1.Evidence-based study on postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor
Xiandan LUO ; Yanli LU ; Yihang WU ; Yanxiang GUO ; Xiaoyi YAN ; Yongchao HUO ; Hui YAN ; Zhenjiang YANG ; Hongliang ZHANG
China Pharmacy 2025;36(18):2328-2333
OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed, Embase, Web of Science, CBM, VIP, Chinese Medical Journal Data, Wanfang Data, and CNKI, as well as the official websites of GIN, NICE, Medlive, AHRQ, CSCO, ASCO, and NCCN. The search period was from the establishment of the databases/websites to March 10, 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows: scope and purpose of 85.07%, participants of 47.92%, rigor of development of 57.49%, clarity of presentation of 88.02%, applicability of 8.20%, and independence of 53.39%. Among them, 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants, rigor of development, and independence of the guidelines/consensuses in China were significantly lower than foreign countries (P<0.05); the scores for participants and rigor of development of the guidelines were significantly higher than consensuses (P<0.05). The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients;platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients; non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants, rigor of development, and independence, to recommend treatment plans based on the different stages of ovarian cancer, and develop guidelines/consensuses that align with China’s national conditions.
2.Effect of Coptidis Rhizoma-Fermentum Rubrum on Non-Alcoholic Fatty Liver Disease in Mice Based on Nrf2/GPX4 Ferroptosis Axis
Yang YANG ; Xiaobo ZHANG ; Yong ZHANG ; Fuming LU ; Yaqi LUO ; Xiaoyi WU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(20):30-36
ObjectiveTo observe the effects of Coptidis Rhizoma-Fermentum Rubrum on non-alcoholic fatty liver disease (NAFLD) in mice and explore its possible mechanisms. MethodSixty male SPF C57BL/6J mice were randomly divided into six groups: control group, model group, low-, medium-, and high-dose Coptidis Rhizoma-Fermentum Rubrum group (0.75, 1.5, 3 g·kg-1), and metformin group (0.075 g·kg-1), with 10 mice in each group. NAFLD mouse models were induced by high-fat diet feeding for 24 weeks. The low, medium, and high-dose Coptidis Rhizoma-Fermentum Rubrum groups were administered corresponding doses of Coptidis Rhizoma-Fermentum Rubrum by gavage, while the control and model groups received an equivalent amount of saline for four weeks. Serum total cholesterol (TC), triglycerides (TG), free fatty acids (FFA), and liver function markers including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using an automatic biochemical analyzer. Hematoxylin-eosin (HE) and oil red O staining were used to detect liver lipid deposition, and Prussian blue staining was used to measure liver ferrous ion levels. Western blot was performed to detect the expression of key proteins in the nuclear factor erythroid-2-related factor 2 (Nrf2)-glutathione peroxidase 4 (GPX4) axis. ResultAfter 24 weeks of high-fat feeding, compared with the control group, the model group showed significant increases in body weight, liver weight and liver index, and serum lipid levels (P<0.01), as well as substantial hepatic lipid deposition with marked steatosis. Compared with the model group, Coptidis Rhizoma-Fermentum Rubrum intervention reduced body weight (P<0.01), liver weight and liver index (P<0.01), and serum lipid levels (P<0.05, P<0.01), improved liver function (P<0.01), and decreased hepatic lipid deposition, with the low-dose Coptidis Rhizoma-Fermentum Rubrum group showing the best effect. Western blot results showed that compared with those in the control group, the expression levels of Nrf2, heme oxygenase-1 (HO-1), kelch-like ECH-associated protein 1(Keap1), and GPX4 proteins in the model group were decreased (P<0.05, P<0.01). Compared with the model group, Coptidis Rhizoma-Fermentum Rubrum increased the expression levels of these proteins (P<0.05, P<0.01). ConclusionCoptidis Rhizoma-Fermentum Rubrum can alleviate fatty liver in mice, improve liver function, and reduce hepatic lipid deposition, possibly by regulating the Nrf2/GPX4 ferroptosis axis.
