1.Exploring Mechanism of Hei Xiaoyaosan Regulating PI3K/Akt Pathway to Improve Learning and Memory Ability of Insomnia Rats with Liver Depression Syndrome Based on Transcriptomics
Jiamin LIU ; Yale WANG ; Hai HUANG ; Yue LI ; Xin FAN ; Pengpeng LIANG ; Shizhao ZHANG ; Mei YAN ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):114-125
ObjectiveBased on transcriptomics, to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group, model group, eszopiclone group (0.09 mg·kg-1), and low, medium, and high dose groups of Hei Xiaoyaosan (3.82, 7.65, 15.30 g·kg-1), with ten rats in each group. Except for the blank group, the other groups were induced insomnia rat model with liver depression by chronic restraint, tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine (PCPA). Each treatment group received intragastric administration according to the specified dosage, once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test, open field test, and Morris water maze test were used to test the sleep quality, depressive-like behavior, and learning and memory abilities of rats. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nitric oxide (NO) in hippocampus. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of the hippocampal tissue, while terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group, as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting genes. Subsequently, the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to assess the mRNA expression levels of phosphatase and tensin homolog (PTEN), B-cell lymphoma-2 (Bcl-2)-like protein 11 (BCL2L11), and mitogen-activated protein kinase 1 (MAPK1) in hippocampus, and Western blot was employed to evaluate the protein expressions of PI3K, phosphorylation (p)-PI3K, Akt, p-Akt, Bcl-2, Bcl-2-associated X protein (Bax), and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group, the model group exhibited a reduction in body weight, an increase in sleep latency, and a decrease in sleep duration (P<0.01). Additionally, rats showed obvious depression-like behavior, and their learning and memory abilities decreased. Furthermore, the contents of 5-HT, GABA, NO, BDNF and GDNF in hippocampus decreased (P<0.01). Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus, characterized by irregular cell shapes, a reduced cell count, deeply stained and pyknotic nuclei, increased vacuolar degeneration, and an elevated apoptosis rate (P<0.01). Compared with the model group, the body weight of the high and medium dose groups of Hei Xiaoyaosan increased, the sleep latency shortened and the sleep time prolonged (P<0.05, P<0.01). Additionally, depression-like behavior and learning and memory abilities of rats were significantly improved, the levels of 5-HT, GABA, NO, BDNF and GDNF in the hippocampus increased (P<0.05, P<0.01). These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons (P<0.01). Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN, BCL2L11, and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group, the expression levels of PTEN, BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased (P<0.01), while the protein expression levels of p-PI3K, p-Akt and Bcl-2 were decreased (P<0.01), and the protein expression levels of PTEN, Bax and cleaved Caspase-3 were increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN, BCL2L11 and MAPK1 mRNAs (P<0.01), up-regulate the expressions of p-PI3K, p-Akt and Bcl-2 proteins (P<0.01), and down-regulate the protein expressions of PTEN, Bax and cleaved Caspase-3 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN, BCL2L11 and MAPK1, and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.
2.Clinical efficacy of Liwen procedure for obstructive hypertrophic cardiomyopathy: A retrospective study in a single center
Shuai WANG ; Juan TAN ; Hongyan XIAO ; Liang TAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):819-823
Objective To analyze the changes in myocardial injury markers and cardiac function in patients with hypertrophic obstructive cardiomyopathy (HOCM) after Liwen surgery. Methods A retrospective analysis was conducted on the clinical data of HOCM patients who underwent Liwen surgery at the Department of Cardiac Surgery, Wuhan Asia Heart Hospital from December 2019 to April 2023, mainly including preoperative and postoperative dynamic follow-up laboratory test results and echocardiograms. Results A total of 42 patients were included, with 25 males and 17 females, aged (44.76±17.72) years, and a postoperative follow-up time of (15.02±6.97) months. The myocardial troponin level of the patients decreased from preoperative 0.03 (0.02, 0.06) ng/mL to postoperative 0.02 (0.01, 0.05) ng/mL (P=0.006), and the N-terminal pro-brain natriuretic peptide level decreased from preoperative 748.95 (337.40, 1600.75) ng/L to postoperative 367.15 (126.93, 1030.25) ng/L (P<0.001). After surgery, the left atrial diameter of the patients decreased from preoperative (4.18±0.57) cm to postoperative (3.93±0.55) cm (P=0.004), the end-diastolic interventricular septum thickness decreased from preoperative 2.25 (1.90, 2.75) cm to postoperative 1.70 (1.50, 1.90) cm (P<0.001), the left ventricular mass index decreased from preoperative 211.73 (172.28, 261.54) g/m2 to postoperative 156.78 (132.34, 191.36) g/m2 (P<0.001), the left ventricular weight decreased from preoperative 368.89 (292.34, 