomly divided into five groups of six in each group.They were the control group(Ctrl),the hypertension model group(DOCA/Salt),the eriodictyol low-dose(DOCA/Salt+ERD-L),the high-dose(DOCA/Salt+ERD-H)and the positive drug perindopril group(DOCA/Salt+Perindopril).The classic hypertension model was induced by DOCA/Salt,and ERD was administered continuously for four weeks,and blood pressure,serum urea nitrogen,cre-atinine and other indicators were measured.Hematoxy-lin-eosin staining(HE)and Masson staining were used to observe the pathological changes of the kidney.Western blot was used to detect the expression of EMT marker proteins α-SMA,Vimentin,E-cadherin and FN in renal epithelial mesenchymal transition.Real-Time PCR was used to detect the expression of renal inflammatory cytokines Nlrp3,TNF-α,IL-1 β,IL-18,MCP-1 and NADPH oxidase(NOXs).Western blot was employed to detect the expression levels of TGF-β1,phosphorylated(p)-Smad2,TLR4 and NF-κB p65 proteins in mice.Results ERD intervention could delay the occurrence of hypertension,improve the pathological damage of renal tissue,reduce renal collagen deposition.It could also reduce the level of renal inflammation and oxidative stress,improve the level of EMT protein,and significantly reduce the pro-tein expression of TGF-β1,p-Smad2,TLR4 and NF-κB p65.Conclusions ERD is shown to have a signif-icant protective effect on DOCA/Salt hypertensive renal damage,and its mechanism may be related to the regu-lation of TGF-β1/Smad2,TLR4/NF-κB p65 and other signaling pathways.

Aim To study the regulatory effect of poly-datin on D-galactose-induced aging model mice.Methods Fifty-six ICR mice(half male and half fe-male)were divided into normal group,model group,positive group,low,medium and high polydatin treat-ment groups.Aging model was established by subcuta-neous injection of D-galactose(500 mg·kg-1)into the back of neck every day.During the modeling peri-od,the positive group was given donepezil hydrochlo-ride tablets(0.75 mg·kg-1)by gavage,the treat-ment group was given polydatin(40,70,100 mg·kg1)by gavage,and the normal group was given the same amount of normal saline.The learning and cogni-tive ability of mice was evaluated by nesting experi-ment,new object recognition experiment and Morris water maze experiment.The heart,liver,spleen,kid-ney and thymus of mice were taken to calculate the or-gan index.The pathological changes of whole brain tis-sue in mice were observed by hematoxylin-eosin(HE)staining.The levels of T-SOD,MDA,GSH-Px and AchE in serum and whole brain tissue of mice were de-tected by ELISA.The protein expression levels of Keap1,Nrf2 and HO-1 in hippocampus of mice were detected by Western blot.Results Compared with the model group,the nesting ability,the ability to recog-nize new objects and the ability to find platforms under-water of the mice in the positive group and the low,medium and high dose groups of polydatin were im-proved.The organ index increased.The neuronal dam-age in the cerebral cortex and hippocampus was signifi-cantly ameliorated.The activities of T-SOD and GSH-Px in serum and brain tissue increased and the activi-ties of MDA and AchE decreased.The expression lev-els of Nrf2 and HO-1 protein in hippocampus in-creased,and the expression level of Keap1 protein de-creased.Conclusions Polydatin can ameliorate the learning and cognitive impairment in D-galactose-in-duced aging model mice,and its mechanism may be related to the Keap1/Nrf2/HO-1 pathway.

Aim To explore the potential genes and mechanism of alisol B in the treatment of non-small cell lung cancer(NSCLC).Methods The proliferation and migration of NSCLC cells were detected by CCK-8 and Transwell.Genes of NSCLC and alisol B were col-lected through TCGA and compound gene prediction database,and their intersection genes were obtained.The network of protein-protein interaction(PPI)was constructed by using String database,and the top 20 key nodes were screened out,and the prognosis-related proteins related to the prognosis of NSCLC were screened out by using R language,and the intersection of them was obtained.The potential mechanism of ali-sol B on NSCLC was explored by KEGG and GO en-richment analysis and the relationship between related genes and immune cells,which was verified by cell-lev-el experiments.Results Alisol B inhibited the cell activity and migration ability of NSCLC cells.Five im-portant genes were identified by network pharmacologi-cal analysis:CCNE1,CDK1,COL1A1,COL1A2 and COL3A1.The results of cell experiment showed that al-isol B down-regulated the expression of Cyclin E1,CDK1 and COL1A2 in NSCLC cells.In addition,alisol B could inhibit the expression of COL1A2 and M2 macrophage marker CD206 in macrophages.Conclu-sions Alisol B may inhibit the proliferation of tumor cells by down-regulating CDK1 and Cyclin E1,and may affect the function of macrophages by inhibiting COL1A2,thus regulating the tumor immune microenvi-ronment and inhibiting NSCLC.

