1.Morphologic and functional effect of core training combined with respiratory training on multifidus and transversus abdominis in patients with lumbar disc herniation
Jianing SONG ; Xiaole LOU ; Huan LIU ; Xue HAN ; Lei XU ; Min WANG
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):107-116
ObjectiveTo explore the effect of respiratory training based on core stabilization training on lumbar disc herniation. MethodsFrom January, 2023 to October, 2024, 96 patients with lumbar disc herniation admitted to the First Affiliated Hospital of Bengbu Medical University were divided into control group (n = 32), core group (n = 32) and respiratory group (n = 32). All the groups underwent conventional rehabilitation therapy, with core stabilization training in the core group and respiratory training combined with core stabilization training in the respiratory group, additionally, for four weeks. Before and after training, the scores of Visual Analogue Scale, Japanese Orthopaedic Association (JOA) and Oswestry Dysfunction Index (ODI) were compared, the average electromyographic value (AEMG) and root mean square (RMS) value of the multifidus and transversus abdominis were detected by surface electromyography (sEMG); and the thickness of the multifidus and transversus abdominis were measured by musculoskeletal ultrasonography bilaterally. ResultsThe intra-group effect (F > 597.796, P < 0.001), inter-group effect (F > 16.535, P < 0.001) and interaction effect (F > 49.622, P < 0.001) were significant in the scores of VAS, JOA and ODI; which were better in the respiratory group than in the control group and the core group (P < 0.05), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 7971.631, P < 0.001), inter-group effect (F > 177.760, P < 0.001) and interaction effect (F > 478.771, P < 0.001) were significant in the thickness of the transversus abdominis and multifidus; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 144303.007, P < 0.001), inter-group effect (F > 1495.458, P < 0.001) and interaction effect (F > 3121.361, P < 0.001) were significant in the RMS of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and the core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). The intra-group effect (F > 1890.532, P < 0.001), inter-group effect (F > 607.132, P < 0.001) and interaction effect (F > 824.923, P < 0.001) were significant in the AEMG of the multifidus and transversus abdominis; which were better in the respiratory group than in the control group and core group (P < 0.001), and were better in the core group than in the control group (P < 0.001). ConclusionCore training combined with respiratory training can more effectively reduce pain and improve dysfunction by enhancing the strength and control of the core muscles, thus improving the quality of life of patients with lumbar disc herniation.
2.Mechanism of Cangxitongbi Capsules in Mediating Chondrocyte Pyroptosis in Knee Osteoarthritis via Regulating p38 MAPK/NLRP3/Caspase-1 Pathway
Zhimeng ZHANG ; Daotong YUAN ; Ximin JIN ; Rui GONG ; Zhenlong SONG ; Yongkui ZHANG ; Xiaole WANG ; Rongxiu BI ; Wenpeng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):61-68
ObjectiveTo explore the mechanism of Cangxi Tongbi capsules (CXTB) in regulating the p38 mitogen-activated protein kinase (p38 MAPK)/NOD-like receptor protein 3 (NLRP3)/cysteine protease-1 (Caspase-1) signaling pathway to inhibit pyroptosis of cartilage cells in knee osteoarthritis (KOA). MethodSixty male SD rats were randomly divided into a sham operation group, a model group, low, medium, and high dose CXTB groups, and a positive control group, with 10 rats per group. The modified Hulth method was employed to establish a rat model of KOA. According to their respective assignments, rats were administered CXTB (0.25, 0.5, 1.0 g·kg-1) and Celecoxib (24 mg·kg-1) by gavage. The sham operation and model groups were given an equivalent volume of physiological saline. Treatment was performed once daily for 28 days. Micro-computed tomography (Micro-CT) was used to assess bone volume/total volume (BV/TV) and trabecular separation (Tb.Sp). Joint degeneration was evaluated through hematoxylin-eosin (HE) staining, safranin-fast green (SO) staining, and Osteoarthritis Research Society International (OARSI) scoring. Western blot analysis was conducted to measure the expression levels of p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK), NLRP3, Caspase-1, and gasdermin D (GSDMD) proteins. Real-time PCR was used to assess mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD genes. