1.Syndrome Differentiation and Treatment Mechanisms of Inflammatory Injury in Diabetic Cardiomypathy from Theory of "Gaozhuo"
Xiaoyue WANG ; Yunfeng YU ; Xiangning HUANG ; Yixin XIANG ; Sihao ZHANG ; Qin XIANG ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):235-244
Diabetic cardiomyopathy (DCM) is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM, the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion, and divides the pathological process into three phases: Gaozhuo invasion, turbid heat damage to the channels, and turbid blood stasis and heat junction. Among them, the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors, and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress, it eventually develops into a depletion of the heart Yang, leading to the ultimate regression of heart failure. According to the theory of Gaozhuo, traditional Chinese medicine (TCM) should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause, and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat, strengthening the spleen and tonifying the kidney, and clearing heat and resolving turbidity should be the therapy. If the turbidity, stasis, and heat are knotted in the heart and collaterals, strengthening the spleen and tonifying the kidney, and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity, benefiting Qi and clearing heat to resolve turbidity, and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors, improve the inflammatory damage to myocardium and blood vessels, myocardial fibrosis, and cardiac systole and diastole, and thus slow down the onset and progression of DCM.
2.Effect of elbow-wrist functional orthosis on plantar pressure and balance function in stroke patients with hemiplegia
Cheng WU ; Yunfeng ZHANG ; Weining WANG ; Kewei YU ; Yanzheng ZHANG ; Jiarong SHEN ; Yi WU
Chinese Journal of Rehabilitation Theory and Practice 2026;32(1):30-39
ObjectiveTo explore the effect of elbow-wrist functional orthosis on plantar pressure distribution and balance function in stroke patients with hemiplegia. MethodsFrom June, 2024 to April, 2025, 60 patients with post-stroke hemiplegia were recruited from Huashan Hospital, Fudan University, and Shanghai Hebin Rehabilitation Hospital. They were randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine neurological rehabilitation, while the intervention group received additional training with an elbow-wrist functional orthosis on the affected side, for eight weeks. Before and after intervention, the Modified Ashworth Scale (MAS) of the elbow joint, plantar pressure symmetry index (SI), plantar contact area and mean plantar pressure were recorded, and balance and mobility were assessed using the Berg Balance Scale (BBS), Timed Up & Go Test (TUGT) and 10-Meter Walk Test (10MWT). ResultsTwo cases dropped out in the control group. After treatment, MAS grades of the elbow joint, forefoot SI, affected side plantar pressure area, BBS scores, TUGT and 10MWT of both groups improved (|Z| > 3.969, |t| > 3.528, P < 0.01), while the hindfoot SI and average pressure of the affected foot improved in the intervention group (∣t∣ > 4.264, P < 0.001). Except for TUGT and 10MWT, the intervention group was superior to the control group (∣Z∣ > 2.030, ∣t∣ > 2.096, P < 0.05). ConclusionThe elbow-wrist functional orthosis can enhance balance function in stroke patients with hemiplegia by reducing upper-limb spasticity, optimizing center-of-gravity distribution, and improving postural control.
3.Engineering of mesenchymal stem cell-derived exosomes and their application progress in the field of oral medicine
ZHAO Yunfeng ; LIU Qian ; LI Meng ; LI Luying ; ZHANG Wei ; HU Xiantong ; MA Chufan
Journal of Prevention and Treatment for Stomatological Diseases 2025;33(9):792-800
In recent years, mesenchymal stem cell-derived exosomes (MSC-EXO) have garnered increasing attention in the field of stomatology and have become an established research area in biomedical research. This article reviews the engineering of exosomes derived from mesenchymal stem cells and their application in the field of stomatology, in order to provide new ideas for the development of stomatology. Exosomes are nanoscale membrane vesicles secreted by cells and contain a variety of proteins, RNAs, lipids, and other biomolecules. They are transported through the circulatory system and can interact with other cells to regulate their biological behavior and participate in a variety of physiological and pathological processes. In the treatment of oral diseases, exosomes have shown great potential due to their natural biological activity and versatility. However, studies have found that relying solely on the function of natural exosomes may not fully meet the complex clinical requirements. Therefore, the concept of engineered exosomes has emerged. Engineered exosomes can be modified by bioengineering technology to enhance their targeting, allowing them to reach the lesion site more accurately. At the same time, engineered exosomes can also be surface modified or loaded internally to carry specific therapeutic molecules, such as drugs, gene editing tools or signaling molecules to improve the therapeutic effect. In addition, this engineered treatment can also confer greater stability to exosomes, making them better able to resist clearance by the immune system when circulating in the body, extending their half-life, and improving the effectiveness of treatment. Although engineered exosomes have attracted extensive attention in the fields of stomatology and other fields, their application is still mainly in the stage of basic research. To promote the clinical application of engineered exosomes, it is necessary to provide more sufficient evidence of biocompatibility and clarify their therapeutic effect and mechanism.