Objective To investigate the clinical efficacy of oblique lumbar interbody fusion(OLIF)combined with poste-rior percutaneous internal fixation in patients with lumbar spinal stenosis with or without redundant nerve roots(RNRs).Meth-ods A retrospective analysis of 92 patients with lumbar spinal stenosis treated by oblique lateral lumbar interbody fusion com-bined with posterior percutaneous internal fixation from June 2019 to June 2022 was performed.There were 32 males and 60 females,aged from 44 to 82 years old with an average of(63.67±9.93)years old.All patients were divided into RNRs positive group and RNRs negative group according to redundancy or not before operation.There were 38 patients in RNRs positive group,including 15 males and 23 females.The age ranged from 45 to 82 years old with an average of(65.45±10.37)years old.The disease duration was 24.00(12.00,72.00)months.There were 54 patients in RNRs negative group,including 17 males and 37 females.The age ranged from 44 to 77 years old with an average of(62.42±9.51)years old.The disease duration was 13.50(9.00,36.00)months.The general data of patients were recorded,including operation time,intraoperative blood loss and complications.The imaging parameters before and after operation were observed,including the number of stenosis segments,intervertebral space height,lumbar lordosis angle and dural sac area.The visual analogue scale(VAS)was used to evaluate the back and lower extremity pain,and the Oswestry disability index(ODI)was used to evaluate the activities of daily living.Results All patients were followed up for 8 to 18 months with an average of(11.04±3.61)months,and no complications were found during the follow-up period.The number of stenosis segments in RNRs positive group(1.71±0.46)was more than that in RNRs negative group(1.17±0.38).In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,ODI score were(1.11±0.19)cm,(0.46±0.17)cm2,(5.39±1.00)scores,(5.05±1.01)points,(55.74±4.05)points,respectively.RNRs negative groups respectively(0.97±0.23)cm,(0.69±0.26)cm2,(4.50±0.77)scores,(4.00±0.58)scores,(47.33±3.43)％.In RNRs positive group,intervertebral space height,dural sac area,low back pain VAS,leg pain VAS,ODI score were(1.60±0.19)cm,(0.74±0.36)cm2,(3.39±0.72)scores,(3.05±1.01)scores,(46.74±4.82)scores,respectively.RNRs negative groups respectively(1.48±0.25)cm,(1.12±0.35)cm2,(3.00±0.82)scores,(3.00±0.82)scores,(37.67±3.58)％.The postoperative intervertebral space height,dural sac area,low back pain VAS score,lower extremity pain VAS and ODI score of the patients in the RNRs positive group and the negative group were signifi-cantly improved compared with those before operation,and the differences were statistically significant(P＜0.05).There were statistically significant differences in the number of stenosed segments,preoperative intervertebral space height,dural sac area,low back pain VAS,lower extremity pain VAS,and ODI between the two groups(P＜0.05).There were significant differences in postoperative intervertebral space height and postoperative ODI between the two groups(P＜0.05),but there was no significant difference in intervertebral space height before and after operation and ODI score before and after operation(P＞0.05).There were significant differences in operation time,intraoperative blood loss,postoperative dural sac area,difference of dural sac area before and after operation,postoperative low back pain VAS,difference of low back pain VAS score before and after oper-ation,difference of lower extremity pain VAS before and after operation between the two groups(P＜0.05).Conclusion OLIF combined with posterior percutaneous internal fixation has a good effect on patients with or without RNRs.Multi-segmental lumbar spinal stenosis and decreased dural sac area may lead to the occurrence of RNRs,and LSS patients with RNRs have more severe symptoms.LSS patients with RNRs have worse surgical outcomes than those without RNRs.

Objective:To investigate the clinical characteristics and influence of co-mutated gene on acute myeloid leukemia patients(AML)with FMS-like tyrosine kinase-3(FLT3)mutations.Methods:A total of 273 FLT3+AML patients were enrolled,and the co-mutation gene data of the patients were collected to further analyze the prognosis of the patients.FLT3 and other common mutations were quantified by PCR amplification products direct sequencing and second-generation sequencing(NGS).Results:When patients were divided into FLT3 ITD+,FLT3 TKD+,FLT3 ITD++TKD+and FLT3 ITD-+TKD-group according to the type of FLT3 mutations,it was found that the frequencies of TET2,GATA2,NRAS and ASXL1 mutation were significantly different among the 4 groups(all P＜0.05).When patients were divided into allelic ratio(AR)≥0.5 and＜0.5 group,it was found that the frequencies of FLT3 ITD+,FLT3 ITD-+TKD-,NPM1,NRAS and C-kit were significantly different between the two groups(all P＜0.05).When patients were divided into normal and abnormal karyotype group,it was found that the frequencies of FLT3 ITD+,FLT3 TKD+,NPM1,GATA2 and C-kit were significantly different between the two groups(all P＜0.05).The median overall survival(OS)of AML patients with FLT3 TKD+(including FLT3 ITD++TKD+)was longer than that of patients with FLT3 ITD+alone(P＜0.05).The OS and relapse-free survival(RFS)of AML patients with FLT3++TET2+were both shorter than those of patients with FLT3++TET2-(both P＜0.05).Conclusion:The mutation frequencies of co-mutated genes are correlated with subtypes of FLT3,karyotype and AR.AML patients with FLT3 TKD+have longer OS than patients with FLT3 ITD+alone,and patients with co-mutation of TET2 have shorter median OS and RFS.