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-18 (IL-18). After knee replacement surgery, cartilage tissue was analyzed using Western blot to assess the protein expression levels of p38 MAPK, p-p38 MAPK, NLRP3, Caspase-1, and GSDMD, and Real-time PCR was used to evaluate gene expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD. ResultMicro-CT analysis revealed significant narrowing of the joint space and increased bone spur formation in KOA rats compared with the sham operation group, with a decrease in BV/TV ratio and an increase in Tb.Sp value (P<0.01). Serum levels of TNF-α, IL-1β, and IL-18 were elevated (P<0.01). The protein expression levels of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD in cartilage were significantly increased (P<0.01), and the mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD were also enhanced (P<0.01). Significant differences in protein expression of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD were observed between normal and diseased cartilage tissues after knee replacement surgery (P<0.05), and the gene expression of p38 MAPK, NLRP3, Caspase-1, and GSDMD were also significantly different (P<0.01). HE and SO staining showed roughened joint surfaces, reduced cartilage thickness, and disordered cellular arrangement in KOA rats. OARSI scores were significantly higher (P<0.01). Compared with the model group, treatment with low, medium, and high concentrations of CXTB resulted in increased BV/TV ratios and decreased Tb.Sp values in the knee joints of rats (P<0.01). HE and SO staining indicated a trend towards smoother joint surfaces and reduced OARSI scores (P<0.01). The protein expression levels of p-p38 MAPK, NLRP3, Caspase-1, and GSDMD were notably decreased (P<0.05), as were the mRNA expression levels of p38 MAPK, NLRP3, Caspase-1, and GSDMD (P<0.01). Additionally, serum concentrations of TNF-α, IL-1β, and IL-18 were significantly reduced (P<0.01). ConclusionCXTB intervention may alleviate knee joint degeneration in KOA rats and inhibit the expression of inflammatory factors and pyroptosis of cartilage cells, thereby protecting cartilage. The underlying mechanism may involve modulation of the p38 MAPK/NLRP3/Caspase-1 signaling pathway.
3.Prediction of Triple-Negative Breast Cancer Based on Digital Mammography Radiomics Nomogram:A Multicenter Study
Yuhai XIE ; Peiqi MA ; Jianjian HAN ; Xiaole WANG ; Dong HU ; Wenjun MA ; Tianxian WEI ; Yang YANG
Chinese Journal of Medical Imaging 2024;32(11):1140-1146
Purpose To investigate the clinical value of multi-center digital mammography radiomics nomogram model in predicting triple-negative breast cancer(TNBC).Materials and Methods The digital mammograms of 462 patients with pathologically confirmed breast cancer from November 2016 to March 2022 were retrospectively analyzed,including 243 cases from Yijishan Hospital of Wannan Medical College(institution 1),106 cases from Fuyang People's Hospital(institution 2)and 113 cases from Taihe People's Hospital(institution 3).According to the results of immunohistochemistry,a total of 349 breast cancer patients in institution 1 and institution 2 were randomly divided into the training group(244 cases,including 41 TNBC and 203 non-TNBC)and the validation group(105 cases,including 18 TNBC and 87 non-TNBC)according to the ratio of 7∶3,113 breast cancer patients(24 TNBC and 89 non-TNBC)from institution 3 were included in the external validation group.Comparing the mediolateral oblique and cranial cauda digital mammography images,the mammography imaging with larger lesion areas were selected,and the image segmentation and radiomics feature extraction were performed.The radiomics model was constructed by using Logistic regression.The clinicopathological parameters and radiomics scores were used to construct a nomogram.Receiver operating characteristic and decision curve analysis were used to evaluate the model performance.To compare The predictive performance between the models was compared.Results Finally,four radiomics features closely related to TNBC were selected to construct an radiomics model.The area under the curve,sensitivity and specificity of TNBC predicted by the radiomics model in training group,validation group and external test group were 0.868,90.24%and 72.91%,0.827,72.22%and 75.86%,0.837,70.83%and 78.65%,respectively.The area under the curve,sensitivity and specificity of TNBC predicted by the combined model in the training group,validation group and external test group were 0.903,80.49%and 86.70%,0.890,77.78%and 88.51%,0.870,62.50%and 85.39%,respectively.The combined model was better than the single image omics model in predicting TNBC,and the difference was statistically significant between the training group and the verification group(Z=2.061,2.064,both P<0.05),but not between the external test group(Z=1.223,P=0.221).In three group,decision curve analysis showed that the nomogram predicted a higher net benefit than the radiomics model for triple-negative breast cancer.Conclusion The radiomics model has high diagnostic efficiency in predicting TNBC,and the nomogram model combined with the radiomics score and histological grading can further improve the prediction efficiency.