4.Progress and Evaluation of Animal Model of Heart Qi-Yin Deficiency Syndrome
Yayi LIU ; Yunfeng JIA ; Yiming ZUO ; Junping ZHANG ; Shichao LÜ
Laboratory Animal and Comparative Medicine 2025;45(4):411-421
Animal models combining disease and syndrome are important research tools to explore the nature of traditional Chinese medicine (TCM) syndromes. At present, the construction and evaluation methods of animal models have preliminarily established the foundation for standardized development. Qi-yin deficiency syndrome is a common type of TCM syndrome in cardiovascular diseases. It is an important pathogenic factor causing the onset, pathological damage, and chronic nature of cardiovascular diseases, as well as triggering other illnesses. The establishment of an animal model of cardiovascular disease with the characteristics of Qi-yin deficiency, along with an objective and standardized evaluation system, has become an important part of modern cardiovascular disease research. In recent years, research on the construction and evaluation of animal models of heart Qi-yin deficiency syndrome has increased, but the construction methods and evaluation criteria vary. Compared with other animal models, the literature is limited, lacking statistics and overall analysis. Therefore, based on the scientific connotation of heart Qi-yin deficiency syndrome, this article systematically reviews the evaluation system of its animal model, covering multidimensional methods such as macroscopic characterization assessment, physicochemical indicators and objective evaluation, and syndrome differentiation based on prescriptions. The specific model construction strategies are described, including single-factor induction methods (sleep deprivation, chronic intermittent hypoxia, arterial occlusion, high-salt feeding) and the compound-factor induction methods (sleep deprivation combined with drug method, chronic intermittent hypoxia combined with drug method, exhaustive swimming combined with drug method). Meanwhile, application examples of each model in the research are listed, the existing problems in the current model construction and evaluation are analyzed, and optimization directions are proposed, such as promoting the compound factor induction strategy and improving the objectivity of the evaluation criteria. This article aims to provide theoretical references for constructing an animal model of heart Qi-yin deficiency syndrome that conforms to TCM characteristics, and thereby laying a scientific foundation for the prevention and treatment of cardiovascular diseases with TCM.
5.Current status and reflections on research of intelligent acupuncture-moxibustion medical equipment.
Ling CHENG ; Muqiu TIAN ; Yanling PING ; Shuqing LIU ; Yunfeng WANG ; Jun ZHANG ; Qiaofeng WU
Chinese Acupuncture & Moxibustion 2025;45(10):1396-1404
Intelligent acupuncture-moxibustion medical equipment is an important force in promoting the inheritance, innovation, and modernization of acupuncture-moxibustion. This paper reviews the development status of intelligent acupuncture-moxibustion medical equipment and related new technologies, as well as the challenges faced. It is found that, with the advancement of technologies such as big data and artificial intelligence, acupuncture-moxibustion medical equipment has shown characteristics of greater precision, miniaturization, intelligence, and portability. However, deficiencies remain in areas such as standardization and regulation, including relatively low rates of effective transformation and a lack of innovation in research outcomes. Therefore, there is an urgent need to formulate corresponding strategies: improving the development of relevant standards for intelligent acupuncture-moxibustion medical equipment, encouraging the integration of medicine and engineering, cultivating interdisciplinary talents, and strengthening the protection of invention patents. It is necessary to establish a demand-oriented pathway connecting "equipment development, equipment evaluation, product formation" through multiple stages such as talent training and research project initiation, thereby promoting the modernization and standardization of intelligent acupuncture-moxibustion medical equipment and supporting the revitalization of traditional medicine.