477.72) g to postoperative 266.62 (224.57, 326.04) g (P<0.001), the end-diastolic posterior wall thickness of the left ventricle decreased from preoperative 1.30 (1.20, 1.60) cm to postoperative 1.20 (1.18, 1.40) cm (P<0.001), the relative wall thickness decreased from preoperative 0.78 (0.78, 1.02) to postoperative 0.63 (0.56, 0.72) (P<0.001), the end-systolic inner diameter of the left ventricle increased from preoperative (2.91±0.50) cm to postoperative (3.19±0.53) cm (P=0.001), and the end-diastolic inner diameter of the left ventricle increased from preoperative (4.41±0.48) cm to postoperative (4.66±0.52) cm (P=0.005). The left ventricular outflow diameter increased from preoperative (1.28±0.46) cm to postoperative (1.57±0.32) cm (P=0.001), the left ventricular outflow pressure gradient decreased from preoperative 58.50 (40.75, 92.50) mm Hg to postoperative 11.50 (7.75, 20.50) mm Hg (P<0.001), the left ventricular ejection fraction increased from preoperative 60.00% (56.75%, 65.00%) to postoperative 63.00% (62.00%, 66.00%) (P=0.024), and the degree of systolic anterior motion of the mitral valve leaflets decreased (P<0.001). Conclusion The cardiac function of patients with HOCM is improved after Liwen surgery, myocardial injury marker levels are decreased, cardiac reverse remodeling occurres, and the surgical outcome is good.
3.Study on the effect and mechanism of Xinyang Tablet on myocardial ferroptosis in mice with chronic heart failure
Jinhua KANG ; Pengpeng LIANG ; Xiaoxiong ZHOU ; Ao LIU ; Zhongqi YANG ; Hongyan WU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):516-528
Objective:
Exploring the effect and mechanism of Xinyang Tablet on reduction of ferroptosis in myocardial cells from mice with chronic heart failure.
Methods:
Sixty C57BL/6J mice were randomly assigned to the sham, model, Xinyang Tablet low-dose (0.34 g/kg), Xinyang Tablet medium-dose (0.68 g/kg), Xinyang Tablet high-dose (1.36 g/kg), and perindopril (0.607 mg/kg) groups using a random number table method (10 mice in each group). Except for the sham group, all other groups underwent aortic arch constriction surgery to construct a chronic heart failure model. On the third day after completion of the modeling, each treatment group was administered the corresponding medication by gavage, while the sham and model groups were administered equal volumes of water by gavage once a day for eight consecutive weeks. After treatment, cardiac ultrasound was used to detect the structure and function of the mouse heart. Hematoxylin and eosin staining was used to detect pathological changes in mouse heart tissue. Masson staining was used to detect the proportion of fibrotic area of mouse heart tissue. Realtime fluorescence PCR was used to detect the mRNA expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen 3α (Col3α), and myosin heavy chain 7 (MYH7) in mouse myocardial tissue. Transmission electron microscope was used to detect the ultrastructure of myocardial cell mitochondria. Reactive oxygen species (ROS) staining was used to detect the mean fluorescence intensity of ROS in myocardial tissue. Micro-determination was used to detect superoxide dismutase (SOD) activity in myocardial tissue. An immunofluorescence assay was used to detect the mean fluorescence intensity of phosphorylated histone deacetylase 2 (p-HDAC2) in myocardial cell. Western blotting was used to detect the protein expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), p-HDAC2, nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and cystine glutamate reverse transporter (xCT) in mouse myocardial tissue.
Results:
Compared to the sham group, the model group showed a decrease in left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), an increase in left ventricular end-systolic diameter(LVESD) and left ventricular end-diastolic diameter (LVEDD), an increase in the proportion of cardiac fibrosis area, an increase in relative expression levels of ANP, BNP, Col3α, and MYH7 mRNA, an increase in ROS mean fluorescence intensity, a decrease in SOD activity, an increase in mean fluorescence intensity of p-HDAC2, an increase in relative expression levels of p-HDAC2 and NOX1 proteins, and a decrease in relative expression levels of Nrf2, GPX4, and xCT proteins (P<0.05). Myocardial fibrosis lesions are obvious, with disordered mitochondrial arrangement, decreased volume and shrinkage, increased membrane density, and reduced mitochondrial cristae. Compared to the model group, the LVEF and LVFS of mice in each dose group of Xinyang Tablet and the perindopril group increased, LVESD and LVEDD decreased, the proportion of fibrotic area of heart tissue decreased, the relative expression levels of ANP, BNP, Col3α, MYH7 mRNA decreased, ROS mean fluorescence intensity decreased, SOD activity increased, mean fluorescence intensity of p-HDAC2 decreased, relative expression levels of p-HDAC2 and NOX1 proteins decreased, and relative expression levels of Nrf2 and xCT proteins increased (P<0.05). Myocardial fibrosis was reduced, the mitochondrial arrangement was more regular, the mitochondria enlarged, the membrane density was reduced, and mitochondrial cristae increased. Compared to the model group, the relative expression level of the GPX4 protein in myocardial tissue increased in the Xinyang Tablet medium-, high-dose, and the perindopril groups (P<0.05).
