1.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
2.Randomized Double-blind Placebo-controlled Study on Clinical Efficacy and Mechanism of Shexiang Baoxinwan in Treating Stable Angina Pectoris Complicated with Anxiety and Depression in Coronary Artery Disease
Jie WANG ; Linzi LONG ; Zhiru ZHAO ; Feifei LIAO ; Jieming LU ; Tianjiao LIU ; Yuxuan PENG ; Hua QU ; Changgeng FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):159-169
ObjectiveTo evaluate the efficacy of Shexiang Baoxinwan in treating stable angina pectoris with Qi stagnation and blood stasis syndrome in patients with coronary artery disease (CAD) complicated with anxiety and depression and explore its underlying mechanisms. MethodsThis study employed a randomized, double-blind, and placebo-controlled clinical trial design. Patients admitted to the hospital were randomly assigned to the observation group and the control group, with 52 patients in each group. Patients in the observation and control groups received Shexiang Baoxinwan and placebo, respectively, both in combination with conventional Western medication. The dose was 45.0 mg, three times daily, for a total duration of eight weeks. The primary outcome was the Seattle Angina Questionnaire (SAQ) scores before and after treatment. Secondary outcomes included changes in traditional Chinese medicine (TCM) syndrome score, the patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7), inflammatory markers [interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), CD40, etc.], monoamine neurotransmitters [e.g., dopamine (DA)], vascular endothelial function markers [e.g., endothelin-1(ET-1)], adipokines, and ischemia-modified albumin (IMA). Adverse reactions were also recorded. ResultsA total of 92 patients completed the study, with 44 in the observation group and 48 in the control group. Compared with baseline, both groups showed significant decreases in PHQ-9, GAD-7, and TCM syndrome scores following treatment (P<0.05), along with a significant increase in SAQ scores (P<0.05). In the observation group, DA levels were significantly increased (P<0.05), while levels of IL-18, TNF-α, CD40, ET-1, and IMA were decreased (P<0.05). In contrast, the control group exhibited significantly increased CD40 levels (P<0.05). Compared with the control group after treatment, the observation group showed significant improvements in the SAQ dimensions of physical limitation, angina stability, treatment satisfaction, and disease perception, as well as in TCM syndrome score, PHQ-9 score, IL-18, CD40, ET-1, and IMA (P<0.05). No adverse reactions were observed in either group during treatment. ConclusionShexiang Baoxinwan can improve anxiety and depression, alleviate angina symptoms, and reduce TCM symptoms of Qi stagnation and blood stasis in CAD patients. The mechanism may involve anti-inflammation, improvement of vascular endothelial function, reduction of IMA, and increase of monoamine neurotransmitter levels.
3.Research hotspots of artificial intelligence in the field of spinal deformity:visual analysis
Guangyi TAO ; Linzi WANG ; Bin YANG ; Junqing HUANG
Chinese Journal of Tissue Engineering Research 2024;28(30):4915-4920
BACKGROUND:With the continuous improvement and progress of artificial intelligence technology in the treatment of spinal deformity,a large number of studies have been invested in this field,but the main research status,hot spots and development trends are still unclear. OBJECTIVE:To visually analyze the literature related to artificial intelligence in the field of spinal deformities by using bibliometrics,identify the research hotspots and shortcomings in this field,and provide references for future research. METHODS:The core database of Web of Science was used to search the articles related to artificial intelligence in the field of spinal deformities published from inception to 2023.The data were visually analyzed by Citespace 5.6.R5 and VOSviewer 1.6.19. RESULTS AND CONCLUSION:(1)A total of 165 papers were included,and the number of papers published in this field showed a fluctuating upward trend.The author with the largest number of articles is Lafage V,and the country with the largest number of articles is China.(2)Keyword analysis results show that adolescent scoliosis,deep learning,classification,precision and robot are the main keywords.(3)The in-depth analysis results of co-cited and highly cited articles show that artificial intelligence has three hotspots in the field of spinal deformities,including the use of U-shaped architecture(a mature mode of deep learning convolutional neural networks)to automatically measure imaging parameters(Cobb angle and accurate segmentation of paraspinal muscles),multi-view correlation network architecture(i.e.,spine curvature assessment framework),and robot-guided spinal surgery.(4)In the field of artificial intelligence treatment of spinal malformations,the mechanism research such as genomics is very weak.In the future,unsupervised hierarchical clustering and other machine learning techniques can be used to study the basic mechanism of susceptibility genes in the field of spinal deformities by genome-wide association analysis and other genomics research methods.
