The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.
Humans ; Parkinson Disease/metabolism* ; alpha-Synuclein/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Genetic Predisposition to Disease ; Protein Kinases/genetics* ; Animals ; Glucosylceramidase/genetics* ; Ubiquitin-Protein Ligases/genetics*

The Medical Cases of WU Jutong （《吴鞠通医案》） proposes the principle of "treating all Bi （痹） diseases through taiyin"， which forms the basis for analyzing WU Jutong's understanding of the causes， mechanisms， and treatments of Bi （痹） diseases， providing a reference for clinical diagnosis and treatment. Through an interpretation of the phrase "treating all Bi （痹） diseases through taiyin"， it is suggested that Bi （痹） diseases is primarily caused by dampness， necessitating a focus on spleen and lung in treatment. WU emphasized four main causes of Bi （痹） diseases （wind， cold， dampness， and heat）， with dampness being the predominant factor. The disease location is initially in lung， for which external dampness invades lung first， and internal dampness obstructs the source of water metabolism， impeding lung qi and qi failing to disperse， then dampness further accumulates in the joints， leading to Bi （痹） diseases. WU Jutong proposed the modified Mufangji Decoction （木防己汤） as the foundational prescription for treating Bi （痹） diseases. By comparing the similarities and differences between the modified and original Mufangji Decoction， and analyzing the adjustments in herbal prescriptions， the clinical characteristic of "treating all Bi （痹） diseases through taiyin" is further substantiated.

Objective:To establish criteria for diagnosing lymph node metastasis (LNM) in newly diagnosed papillary thyroid cancer (PTC) patients based on 18F-FDG PET/MR and evaluate its diagnostic efficiency. Methods:The data of 14 patients with PTC (all females, age (38.8±13.5) years) who underwent 18F-FDG PET/MR and ultrasound sequentially 2 weeks before surgery at the First Affiliated Hospital of the Air Force Medical University from May 2021 to August 2023 were retrospectively analyzed. Visual and semi-quantitative assessments were performed on all patients step by step (Ⅱ-Ⅵ area) and neck by neck (left, right, and central area). The dimensions of all suspected lymph nodes were measured on T 2 weighted imaging (WI)-MRI and SUV max was measured on PET. Taking postoperative pathology as the reference standard, the independent risk factors for predicting LNM were determined by multivariate logistic regression analysis, and the diagnostic efficiency of each model was evaluated by ROC curve analysis. Results:A total of 21 macroscopic regions of lymph nodes(15 were malignant, 6 were benign) and 178 lymph nodes (120 were malignant, 58 were benign) were cleared by surgery. Multivariate logistic regression analysis showed that SUV max (odds ratio ( OR)=1.865, 95% CI: 1.323-2.630, P<0.001) and short diameter on MRI (SD-MRI) ( OR=1.752, 95% CI: 1.189-2.580, P=0.005) were independent predictors of LNM. The cut-off value of SD-MRI in predicting LNM was 5.7mm (AUC=0.812, Youden index (YI)=0.463). For the SD-MRI cut-off values ≥5.7 or <5.7mm, the corresponding SUV max cut-off values were 1.6 and 1.8, respectively. When " dual threshold" quantitative criteria (SD-MRI≥5.7mm + SUV max≥1.6 or SD-MRI<5.7mm + SUV max≥1.8) was used as the diagnostic criteria of 18F-FDG PET/MR, the AUC and YI could be improved to 0.909 and 0.818. Based on the regional level analysis, sensitivity, specificity, and accuracy of LNM diagnosis by ultrasound, MRI, and 18F-FDG PET/MR " dual threshold" criteria were 11/15 vs 12/15 vs 13/15, 5/6 vs 3/6 vs 5/6, 76.2%(16/21) vs 71.4%(15/21) vs 85.7%(18/21), respectively. Conclusion:Compared with the ultrasound and MRI, the 18F-FDG PET/MR " dual threshold" criteria exhibits higher sensitivity and accuracy in determining the scope of LNM clearance for PTC patients.

AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

AIM To investigate the protective effects of Shuangyi Qushi Tongluo Capsules(Shuangyi Capsules)on Dexamethasone(Dex)induced osteoporosis in mice.METHODS The C57BL/6J mice were randomly divided into the control group,the model group,the Xianling Gubao Capsules group(1.5 g/kg),and the low-dose,moderate-dose,and high-dose Shuangyi Capsules groups(0.6,1.2,and 2.4 g/kg).The mouse model of osteoporosis was induced by 8-week intraperitoneal injection of Dex sodium phosphate injection(5 mg/kg).The mice had their femur osteogenesis observed with hematoxylin and eosin(HE)staining and tartrate-resistant acid phosphatase(TRAP)staining;their serum alkaline phosphatase(ALP)and osteocalcin(BGP)activities detected by ELISA;their femoral mRNA expressions of Col-Ⅰ,OCN,and OPN detected by RT-qPCR;and their femoral protein expressions of OPG and RANKL detected by Western blot.Upon the MC3T3-E1 cells exposed to Dex and Shuangyi Capsules,their viability was evaluated by CCK-8 assay;their mineralization determined by alkaline phosphatase staining and alizarin red staining(ARS);and their intracellular ROS level detected using DCFH-DA probe.RESULTS Compared with the model group,Shuangyi Capsules groups demonstrated improved fracture of femoral trabeculae and reduced number of osteoclasts;increased serum ALP and BGP activities(P＜0.05,P＜0.01);increased femoral expressions of Col-Ⅰ mRNA and OPG protein(P＜0.05,P＜0.01);and decreased RANKL protein expression(P＜0.05).Compared with the MC3T3-E1 cells stimulated by Dex,those underwent further treatment of Shuangyi Capsules demonstrated increased cell viability and ALP activity(P＜0.05,P＜0.01);increased mineralization and calcium nodule formation;increased expressions of Col-Ⅰ,OCN,OPN mRNA and OPG protein(P＜0.05,P＜0.01);decreased RANKL protein expression(P＜0.05,P＜0.01);and reduced ROS levels.CONCLUSION Shuangyi Capsules ameliorate Dex-induced osteoporosis in mice by suppressing osteoclast overactivation,enhancing osteoblast activity,and stimulating bone formation through modulation of Col-Ⅰ,OCN,OPN mRNA and OPG/RANKL protein levels.

Objectives:We evaluated the clinical significance of unipolar electrogram and bipolar electrogram in guiding radiofrequency ablation for outflow tract ventricular premature contractions(PVC).Methods:Data were collected from 78 patients who underwent successful radiofrequency ablation of PVC.Pre-procedure electrocardiogram showed a LBBB morphology on inferior leads.In the included patients,the right-side ablation was performed at first,and if the ablation failed,the left-side ablation was then performed.According to the location of the successful ablation target,they were divided into unilateral ablation successful group and bilateral ablation successful group.The differences in the earliest bipolar local activation to QRS(LATBi),unipolar-dV/dTmax to QRS(LATUni),and local activation time were compared between the two groups.Furthermore,the electrogram characteristics predicting bilateral ablation were explored.Results:Patients were divided into unilateral ablation group(n=57)and bilateral ablation group(n=21)according to the ablation site.There were statistically significant differences in LATBi(25[21,30]ms vs.14[10,24]ms),LATUni(7[0,17]ms vs.-23[-41,-11]ms),and ΔLATBi-Uni(15[11,25]ms vs.44[25,56]ms)between the unilateral ablation group and the bilateral ablation group(all P<0.05).Multivariate regression analysis suggested that LATBi,LATUni,and ΔLATBi-Uni were independent predictors of the need for bilateral ablation.There was no significant difference between left and right LATBi,LATUni and ΔLATBi-Uni in the bilateral ablation group.LATUni≤-1 was the most accurate parameter for predicting the need for bilateral ablation(AUC=0.941;specificity 80.7%;sensitivity 100%).Conclusions:LATUni≤-1ms is a useful indicator for predicting the need for bilateral PVC ablation in this patient cohort.