Conclusion
Xinyang Tablet can improve ferroptosis and ventricular remodeling in mice with chronic heart failure by regulating the HDAC2-mediated Nrf2 antioxidant pathway.
4.Long-chain acylcarnitine deficiency promotes hepatocarcinogenesis.
Kaifeng WANG ; Zhixian LAN ; Heqi ZHOU ; Rong FAN ; Huiyi CHEN ; Hongyan LIANG ; Qiuhong YOU ; Xieer LIANG ; Ge ZENG ; Rui DENG ; Yu LAN ; Sheng SHEN ; Peng CHEN ; Jinlin HOU ; Pengcheng BU ; Jian SUN
Acta Pharmaceutica Sinica B 2025;15(3):1383-1396
Despite therapy with potent antiviral agents, chronic hepatitis B (CHB) patients remain at high risk of hepatocellular carcinoma (HCC). While metabolites have been rediscovered as active drivers of biological processes including carcinogenesis, the specific metabolites modulating HCC risk in CHB patients are largely unknown. Here, we demonstrate that baseline plasma from CHB patients who later developed HCC during follow-up exhibits growth-promoting properties in a case-control design nested within a large-scale, prospective cohort. Metabolomics analysis reveals a reduction in long-chain acylcarnitines (LCACs) in the baseline plasma of patients with HCC development. LCACs preferentially inhibit the proliferation of HCC cells in vitro at a physiological concentration and prevent the occurrence of HCC in vivo without hepatorenal toxicity. Uptake and metabolism of circulating LCACs increase the intracellular level of acetyl coenzyme A, which upregulates histone H3 Lys14 acetylation at the promoter region of KLF6 gene and thereby activates KLF6/p21 pathway. Indeed, blocking LCAC metabolism attenuates the difference in KLF6/p21 expression induced by baseline plasma of HCC/non-HCC patients. The deficiency of circulating LCACs represents a driver of HCC in CHB patients with viral control. These insights provide a promising direction for developing therapeutic strategies to reduce HCC risk further in the antiviral era.
5.A review on the screening methods for the discovery of natural antimicrobial peptides.
Bin YANG ; Hongyan YANG ; Jianlong LIANG ; Jiarou CHEN ; Chunhua WANG ; Yuanyuan WANG ; Jincai WANG ; Wenhui LUO ; Tao DENG ; Jialiang GUO
Journal of Pharmaceutical Analysis 2025;15(1):101046-101046
Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.
6.Characteristics of Basal Sex Hormone Levels and Anti-müllerian Hormone Levels in 1221 Women of Different Ages:A Retrospective Study on the Law of Women Reproductive Aging in the "Seven-year Period" Theory
Wanshi LIANG ; Yiru LIAO ; Jinghan FU ; Luodan HU ; Hongyan YANG ; Jian LIU ; Fangping CHENG ; Guangning NIE
Journal of Traditional Chinese Medicine 2024;65(13):1369-1374
ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine(TCM) through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects, they were divided into the "1
7.Exploring Pharmacodynamic Material Basis and Mechanism of Hei Xiaoyaosan in Improving Learning and Memory Ability of Insomnia Rats Based on UPLC-Q-TOF-MS and Network Pharmacology
Jiamin LIU ; Hai HUANG ; Pengpeng LIANG ; Yale WANG ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(21):19-30
ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology and pharmacodynamics, to investigate the pharmacodynamic material basis and mechanism of Hei Xiaoyaosan in improving learning and memory ability of insomnia rats. MethodUPLC-Q-TOF-MS was used to characterize the chemical constituents of Hei Xiaoyaosan. Network pharmacology was applied to construct the network of active ingredients-intersecting targets-pathways, and molecular docking was performed on key ingredients and core targets. Sixty 8-week-old male SD rats were selected and randomly divided into blank group, model group, Hei Xiaoyaosan low, medium, and high dose groups(3.82, 7.65, 15.30 g·kg-1), and zolpidem tartrate group(0.5 mg·kg-1), with 10 rats in each group. Except for the blank group, the insomnia model was induced by intraperitoneal injection of p-chlorophenylalanine(PCPA) for 4 consecutive days. Rats in each dosing group were administered the corresponding dose by gavage, once a day for 14 consecutive days. Morris water maze test was utilized to assess the learning and memory ability of rats, transmission electron microscopy was employed to examine the ultrastructure of hippocampal synapses, enzyme-linked immunosorbent assay(ELISA) was conducted to analyze the levels of 5-hydroxytryptamine(5-HT), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in hippocampal tissues, and Western blot was performed to detect the expression levels of tumor suppressor protein p53(TP53), rat sarcoma virus(RAS), epidermal growth factor receptor(EGFR), cyclic adenosine