Moxibustion/instrumentation*
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Humans
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Acupuncture Therapy/trends*
;
Artificial Intelligence
6.Defect modification of calcium silicate and its application in oral bacteriostasis and tooth remineralization.
Yuanyuan HU ; Shuyan ZHANG ; Jianhua ZHANG ; Hongrong LUO ; Yunfeng LI ; Jing ZHANG ; Xianchun CHEN
West China Journal of Stomatology 2025;43(5):648-659
OBJECTIVES:
Calcium silicate (CSO) is modified to give it photothermal antibacterial properties. Its application potential in tooth mineralization and oral antibacterial is evaluated.
METHODS:
Based on defect-engineering modification strategy, a series of CSO-T samples (CSO-300, CSO-400, CSO-500, CSO-600) was obtained by introducing oxygen vacancy into CSO through thermal reduction using sodium borohydride. The samples were tested using scanning electron microscopy (SEM), X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet near-infrared absorption spectroscopy, and infrared thermography. The powder samples with the best photothermal performance and the most suitable material concentration (CSO-500, 500 μg/mL) were selected for subsequent experiments. High resolution transmission electron microscopy was used to analyze the microstructure and morphology of the sample, and MTT assay and Calcein AM/PI live/dead cell staining were used to evaluate the toxicity and compatibility of the sample to human oral keratinocytes. Escherichia coli and Staphylococcus aureus were selected for photothermal antibacterial experiments to evaluate their in vitro antibacterial performance. SEM, energy dispersive spectrometer, and micro Vickers hardness tester were used to evaluate the ability of materials to induce in vitro remineralization of detached teeth.
RESULTS:
Oxygen vacancies changed the crystal type and lattice spacing of CaSiO3, broadened the light-absorption range, and gave it a good photothermal conversion ability in response to near infrared. Invitro experiments showed that the modified CaSiO3 could promote the formation of hydroxyapatite on the tooth surface, thereby promoting the remineralization of teeth and improving the teeth hardness. Moreover, it had photothermal antibacterial properties and no cytotoxicity.
CONCLUSIONS
Defect-modified black calcium silicate has multiple functions, such as promoting tooth remineralization and photothermal bacteriostatic. When combined with the infrared luminescent toothbrush, it can simply and effectively treat tooth enamel erosion and oral bacteriostatic diseases caused by the excessive consumption of carbonated beverages and other daily bad living habits. This combination is expected to achieve the synergic treatment effect of tooth remineralization and oral bacteriostatic through daily cleaning is expected.
Calcium Compounds/pharmacology*
;
Silicates/pharmacology*
;
Humans
;
Staphylococcus aureus/drug effects*
;
Tooth Remineralization
;
Escherichia coli/drug effects*
;
Anti-Bacterial Agents/pharmacology*
;
Keratinocytes/drug effects*
;
Microscopy, Electron, Scanning
7.The mechanism of the effects of bisphenol A and high-fat diet on non-alcoholic fatty liver disease in mice
Yunfeng LIN ; Jiaoxiang ZHANG ; Zhilin ZHANG ; Zeqi LU ; Ruijuan YAO ; Lanlan XU ; Congzheng QI ; Lili LIU ; Qiansheng HU ; Wei ZHU
China Occupational Medicine 2025;52(4):376-385
Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.