4.Incidence and risk factors of anastomotic leak after transanal total mesorectal excision in China: a retrospective analysis based on national database.
Lei GU ; Yong Bo AN ; Ming Yang REN ; Quan WANG ; Hong Yu ZHANG ; Gang YU ; Jian Zhi CHEN ; Miao WU ; Yi XIAO ; Zhi Cong FU ; Hong ZHANG ; Wei Dong TONG ; Dan MA ; Qing XU ; Hong Wei YAO ; Zhong Tao ZHANG
Chinese Journal of Gastrointestinal Surgery 2021;24(6):505-512
Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.
Adult
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Anastomotic Leak/etiology*
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Case-Control Studies
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China/epidemiology*
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Female
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Humans
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Incidence
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Laparoscopy
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Male
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Rectal Neoplasms/surgery*
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Rectum/surgery*
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Retrospective Studies
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Risk Factors
5.Expression of programmed death ligand 1 in rectal cancer and its significance
Guanghua MAO ; Jun WANG ; Linzi JIA ; Linxian CHENG ; Junhua LI ; Jingfang YAN ; Meiyan GAO ; Yingting LIANG
Cancer Research and Clinic 2021;33(11):840-843
Objective:To investigate the expression of programmed death ligand 1 (PD-L1) in rectal cancer tissues and the correlation of PD-L1 expression with clinicopathological characteristics and overall survival of patients.Methods:The clinical data of 200 newly treated rectal cancer patients in Shanxi Provincial Cancer Hospital from January 2014 to December 2015 were retrospectively analyzed. The expression of PD-L1 in rectal cancer tissues was detected by immunohistochemistry. The correlations of PD-L1 expression with gender, age, tumor T stage, lymph node metastasis, tumor differentiation, histological type, tumor TNM stage, neutrophil-to-lymphocyte ratio (NLR) and overall survival of patients were analyzed.Results:The positive expression rate of PD-L1 was 24% (48/200). The positive expression rate of PD-L1 was high in patients with lymph node metastasis and high NLR (≥ 3.5) (both P < 0.05). The 5-year overall survival rate in PD-L1-positive group was 42%, and the PD-L1-negative group was 59%, and the difference between the two groups was statistically significant ( P < 0.05). The results of multivariate analysis showed that lymph node metastasis ( HR = 3.456, 95% CI 2.148-5.556, P < 0.01), NLR ≥ 3.5 ( HR = 1.871, 95% CI 1.169-2.996, P = 0.009), and PD-L1-positive expression ( HR = 2.187, 95% CI 1.373-3.484, P = 0.001) were independent adverse influencing factors for the overall survival of rectal cancer patients. Conclusion:PD-L1 is highly expressed in rectal cancer tissues, and the positive expression of PD-L1 is associated with poor overall survival of patients.