monophosphate(cAMP)-response element binding protein(CREB) binding protein(CREBBP), glycogen synthase kinase-3β(GSK-3β), protein kinase B1(Akt1), nitric oxide synthase 1(NOS1), phosphorylated(p)-Akt1, and p-GSK-3β in hippocampal tissues. Additionally, real-time fluorescence quantitative polymerase chain reaction(Real-time PCR) was used to assess the mRNA expression levels of TP53, RAS, EGFR, CREBBP, GSK-3β, Akt1 and NOS1. ResultA total of 176 components were identified in Hei Xiaoyaosan, mainly flavonoids, triterpene saponins, phenylpropanoids and other compounds. Network pharmacological analysis revealed that TP53, V-Ha-Ras Harvey Rat sarcoma viral oncogene homolog(HRAS), neuroblastoma sarcoma viral oncogene homolog(NRAS), EGFR, CREBBP, GSK-3β, Akt1 and NOS1 were the key targets of Hei Xiaoyaosan in treating insomnia. The core targets were predominantly associated with cAMP, RAS, Ras-associated protein 1(Rap1), advanced glycation end products(AGE)/receptor for AGE(RAGE), and EGFR signaling pathways, and the key active ingredients of Hei Xiaoyaosan in treating insomnia were 8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E. Animal experiment results demonstrated that Hei Xiaoyaosan medium and high dose groups significantly increased body weight, shortened sleep latency and prolonged sleep duration in insomnia rats(P<0.01), significantly decreased escape latency and increased platform crossing frequency(P<0.01), and improved the pathological changes of hippocampal synaptic ultrastructure. Meanwhile, the two groups could significantly elevate 5-HT level, Akt1 mRNA expression, Akt1 and p-Akt1 protein expression(P<0.01), reduce inflammatory factor levels(P<0.01), and down-regulate protein expression levels of TP53, RAS, NOS1, EGFR, CREBBP, GSK-3β and p-GSK-3β(P<0.01), as well as mRNA expression levels of TP53, RAS, NOS1, EGFR, CREBBP and GSK-3β in hippocampal tissues(P<0.01). ConclusionThis study determined that the five key active ingredients(8-shogaol, ligustilide F, 6-gingerol, levistilide A and senkyunolide E) in Hei Xiaoyaosan may improve the learning and memory ability of insomnia rats by regulating signaling pathways such as cAMP, RAS, and EGFR, providing an important reference for its mechanism research and clinical application.
8.Short to mid-term results of Chimney Commando in redo valve replacement: A retrospective cohort study
Hongyan LIU ; Bihui HE ; Jing JIN ; Laichun SONG ; Jihui FANG ; Xiang ZHOU ; Yan CHEN ; Liang TAO
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):860-866
Objective To summarize the application of double valve ring enlargement combined with mitral Chimney technique (Chimney Commando) in the secondary valve replacement and to analyze the efficacy in the near and medium term. Methods Patients who underwent the secondary aortic valve and mitral valve (double valve) replacement by Chimney Commando in Wuhan Asia Heart Hospital from 2019 to 2022 were included, and their clinical data were retrospectively collected to analyze the safety and feasibility of this procedure in secondary valve replacement of small aortic root patients. Results A total of 49 patients (44 females and 5 males) were included. The body surface area was 1.64±0.17 m2. The time from the first operation was 13.10±5.90 years. Except for 4 patients whose first operation was valvuloplasty, the remaining 45 patients were all patients after valve replacement, 41 patients of double valves replacement, including 39 patients with mechanical valve and 2 patients with biological valve. The majority of the aortic valves were St.Jude regent 19 mm or St.Jude regent 21 mm, accounting for 30.61% and 34.69%, respectively. The mitral valves were predominantly St.Jude 25 mm mechanical valves, making up 65.31%. All patients underwent Chimney Commando double valve ring enlargement, and the mean time of aortic occlusion was 154.00±45.40 min. The mean size of the aortic valve was 23.90±1.40 mm and that of the mitral valve was 28.20±1.20 mm, and the transvalvular pressure difference across the aortic valve was 20.16±5.76 mm Hg at 6 months postoperatively. There was one death during hospitalization due to multi-organ failure. The follow-up time ranged from 1 to 24 months with a median time of 8 months. Two patients were implanted with permanent pacemakers during the follow-up period and 1 patient died due to massive stroke and malignant arrhythmia. Conclusion Chimney Commando is safe and effective in patients with secondary double valve replacement, and the postoperative prosthetic valves have good hemodynamics, and can achieve good clinical results in the near and medium term.