Objective:To explore the impact of parenting style on social anxiety among college students, and examine the mediating effect of core self-evaluation.Methods:From November 2022 to January 2023, a total of 1 126 college students in Harbin were taken as research subjects.Interaction anxiousness scale(IAS), short-egna minnen betraffende upfostran-Chinese(s-EMBU-C) and core self-evaluations scale(CSES) were used for analysis. Data were analyzed using SPSS 26.0 software for correlation analysis and analysis of variance.AMOS 27.0 software was used for mediation effect test.Results:Social anxiety (42.31±8.23) was negatively correlated with positive parenting style (5.44±1.45) ( r=-0.072, P<0.05) and core self-evaluation (32.12±6.01) ( r=-0.350, P<0.01), while positively correlated with negative parenting style (7.40±1.74)( r=0.302, P<0.01). Core self-evaluation was positively correlated with positive parenting style ( r=0.362, P<0.01) and negatively correlated with negative parenting style ( r=-0.346, P<0.01).Parent parenting styles had a significant mean direct effect on social anxiety of college students ( βpositive=0.098, βnegtive=0.222).Mediation analyses indicated that core self-evaluation played a masking role between positive parenting styles and social anxiety, with an absolute value of 90.82% for the ratio of indirect(-0.089) to direct effects(0.098).Core self-evaluation had partial mediating effect on negative parenting styles, with direct effect and indirect effect accounting for 73.03% and 26.97% of the total effect, respectively. Conclusion:Parenting style can either directly affect college students' social anxiety or indirectly through the mediating effect of core self-evaluations, with core self-evaluations playing a masking role in the positive parenting styles pathway.

Objective To report single-center experience on CBA combined with LAAC in treat-ment of AF.Methods A retrospective study was conducted on 27 AF patients undergoing one-stop surgery of CBA combined with LAAC in Department of Cardiovascular Diseases of the People's Hospital of Liaoning Provincie from August 2020 to November 2022.The efficacy and safety of the surgery were analyzed.Results There were 22 patients(81.5％)with LAmbre and 5 patients with Watchman(18.5％,including one case of 24 mm Watchman FLX).All the patients achieved complete pulmonary vein isolation,and conversion to sinus rhythm during operation.During a mean follow-up of 30.0±9.2 months,24 patients(88.9％)maintained sinus rhythm at 12-month follow-up,and 22 patients(81.5％)maintained sinus rhythm at 24-month follow-up.TEE at 3 months after operation displayed that all the devices were in good positions and no PDL or DRT was observed.In the 11 patients undergoing cardiac enhanced CT in 12-36 months after surgery,PDL was detected in one patient(9.1％),and uncomplete endothelialisation of the device was observed in another one(9.1％)using the Watchman device.TEE at 26 months revealed one patient(3.7％)of DRT.Conclusion One-stop surgery of CBA combined with LAAC is a feasible treatment option for patients with NVAF and at high risk of stroke.

Objective:To explore the potential action mechanism of Huotu Jiji Pellets(HJP)in the treatment of erectile dys-function(ED)based on network pharmacology and molecular docking.Methods:We identified the main effective compounds and active molecular targets of HJP from the database of Traditional Chinese Medicine Systems Pharmacology(TCMSP)and Integrative Pharmacology-Based Research Platform of Traditional Chinese Medicine(TCMIP)and the therapeutic target genes of ED from the data-bases of Genecards.Then we obtained the common targets of HJP and ED using the Venny software,constructed a protein-protein in-teraction(PPI)network of HJP acting on ED,and screened out the core targets with the Cytoscape software.Lastly we performed GO functional enrichment and KEGG pathway enrichment analyses of the core targets followed by molecular docking of HJP and the core targets using Chem3D and AutoDock Tools and QuickVina-W software.Results:A total of 64 effective compounds,822 drug-related targets,1 783 disease-related targets and 320 common targets were obtained in this study.PPI network analysis showed that the core targets of HJP for ED included ESR1,HSP90AA1,SRC,and STAT3.GO functional enrichment analysis indicated the involvement of the core targets in such biological processes as response to xenobiotic stimulus,positive regulation of kinase activity,and positive regu-lation of MAPK cascade.KEGG pathway enrichment analysis suggested that PI3K-Akt,apoptosis,MAPK,HIF-1,VEGF,autophagy and other signaling pathways may be related to the mechanism of HJP acting on ED.Molecular docking prediction exhibited a good doc-king activity of the key active molecules of HJP with the core targets.Conclusion:This study showed that HJP acted on ED through multi-components,multi-targets and multi-pathways,which has provided some evidence and reference for the clinical treatment and subsequent studies of the disease.