6.Effects of Jinshuibao tablet on immune function and chemotherapy efficacy in patients with advanced lung squamous cell carcinoma
Linzi JIA ; Guanghua MAO ; Jun WANG ; Binbin SHAN ; Hongxia WANG
Cancer Research and Clinic 2020;32(9):637-641
Objective:To investigate the influence of Jinshuibao tablet on immune function, therapeutic efficacy and safety in treatment of advanced lung squamous cell carcinoma patients treated by chemotherapy.Methods:The clinical data of 124 patients with stage Ⅳ lung squamous cell carcinoma who were admitted to Shanxi Provincial Cancer Hospital from January 2015 to December 2017 were retrospectively analyzed, including 60 patients treated by Jinshuibao tablet combined with chemotherapy (the observation group) and 64 patients treated by chemotherapy alone (the control group). The changes of immune function, therapeutic effect, and side effects were compared between the two groups.Results:The percentage of CD4 + cells after treatment [(33.4±8.9)% vs. (45.5±11.8)%, t = 2.71, P < 0.05] and CD4 +/CD8 + (0.9±0.3 vs. 1.5±0.4, t = 3.31, P < 0.05) in the observation group was increased compared with that before treatment, CD8 + cells was decreased compared with that before treatment [(30.9±8.6)% vs. (21.1±8.1)%, t = 2.42, P < 0.05], interferon-γ (IFN-γ) [(7.7±2.8)% vs. (14.1±2.4)%, t = 2.74, P < 0.05] and interleukin-2 (IL-2) [(8.8±3.2)% vs. (12.7±1.6)%, t = 2.96, P < 0.05] was increased compared with that before treatment. The percentage of CD3 + cells [(57.9±8.2)% vs. (45.2±10.8)%, t = 2.70, P < 0.05], CD4 + cells [(32.9±9.0)% vs. (22.8±9.6)%, t = 3.19, P < 0.05], NK cells [(14.9±3.1)% vs. (9.3±1.4)%, t = 2.97, P < 0.05] in the control group was decreased compared with that before treatment. Tumor necrosis factor α (TNF-α) was decreased compared with that before treatment [(6.8±1.4)% vs. (4.3±0.5)%, t = 3.23, P < 0.05]. There was a statistically significant difference in the level of T-cell subsets of both groups after treatment (all P <0.05); and the level of CD3 +, CD4 +, CD4 +/CD8 +, NK cells in the observation group was higher than that in the control group; CD8 + cell in the observation group was lower than that in the control group. There was no statistical difference in the level of IFN-γ, IL-2, TNF-α of both groups before treatment (all P > 0.05); the level of IFN-γ, IL-2, TNF-α in the observation group was higher than that in the control group after treatment, and the difference was statistically significant of both groups (all P < 0.05). The total effective rate of the observation group was higher than that in the control group, and the difference was statistically significant [31.3% (20/64) vs. 48.3% (29/60), χ 2 = 4.538, P = 0.033]; and the disease control rate in the observation group was higher than that in the control [56.3% (36/64) vs. 71.7% (43/60), χ 2 = 5.276, P = 0.022]. There was no significant difference between the two groups in adverse reactions of chemotherapy (all P > 0.05). Conclusion:Jinshuibao tablet combined with chemotherapy can improve the immune function and the efficacy of chemotherapy for patients with advanced lung squamous cell carcinoma.
7.Association between ACTN3 gene R577X polymorphism and blood lipid levels in an elderly Chinese Han population in Rugao,China
Jianming SHI ; Linzi LI ; Hui ZHOU ; Zhengdong WANG ; Xuefeng CHU ; Yinsheng ZHU ; Xuejuan XIE ; Zuyun LIU ; Li JIN ; Xiaofeng WANG
Fudan University Journal of Medical Sciences 2017;44(4):476-482
Objective To explore the association between ACTN3 gene R577X polymorphism and serum lipid levels in an elderly Chinese Han population.Methods This study was based on the ageing arm of The Rugao Longevity and Ageing Study (RtLAS).Genotyping was performed by Taqman MGB method.Lipids includedtotal cholesterol (TC),triglyceride (TG),high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).Cut points of dyslipidemia were based on that reported in the NCEP ATPIII.We explored the associations between R577X polymorphism loci and dyslipidemia by using analysis of covariance and logistic regression analysis.Results Overall 1 618 samples was included (741 males and 877 females) in this study.Covariance analysis found that TC level of RR,XX and RX genotype in the general population were 1.34,1.37,1.43 mmol/L with an increasing trend (P =0.024);TC and LDL-C levels of RR,XX and RX genotype (TC:5.13,5.29,5.43 mmol/L,P =0.004;LDL-C:2.76,2.88,3.00 mmol/L,P =0.004) were significantly different in females.Logistic regression analysis showed that the increased copies of X allele were significantly associated with increased TC and LDL-C levels in the general population and females.For the general population,TC:OR=1.184,95%CI:1.030-1.361,P =0.018;LDL-C:OR =1.334,95%CI:1.101-1.588,P=0.003;For females,TC:OR=1.332,95% CI:1.102-1.616,P =0.003;LDL-C:OR =1.549,95 %CI:1.208-1.986,P =0.001.After adjusting for other covariates,the above associations remained significant.Conclusions ACTN3 gcnc R577X polymorphism is associated with plasma TC and LDL-C levels in elderly woman of Han populations in Rugao,China.