Copper is one of the essential elements in the human body,playing various physiological roles.Maintai-ning copper homeostasis is crucial for health.Recent researches have uncovered that copper homeostasis imbalance is closely associated with the occurrence,progression,prognosis,and drug resistance of gynecological malignancies.The employment of copper and its complexes in antitumor therapy has emerged as a promising novel approach,attracting considerable research attention.Based on the relationship between copper homeostasis imbalance and gynecological tumors,this paper provides a concise review of the current status and progress of copper and its complexes in the treat-ment of gynecological tumors.

Objective To investigate the therapeutic effects of modified Lizhong Decoction on gastric and duodenal ulcers(GDU)of the spleen-stomach cold deficiency type,as well as its influence on gastric function and inflammatory mediators.Methods From April 2023 to May 2025,patients diagnosed with gastric dyspepsia of the spleen and stomach cold deficiency type at Nanyang First People's Hospital were randomly assigned to either the Western medicine group(n=53)or the combined therapy group(n=53).The Western medicine group received oral rabeprazole sodium enteric-coated tablets and sucralfate suspension,while the combined therapy group received the same Western medication regimen plus modified Lizhong Decoction.Both groups underwent a 6-week treatment course.Outcomes including clinical efficacy after 6 weeks,gastric mucosal morphology scores,gastric function,levels of inflammatory mediators,mucosal repair-related factors,oxidative stress markers,quality of life before and after treatment,and treatment safety were compared between the two groups.Results The total effective rate in the combined group after 6 weeks of treatment was significantly higher than that in the Western medicine group(P<0.05).After 6 weeks of treatment,both groups showed reduced mucosal thickness,inflammatory cell infiltration,glandular density scores,and decreased serum levels of cholecystokinin(CCK),motilin(MTL),gastrin(GAS),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),nuclear factor-κB(NF-κB),and malondialdehyde(MDA)compared to baseline,with greater reductions observed in the combined group(P<0.05).Additionally,serum levels of calcitonin gene-related peptide(CGRP),trefoil factor 1(TFF1),epidermal growth factor(EGF),epidermal growth factor receptor(EGFR),and superoxide dismutase(SOD),as well as quality-of-life scores across multiple domains,were significantly increased from baseline in both groups,with the combined group showing superior improvements(P<0.05).During the treatment period,the incidence of adverse reactions was 11.32%in the combined group and 5.66%in the Western medicine group,with no statistically significant difference between the two groups(P>0.05).Conclusion Modified Lizhong Decoction demonstrated a definite therapeutic effect on GDU of the spleen and stomach cold deficiency type,effectively improving gastric mucosal morphology,enhancing gastric function,suppressing inflammatory responses and oxidative stress,promoting the secretion of mucosal repair-related factors,improving patients'quality of life,and exhibiting favorable safety.

Objective To construct a diagnostic model for phlegm-dampness syndrome in hypertension based on multimodal feature fusion.Methods Clinical text information(physiological/lifestyle data,symptoms,pulse characteristics)and tongue image data were collected from 261 hypertension patients.For clinical text data,statistical analyses,including ANOVA,Mann-Whitney U test,and Chi-square test,were performed to identify significant features(P<0.05),which were incorporated into a clinical text-based diagnosis model(CTDM)using a multilayer perceptron algorithm.For tongue images,a tongue image-based diagnosis model(TIDM)was constructed based on channel attention mechanisms and residual networks.A multimodal diagnostic model(MDM)was built by fusing clinical text and tongue image features using a feature concatenation method.The diagnostic performance of each model was evaluated using five-fold cross-validation with the area under the receiver operating characteristic curve(AUC),accuracy,specificity,and sensitivity.Results Seven clinical text features,including physiological/lifestyle factors(disease duration,body mass index),symptoms(chest tightness,loss of appetite,excessive phlegm),and pulse characteristics(slippery pulse,damp pulse),were identified as risk factors for phlegm-dampness syndrome in hypertension.The AUC of the CTDM was 0.831±0.021,the AUC of the TIDM was 0.878±0.035,and the MDM achieved an AUC of 0.972±0.015.Conclusion The multimodal diagnostic model that integrates clinical text and tongue image features demonstrates high diagnostic accuracy and provides valuable guidance for AI-assisted diagnosis of phlegm-dampness syndrome in hypertension.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.