9.Role and mechanism of intestinal-liver interaction in infectious intestinal/liver injury
Hongyan XIAO ; Huaping LIANG ; Junyu ZHU
Chinese Critical Care Medicine 2024;36(6):656-659
Infection is a common medical problem at present. Different pathogens can lead to different infections. Severe infections can ultimately lead to sepsis, resulting in multiple organ dysfunction and the high mortality of patients. Therefore, studying the occurrence and development of severe infections is essential to improve the survival rate of patients. More and more studies have revealed the important role of connection between intestine and liver in infectious diseases. The maintenance of intestinal mechanical barrier and biological barrier function and the regulation of intestinal flora metabolites can reduce infectious liver injury. Bile acids are important metabolites in the liver, which can inhibit the progression of certain infectious intestinal injuries and promote intestinal damage caused by certain pathogens. In this article, the mechanism of action of the intestinal-liver axis in infection was reviewed to find a new target for the treatment of clinical infection.
10.Correlation between plasma neurofilament light chain and subtypes of Parkinson disease
Xiaojing LIANG ; Hongyan YI ; Tiantian LI ; Fugui XU ; Lijun WANG ; Zhou OU ; Qiang TONG
Chinese Journal of Behavioral Medicine and Brain Science 2024;33(9):783-789
Objective:To investigate the correlation between plasma total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn), neurofilament light chain(NfL) and subtypes of Parkinson disease(PD).Methods:A total of 62 PD patients admitted to the Department of Neurology, the Affiliated Huai 'an No. 1 People 's Hospital of Nanjing Medical University from September 2021 to January 2023 were selected and scored on the Hoehn-Yahr stage(H-Y), unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ), levodopa equivalent daily dosage(LEDD), mini-mental state examination(MMSE), Parkinson disease quality of life questionnaire(PDQ-39) and activities of daily living(ADL). During the same period, 25 healthy individuals matched in age and sex were enrolled as the control group (HC). Clinical characteristics and blood samples were collected. The plasma levels of α-syn, p-α-syn and NfL were detected by enzyme-linked immunosorbent assay(ELISA). PD patients were divided into tremor dominant type (TD, n=27) and akinetic-rigid dominant type (AR, n=35) based on UPDRS-Ⅲ scores. Multifactorial Logistic regression analysis was performed by SPSS 25.0 software to determine the influencing factors of subtypes of Parkinson disease. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off point of plasma NfL between the AR type and the TD type. Results:Plasma α-syn, p-α-syn, NfL levels in the PD group were significantly higher than those of the HC group ( Z=-2.537, -6.580, -7.101, all P<0.05). There were statistically significant differences between the AR type and the TD type in disease duration, H-Y stage, UPDRS-Ⅲ scores, LEDD and MMSE scores ( Z=-2.503, -3.021, -2.025, -2.086, -2.409, all P<0.05). While no significant difference was found in plasma α-syn and p-α-syn levels between the AR type and TD type ( Z=-0.341, -0.085, both P>0.05), the plasma NfL levels were notably higher in the AR type(92.79(16.84, 117.53) pg/mL) compared to the TD type (12.10(6.99, 100.17) pg/mL)( Z=-2.236, P<0.05). Plasma NfL levels were correlated with rigidity scores ( r=0.438, P<0.001), UPDRS-Ⅲ scores ( r=0.337, P<0.05) and motor subtypes ( r=0.286, P<0.05) in PD patients. Multivariate Logistic regression analysis showed that NfL was risk factor for AR( B=0.002, OR=1.002, 95% CI=1.001-1.003, P=0.017). The ROC curve analysis indicated that plasma NfL levels could predict different subtypes of PD with an AUC=0.667, optimal cutoff =26.527. Conclusion:There is a correlation between elevated plasma NfL levels and the occurrence of AR type of PD, suggesting that nerve injury is probably involved in the occurrence and progression of various motor subtypes of PD.


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