4.MicroRNA-145-5p Regulates the Epithelial-Mesenchymal Transition in Nasal Polyps by Targeting Smad3
Mengyu ZHANG ; Xiaole PENG ; Xiaolong LIANG ; Wentao WANG ; Yuqing YANG ; Fan XU ; Xiaomin LU ; Dechun GENG ; Manyi LI
Clinical and Experimental Otorhinolaryngology 2024;17(2):122-136
Objectives:
. The annual prevalence of chronic rhinosinusitis (CRS) is increasing, and the lack of effective treatments imposes a substantial burden on both patients and society. The formation of nasal polyps in patients with CRS is closely related to tissue remodeling, which is largely driven by the epithelial-mesenchymal transition (EMT). MicroRNA (miRNA) plays a pivotal role in the pathogenesis of numerous diseases through the miRNA-mRNA regulatory network; however, the specific mechanism of the miRNAs involved in the formation of nasal polyps remains unclear.
Methods:
. The expression of EMT markers and Smad3 were detected using western blots, quantitative real-time polymerase chain reaction, and immunohistochemical and immunofluorescence staining. Differentially expressed genes in nasal polyps and normal tissues were screened through the Gene Expression Omnibus database. To predict the target genes of miR-145-5p, three different miRNA target prediction databases were used. The migratory ability of cells was evaluated using cell migration assay and wound healing assays.
Results:
. miR-145-5p was associated with the EMT process and was significantly downregulated in nasal polyp tissues. In vitro experiments revealed that the downregulation of miR-145-5p promoted EMT. Conversely, increasing miR-145-5p levels reversed the EMT induced by transforming growth factor-β1. Bioinformatics analysis suggested that miR-145-5p targets Smad3. Subsequent experiments confirmed that miR-145-5p inhibits Smad3 expression.
Conclusion
. Overall, miR-145-5p is a promising target to inhibit nasal polyp formation, and the findings of this study provide a theoretical basis for nanoparticle-mediated miR-145-5p delivery for the treatment of nasal polyps.
5.Mashao Pingchuan Decoction Inhibites Autophagy in Airway Epithelial Cells Through PI3K/Akt/mTOR Signaling Pathway
Yanqun REN ; Xiaole WANG ; Tong LIU ; Lu ZHANG ; Xinheng WANG ; Di WU ; Huanzhang DING ; Zegeng LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(3):88-95
ObjectiveTo investigate the effect of Mashao Pingchuan decoction (MSPC) on lipopolysaccharides (LPS)-induced autophagy in human bronchial airway epithelial cells (16HBE) via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Method16HBE cells were selected for the study, and cell counting kit-8 (CCK-8) was used to detect the activity of of LPS-induced 16HBE cells and the effect of MSPC-containing serum on the cells. Suitable LPS-induced 16HBE cells were screened by the CCK-8 method, and the content of tumor necrosis factor-α (TNF-α) was measured to identify the established model. And MSPC-containing serum was prepared. The cells were divided into normal group, LPS group, LPS+MSPC group, LY294002+LPS group and LY294002+LPS+MSPC group. Transmission electron microscopy was performed to observe the changes in autophagic vesicles and ultrastructure of the cells. Western blot was performed to detect the protein expressions of PI3K, phosphorylated PI3K (p-PI3K), Akt, phosphorylated Akt (p-Akt), mTOR, phosphorylated mTOR (p-mTOR) and microtubule-associated protein 1 light chain 3B (LC3B), and enzyme-linked