8.Effect of pyrroloquinoline quinone on learning and memory ability of apolexis rats
Liang TANG ; Linzi LI ; Wenmin HU ; Zhihang HU ; Ling ZHANG ; Lijing ZHANG ; Song MEI ; Jianguo CHEN ; Dongying LIU ; Zhen LIU ; Yin WANG
Chinese Journal of Food Hygiene 2017;29(4):407-411
Objective This study aimed to investigate the role of pyrroloquinoline quinone (PQQ) in repairing oxidative nerve cells,and to study the antioxidant capacity of PQQ on the oxidative damage of rats caused by apolexis,as well as the effects on learning and memory abilities of apolexis rats.Methods Oxidative damage of PC12 was induced by H2O2,and the repairing rate of PQQ on oxidative PC12 cells was tested by methylthiazolyldiphenyl-tetrazolium bromide assay kit.The 18-month-old male SD rats were administered PQQ (0,10,20,40 mg/kg).After 4 weeks,Morris water maze test was used to test the learning and memory ability.After 6 weeks,serum and brain tissue related indicators and antioxidant capacity were recorded.Results The survival rate of PC12 cells increased from 59.1% to 90.5% with 200 nmol/L PQQ.Compared with the apolexis model group,the latency of the PQQ group (20,40 mg/kg) was shortened in the Morris water maze experiment,the swimming distance was reduced,pass-through counts were increased,and the first secure platform pass-through was reduced.Meanwhile,the levels of malondialdehyde and lipofuscin in serum and brain tissue of PQQ group decreased,the levels of superoxide dismutase,glutathione peroxidase vitality,antioxidant capacity of PQQ group (20,40 mg/kg) were enhanced.Conclusion PQQ could repair the oxidative damage of nerve cells,and it was confirmed that PQQ could play the same antioxidant effect in body and brain,and increase the learning and memory ability of apolexis rats.