8.Efficacy and safety of CA280 cytokine adsorption column in treatment of acute-on-chronic liver failure
Yan HE ; Dakai GAN ; Xiaoqing ZHANG ; Tao LONG ; Xuezhen ZHANG ; Wei ZHANG ; Yizhen XU ; Yuyu ZENG ; Rui ZHOU ; Shuanglan LIU ; Xizi JIANG ; Yushi LU ; Molong XIONG ; Yunfeng XIONG
Journal of Clinical Hepatology 2025;41(10):2093-2101
ObjectiveTo investigate the application of the novel inflammatory factor adsorption column CA280 combined with low-dose plasma exchange (LPE) in patients with acute-on-chronic liver failure (ACLF). MethodsA prospective cohort study was designed, and a total of 93 ACLF patients who were admitted to The Ninth Hospital of Nanchang from June 2023 to January 2025 were enrolled and randomly divided into DPMAS+LPE group with 50 patients and CA280+LPE group with 43 patients. In addition to comprehensive medical treatment, the patients in the DPMAS+LPE group received DPMAS and LPE treatment, and those in the CA280+LPE group received CA280 and LPE treatment. The two groups were observed in terms of routine blood test results, liver function parameters, renal function markers, electrolytes, coagulation function parameters, cytokines, adverse events, and 28-day prognosis before surgery (baseline), during surgery (DPMAS or CA280), and after surgery (after sequential LPE treatment). The paired t-test was used for comparison of normally distributed continuous data before and after treatment within each group, and the independent-samples t test was used for comparison between groups; the Wilcoxon signed-rank test was used for comparison of non-normally distributed continuous data before and after treatment within each group, and the Mann-Whitney U test was used for comparison between groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups, and the Spearman test was used for correlation analysis. ResultsAfter CA280 treatment, the ACLF patients had significant reductions in the levels of cytokines (IL-6, IL-8, IL-10, TNF-α, and IFN-γ), liver function parameters (ALT, AST, ALP, TBil, DBil, Alb, and glutathione reductase), and the renal function marker urea nitrogen (all P<0.05), and in terms of coagulation function parameters, there were significant increases in prothrombin time, activated partial thromboplastin time (APTT), thrombin time, and international normalized ratio (INR) and significant reductions in prothrombin activity (PTA) and fibrinogen (FIB) (all P<0.05). Compared with the DPMAS+LPE group, the CA280+LPE group showed better improvements in the serum cytokines IL-8 (Z=-2.63, P=0.009), IL-10 (Z=-3.94, P<0.001), and TNF-α (Z=-1.53, P=0.023), and the two artificial liver support systems had a similar effect in improving liver function (ALT, AST, GGT, GR, TBil, and DBil) (all P >0.05), but the CA280+LPE group showed a significantly greater reduction in Alb (Z=-2.08, P=0.037). CA280+LPE was more effective in reducing uric acid (Z=-2.97, P=0.003). Compared with DPMAS+LPE, CA280+LPE treatment resulted in a significant reduction in INR (Z=-4.01, P<0.001), a significant increase in APTT (Z=-2.53, P=0.011), and significant greater increases in PTA (Z=-6.28, P<0.001) and FIB (Z=-3.93, P<0.001). There were no significant differences in the incidence rates of adverse reactions and the rate of improvement at discharge between the two groups (all P>0.05). The Spearman correlation analysis showed that IL-6 was significantly correlated with WBC (r=0.22, P=0.042), TBil (r=0.29, P=0.005), and FIB (r=-0.33, P=0.003); IL-8 was positively correlated with APTT (r=0.37, P<0.001) and INR (r=0.25, P=0.013); TNF-α was significantly correlated with WBC (r=0.40, P<0.001) and TBil (r=0.34, P<0.001). ConclusionCompared with DPMAS, CA280 combined with LPE can effectively clear proinflammatory cytokines and improve liver function in ACLF patients, but it has a certain impact on Alb and coagulation function. This regimen provides a new option for the individualized treatment of ACLF and can improve the short-term prognosis of patients, but further studies are needed to verify its long-term efficacy.