immunosorbent assay (ELISA) was used to detect the expressions of inflammatory factors interleukin-5 (IL-5), IL-6, TNF-α and IL-10 in the five groups. ResultLPS inhibited the 16HBE cells in a dose-dependent manner. Compared with the normal group, the LPS group (150 mg·L-1 of LPS) increased the expression of pro-inflammatory factor TNF-α after 24 h of treatment (P<0.05) and facilitated the autophagosome formation, and MSPC-containing serum exerted a concentration-dependent promotion effect on the 16HBE cells, inhibited the autophagy to a certain degree and enhanced the cell status. Western blot revealed that the protein expressions of p-PI3K, p-Akt and p-mTOR in the model group were lower (P<0.05) and the protein expression of LC3B was higher (P<0.01) than those in the normal group. Compared with the conditions in the LPS group, the protein expressions of p-PI3K, p-Akt and p-mTOR in the LPS+MSPC group were elevated (P<0.05) and that of LC3B was reduced (P<0.05). Compared with the LPS+LY294002 group, the LY294002+LPS+MSCP group had up-regulated protein expressions of p-PI3K, p-Akt and p-mTOR (P<0.05) and down-regulated protein expression of LC3B (P<0.05). ELISA showed that the LPS group had higher levels of IL-5, IL-6, TNF-α and IL-10 than the normal group, while the levels of TNF-α, IL-6 and IL-8 were decreased (P<0.01) and the level of IL-10 was increased (P<0.01) after treatment with MSCP. ConclusionMSCP may lower the LPS-induced autophagy in 16HBE cells and improve the inflammatory response through activating the PI3K/Akt/mTOR signaling pathway.
6.Construction and application effect of teaching resources of human physiology course from the perspective of demand analysis theory
Yunping ZHANG ; Pei CHEN ; Shizhen WANG ; Xiaole ZHANG ; Bingzhong XU
Chinese Journal of Medical Education Research 2023;22(1):57-61
Objective:Based on the theory of demand analysis theory, to build teaching resources of human physiology course and explore its application effect.Methods:The three-year nursing junior college students of Batch 2018 were selected as the research objects. According to the principle of randomization, the students were divided into the observation group (97 cases) and control group (99 cases). Students in the observation group used integrated teaching resources from the perspective of demand analysis, while students in the control group used traditional curriculum resources. After the end of the course, the differences between the two groups of students' theoretical and practical assessment results and teaching experience were compared SPSS 20.0 was used for t test. Results:The results of theoretical [(73.67±8.76) vs. (70.48±8.36)] and practical skills [(84.41±4.83) vs. (83.63±4.27)] in the observation group were significantly different from those in the control group ( P<0.05). The overall scores of 9 teaching effect sub-items, such as learning awareness of inquiry, independent learning ability and critical thinking ability, were significantly higher than those of the control group ( P<0.01). Conclusion:The construction of human physiology teaching resources based on demand analysis theory can improve the effectiveness and pertinence of resource construction, and the effective use of resources in teaching can significantly improve the teaching effect, stimulate students' subjective initiative, cultivate their comprehensive ability and improve classroom efficiency.