9.Light transmittance aggregometry with non-adjusted PRP is more suitable for clinical laboratory =monitoring antiplatelet therapy
Linzi MIAO ; Jianzhong WANG ; Hui YUAN ; Jiaying YUAN ; Xiuqing ZHAO ; Ying XING
Chinese Journal of Laboratory Medicine 2013;(5):405-409
Objective In this study,maximum platelet aggregation rate of Light transmittance aggregometry (LTA) for coronary heart disease(CHD) patients taking antiplatelet drug and patients without antiplatelet therapy was measured in non-adjusted and platelet count-adjusted platelet-rich plasma (PRP).The aim of this study is to compare which method is superior in evaluation of antiplatelet drug effect.Methods This is a methodology comparative research.560 CHD outpatients and inpatients that visited Beijing Anzhen Hospital of the Capital University of Medical Sciences from May to June,2012 were chosen,who were treated with aspirin monotherapy,or patients on combination therapy with aspirin and clopidogrel,as well as patients without antiplatelet therapy.LTA was performed in non-adjusted (improved method) and platelet count (200 × 109/L)-adjusted PRP (original method),using 6 μmol/L adenosine diphosphate (ADP) and 0.5 mmol/L arachidonic acid (ARA) as agonists.The maximum aggregation rates in 5 min were detected,and consistency and differences of the two methods were compared.Results There is no statistically significant correlation between maximum aggregation rate and platelet count in PRP with 6 μmol/L ADP or 0.5 mmol/L ARA as agonists in all subgroups including aspirin monotherapy,combination therapy with aspirin and clopidogrel and patients without antiplatelet therapy (-0.21 ≤ r ≤0.111,P > 0.05).The maximum aggregation rate using ADP as agonists in original method is decreased compared with improved method,there is statistically significant difference in all subgroups including patients without antiplatelet therapy,aspirin monotherapy,combination therapy with aspirin and clopidogrel less than one week and more than one week.The variability of platelet aggregation rate using ADP as agonists with improved method is lower than that with original method in all subgroups.Yet the maximum aggregation rates using ADP as agonists with improved method and original method correlate well with each other in all subgroups (r =0.78,0.73,0.40,0.71,P <0.01).In the subgroup of subjects without antiplatelet therapy using ARA as agonist,platelet aggregation rate is decreased in original method compared with improved method,there is statistically significant difference,and the variability of the aggregation rate with improved method is also lower than that with original method,ranging from 62%-98% relative to 5%-89%.The decrease of aggregation rate using ARA as agonist for patients taking antiplatelet drug compared with patients without antiplatelet therapy can be detected both with improved method and original method.Conclusion Non-adjusted PRP in LTA is more convenient and time-saving,and it also means less effects on platelet in vitro.Therefore,non-adjusted PRP is more suitable for monitoring efficacy of antiplatelet therapy in clinical laboratory.
10.Analysis of parkin gene mutations in Han Chinese with sporadic early-onset parkinsonism in southern China
Liluo NIE ; Jifeng GUO ; Hainan ZHANG ; Xuewei ZHANG ; Lei WANG ; Linzi LUO ; Lu SHEN ; Hong JIANG ; Kun XIA ; Beisha TANG ; Xinxiang YAN
Chinese Journal of Neurology 2010;43(10):692-696
Objective To investigate the spectrum and features of parkin gene mutations in Chinese patients with sporadic early-onset Parkinsonism (EOP) in southern China.Methods All 156 Han Chinese patients with sporadic EOP were screened for mutations in parkin gene using SYBR Green Ⅰ Real-time PGR combined with sequencing of the entire coding region of the gene.Results Nineteen cases carried parkin mutations, including 2 homozygous, 2 compound heterozygous and 15 heterozygous mutations.Seventeen parkin gene rearrangement mutations ( 12 exon deletions and 5 exon duplications) and three small sequence mutations (ⅣS9 + 18C > T,c.202-203delAG and c.813delT) were identified.The c.813delT is a novel mutation.The segment between exon 1 and 7 are mutational hot spot.Cases with parkin mutations showed no difference in initial symptoms, cardinal symptoms and disease severity, compared with cases without parkin mutations.But patients with parkin mutations showed significant earlier onset age ( ( 40.9 ± 6.8 ) years vs (35.5 ± 10.0) years, Z = -2.271, P <0.05) and longer disease duration ( (4.4 ±3.6) years vs (7.6 ±4.0) years,Z = - 3.680, P < 0.05 ) than those without parkin mutation.Conclusions The frequency of parkin gene mutation was 12.18% in Han Chinese patients with sporadic EOP.Rearrangement mutation may be the predominant type of mutations.The exon deletion is a main mutation style.The sequence fragment between exon 1 and 7 of the parkin gene are mutational hot spots.There were no significant differences in clinical features between cases with parkin mutation and those without.However, our patient with parkin mutations showed a significantly earlier onset age, longer disease duration and slower progression than those without parkin mutation.

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