9.Expression and biological role of C1GALT1 in glioblastoma
Xin Ao ; Yunfeng Long ; Zhengrong Zhang ; Mingzhu Zhang ; Zhuang Le ; Yanting Su
Acta Universitatis Medicinalis Anhui 2025;60(6):992-999
Objective :
To explore the expression profile of core 1 β1,3-galactosyltransferase 1(C1GALT1) in glioblastoma(GBM) and to elucidate its impact on the initiation and progression of GBM.
Methods :
The expression levels and prognostic significance of C1GALT1 in GBM were analyzed using the GEPIA and CGGA databases. Two representative glioblastoma cells(U251 and LN18) were selected to construct C1GALT1-knockdown cell lines and performed in vitro experiments. The Cell Counting Kit-8(CCK-8) and Transwell assays were employed to evaluate the impact of C1GALT1 on proliferation, migration and invasion of GBM cells. Transcriptome data were analyzed to identify potential signaling pathways. Senescence β-Galactosidase Staining Kit was used to detect β-galactosidase activity.
Results :
nalysis of GEPIA and CGGA databases revealed that C1GALT1 was significantly upregulated in GBM tissues compared to adjacent non-cancerous tissues (P < 0. 05) , and its high expression was associated with poor prognosis of patients (P < 0. 000 1) . The CCK-8 experiment demonstrated a significant reduction in prolifera- tion rate following C1GALT1 knockdown (P < 0. 05) . Transwell assay showed that cell migration and invasion de- creased after C1GALT1 was knocked down ( P < 0. 001) . Transcriptome sequencing and senescence β-galactosi- dase staining showed that C1GALT1 was involved in the cellular senescence signaling pathway , and the activity of β-galactosidase associated with cellular senescence significantly increased after C1GALT1 was knocked down(P < 0. 05) .
Conclusion
C1GALT1 is overexpressed in GBM tissues and may promote the proliferation , migration and invasion of GBM cells by inhibiting cellular senescence .
10.Study on the ADC value of deep gray matter nuclei in patients with Parkinson's disease by RESOLVE DWI
Lishu ZHU ; Xinyou LI ; Bin YU ; Yunfeng LU ; Zhiwei ZHANG ; Yongmei LI ; Fajin LYU ; Silin DU
Chongqing Medicine 2025;54(4):915-920
Objective Readout segmentation of long variable echo-trains diffusion weighted imaging(RESOLVE DWI)was used to analyze the difference of apparent diffusion coefficient(ADC)value in deep cerebral nucleus and its correlation with clinical characteristics in patients with Parkinson's disease(PD).Methods Clinical data of 60 patients with PD were retrospectively analyzed as PD group,and were divided in-to the tremor group(n=30)and the bradykinesia group(n=30)according to symptom type,middle-aged(≤65 years old)group(n=23)and elderly(>65 years old)group(n=37)according to age,and 60 healthy vol-unteers were selected as the control group during the same period.ADC values were measured on the ADC map of RESOLVE DWI sequence,and the ADC values of bilateral putamen,pallidus,substantia nigra,rubra,and dentate nucleus were analyzed and their correlation with UPDRS-Ⅲ score and H&Y grading.Results Compared with the control group,the ADC values of both putamen,globus pallidus,globus pallidus,red nucleus,right substantia nigra and right dentate nucleus were increased in the PD group,the ADC values of both putamen,globus pallidus,red nucleus and right substantia nigra in the tremor group were increased,and the ADC values of right putamen,globus pallidus and bilateral red nucleus in the bradykinesia group were increased(P<0.05).Compared with the bradykinesia group,the values of ADC in the tremor group were similar.Compared with the middle-aged group,the ADC values of right putamen,bilateral globus pallidus,left substantia nigra and left red nucleus were higher in the elderly group(P<0.05).In the PD group,the ADC values of the right putamen,globus pallidus,and dentate nucleus were positively correlated with H&Y grade and UPDRS-Ⅲscore,and the ADC value of the left putamen was positively correlated with H&Y grade.Conclusion RE-SOLVE DWI can be used to evaluate the differences in deep gray matter nuclei in PD patients,and its ADC value may be used to evaluate and predict the severity of nuclear mass damage and motor symptoms in PD pa-tients.


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