7.Clinical evaluation of two different peritoneal dialysis catheter removal methods in elderly patients on peritoneal dialysis
Shengxue ZHANG ; Xiaole SU ; Yan YAN ; Yan ZHAO ; Xinyan LIU ; Xiaoxia LI ; Yan ZHANG ; Lihua WANG
Chinese Journal of Geriatrics 2022;41(2):191-195
Objective:To assess two methods for peritoneal dialysis catheter removal in elderly patients on peritoneal dialysis.Methods:A retrospective cohort study was conducted and clinical data were collected for 107 elderly patients on peritoneal dialysis with catheters removed at the peritoneal dialysis center of the Second Hospital of Shanxi Medical University from August 2010 to May 2020.The 107 patients were divided into the open surgical extubation group and the 'pull' technique group.Sex, age, disease leading to dialysis, dialysis age, reason for extubation and preoperative test results were compared between the two groups.Operative time, length of postoperative hospitalization, perioperative pain and postoperative complications of the two groups were examined.Results:Higher levels or values were observed in operative time[(71.2±13.4)min vs.(19.3±5.6)min, t=16.933, P<0.01], length of postoperative hospitalization[(9.5±1.8)d vs.(2.2±0.5)d, t=10.988, P<0.01]and intraoperative pain score(4.4±1.6 vs.1.4±1.1, t=6.909, P<0.01)and pain score 24h after surgery(3.7±1.4 vs.0.5±0.3, t=9.995, P<0.01)in the open surgical extubation group than in the 'pull' technique group, but there was no statistical difference in the incidence of postoperative complications between the two groups(6.8% vs.5.0%, χ2=0.037, P>0.05). Conclusions:either the open surgical removal method or 'pull' technique.can safely and effectively remove the peritoneal dialysis catheter in elderly patients on peritoneal dialysis of the two methods, the 'pull' technique has advantages including less trauma, shorter and simpler surgery, helping achieve improved quality of life for elderly patients on peritoneal dialysis.
8.Analysis of clinical prognosis of endoscopic salvage surgery in patients with rT2 recurrent nasopharyngeal carcinoma
Xiaole SONG ; Wanpeng LI ; Jingyi YANG ; Huankang ZHANG ; Huan WANG ; Kai XUE ; Quan LIU ; Xicai SUN ; Hongmeng YU ; Dehui WANG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2022;57(12):1442-1449
Objective:To investigate the feasibility of endoscopic salvage surgery for patients with rT2 recurrent nasopharyngeal carcinoma (rNPC) and to analyze their prognostic factors.Methods:The clinical data of 33 patients with rT2 rNPC who underwent endoscopic extended nasopharyngectomy in Eye & ENT Hospital Affiliated to Fudan University from January 2015 to July 2020 were analyzed, including 29 males (87.9%) and 4 females (12.1%), aging (51.7±10.6) years. The clinicopathological characteristics of these patients were recorded and analyzed, in terms of gender, sex, alcohol and cigarette use, interval between primary treatment to recurrence, adjuvant therapy, lymph node metastasis, internal carotid artery (ICA) invasion, necrosis, margin and reconstruction materials. Kaplan Meier analysis was used to plot the overall survival rate and progression free survival rate curve, Log-rank test was used to analyze the prognostic factors among patients, and multivariate Cox proportional hazards regression was used to determine the independent risk factors of tumor progression free survival.Results:Among 33 patients with rT2 rNPC, the recurrence interval of 24 patients with rNPC after primary radiotherapy was more than 2 years. A total of 25 patients received primary radiotherapy and adjuvant chemotherapy at the same time. There were 6 cases with cervical lymph node metastasis, 12 cases with ICA invasion, 8 cases with positive surgical margin, 7 cases underwent ICA embolization before operation. A total of 18 cases underwent pedicled tissue flap repairment after operation, including 12 pedicled nasal septal mucosa flaps and 6 temporalis muscle flaps. The median follow-up time was 15 months. Five patients died because of disease progression (in 2 cases), post surgical ICA hemorrhage (in 1 case), liver metastasis (in 1 case) and dysphagia (in 1 case). The 1-year, 2-year and 3-year overall survival rates of all patients were 93.9%, 81.8% and 81.8%, respectively. The 1-year, 2-year and 3-year progression free survival rates were 74.7%, 59.7% and 40.9%, respectively. Log-rank statistical analysis showed that the positive surgical margin ( P=0.060) and recurrence interval ( P=0.151) were possibly related to the prognosis of rT2 rNPC. Multivariate Cox regression analysis showed that the positive surgical margin was an independent risk factor for patients with rT2 rNPC ( P=0.034). Nasopharynx hemorrhage occurred in 4 patients, skull base bone necrosis occurred in 2 patients, trismus occurred in 3 patients, and no obvious brain complications occurred in 7 patients with ICA embolization. Conclusion:Endoscopic salvage surgery for rT2 rNPC is a safe and effective surgical option, but the long-term effect still needs long-term follow-up in bulk cases.
9.Analysis of GCH1 gene variant in a consanguineous Chinese pedigree affected with tetrahydrobiopterin deficiency
Xiaole LI ; Dengna ZHU ; Su′na LIU ; Chenlu JIA ; Yaqing GUO ; Linlin ZHANG ; Mingmei WANG ; Dehua ZHAO
Chinese Journal of Medical Genetics 2022;39(7):713-717
Objective:To explore the genetic basis for a child featuring tetrahydrobiopterin deficiency and global developmental delay.Methods:Clinical and laboratory examinations were carried out for the child. Genomic DNA of the patient was subjected to high-throughput sequencing to identify genetic variants associated with hyperphenylalaninemia. Candidate variants were verified by Sanger sequencing.Results:The result of blood tandem mass spectrometry showed that the Phenylalanine in the blood was 642.7 μmol/l, and the ratio of Phenylalanine/Tyrosine was 5.42. Analysis of urinary pterin: neopterin 0.09 mmol/mol Cr, biopterin 0.04 mmol/mol Cr, biopterin% 77%, which suggested tetrahydrobiopterin deficiency. The parents of the proband were first cousins. DNA sequencing revealed that the proband has harbored homozygous c. 353A>T variants in exon 2 of the GCH1 gene, for which his great grandmother, grandfather, mother, uncle, father and elder brother were heterozygous carriers with normal phenotype and no clinical symptoms associated with dopa responsive dystonia. Conclusion:The homozygous c. 353A>T variant of the GCH1 gene probably underlay the tetrahydrobiopterin deficiency in this pedigree of consanguineous marriage.
10.Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway
Liu SHULING ; Cheng FAFENG ; Ren BEIDA ; Xu WENXIU ; Chen CONGAI ; Ma CHONGYANG ; Zhang XIAOLE ; Tang FEIFEI ; Wang QINGGUO ; Wang XUEQIAN
Journal of Traditional Chinese Medical Sciences 2022;9(3):298-310
Objective:The Qinzhi Zhudan formula(QZZD)exhibits a prominent therapeutic effect in the treatment of vascular dementia(VaD).This study combined a network pharmacology approach and experimental validation to identify the underlying biological mechanism of QZZD against VaD.Methods:Male Wistar rats received bilateral common carotid artery occlusion(BCCAO)surgery,and after 4 weeks of intragastric administration of QZZD,the therapeutic effect was assessed using the Morris water maze test and cerebral blood flow(CBF)assessment.Hematoxylin and eosin staining,Nissl staining,and electron microscopy were used to measure the histopathological changes in the neurons of rats.The effect of QZZD treatment on hippocampal neurotransmitters was assessed by high-performance liquid chromatography with electrochemical detection and liquid chromatography mass spectrometry.Immunofluorescence was used to observe VaD-induced microglia activation.The inflammatory cytokine levels were assessed by enzyme linked immunosorbent assay.Western blot was used to examine the TNFR1-mediated TNF pathway,which was screened out by network pharmacology analysis.Results:QZZD treatment alleviated pathological changes and neuronal damage in VaD rats and atten-uated their cognitive impairment.In addition,QZZD increased CBF and the expression of acetylcholine and 5-hydroxytryptamine in the hippocampal region.Notably,QZZD inhibited microglial activation and the expression of IL-6 and TNF-a.Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1,NF-KBp65,p-ERK,TNF-α,and IL-6,which are related to the TNFR1-mediated TNF signaling pathway.Conclusion:QZZD clearly improved learning and memory function,reduced brain pathological damage,elevated CBF and hippocampal neurotransmitter levels,and alleviated neuroinflammation of VaD rats partly by inhibiting the TNFR1-mediated TNF pathway,indicating its potential value in the clinical therapy of VaD.

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