3.Value of 18F-PSMA-1007 PET/CT-based radiomics model for differential diagnosis between prostate cancer and benign prostatic hyperplasia
Liang LUO ; Ruxi CHANG ; Yunxuan LI ; Jungang GAO ; Xiang LIU ; Xiaoyi DUAN
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(2):80-85
Objective:To evaluate the value of prostate specific membrane antigen (PSMA) PET/CT-based radiomics models in differentiation between prostate cancer and benign prostatic hyperplasia (BPH).Methods:Data from 50 patients with prostate cancer (age: (70.0±8.8) years) and 25 patients with BPH (age: (66.9±9.4) years) who underwent 18F-PSMA-1007 PET/CT imaging and prostate biopsy in the First Affiliated Hospital of Xi′an Jiaotong University from May 2020 to September 2022 were retrospectively collected. Patients were divided into the training set ( n=53) and test set ( n=22) in the ratio of 7∶3 by using random seed number. The ROIs were delineated based on PET and CT images, and radiomics features were extracted respectively. Feature selection was performed using the minimum redundancy and maximum relevance (mRMR) and the least absolute shrinkage and selection operator (LASSO) algorithm. PET and PET/CT radiomics models were generated using logistic regression. ROC curve analysis was employed for model evaluation. In addition, comparisons of the 2 radiomics models with parameters including the ratio of free prostate specific antigen (fPSA)/total prostate specific antigen (tPSA), PET metabolic parameters, as well as prostate cancer molecular imaging standardize evaluation (PROMISE) were conducted (Delong test). Results:A total of 7 features were included in the PET radiomics model, and 3 CT-based features and 4 PET-based features were included in the PET/CT radiomics model. The AUCs of PET and PET/CT radiomics models in the training set and test set were 0.941, 0.914 and 0.965, 0.914, respectively, which were higher than those of fPSA/tPSA (0.719 and 0.710), SUV max(0.748 and 0.800), peak of SUV (SUV peak, 0.722 and 0.771), metabolic tumor volume (MTV, 0.640 and 0.595), total lesion uptake (TLU, 0.525 and 0.476) and PROMISE (0.644 and 0.667)[ z values for the training set: from -6.26 to -3.13, all P<0.01; z values for the test set: from -3.16 to -1.08, P>0.05 (fPSA/tPSA, SUV max, SUV peak) or P<0.05 (MTV, TLU, PROMISE)]. The differential diagnostic accuracy, sensitivity and specificity of PET and PET/CT radiomics models in the test set were 86.36%(19/22), 13/15, 6/7 and 90.91%(20/22), 15/15, 5/7, respectively. Conclusion:Compared with the clinical and PET parameters, PSMA PET/CT-based radiomics model can further improve the efficiency of differential diagnosis between prostate cancer and BPH.
4.Cynaroside regulates the AMPK/SIRT3/Nrf2 pathway to inhibit doxorubicin-induced cardiomyocyte pyroptosis
ZOU HAI ; ZHANG MENGYU ; YANG XUE ; SHOU HUAFENG ; CHEN ZHENGLIN ; ZHU QUANFENG ; LUO TING ; MOU XIAOZHOU ; CHEN XIAOYI
Journal of Zhejiang University. Science. B 2024;25(9):756-772
Doxorubicin(DOX)is a commonly administered chemotherapy drug for treating hematological malignancies and solid tumors;however,its clinical application is limited by significant cardiotoxicity.Cynaroside(Cyn)is a flavonoid glycoside distributed in honeysuckle,with confirmed potential biological functions in regulating inflammation,pyroptosis,and oxidative stress.Herein,the effects of Cyn were evaluated in a DOX-induced cardiotoxicity(DIC)mouse model,which was established by intraperitoneal injections of DOX(5 mg/kg)once a week for three weeks.The mice in the treatment group received dexrazoxane,MCC950,and Cyn every two days.Blood biochemistry,histopathology,immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and western blotting were conducted to investigate the cardioprotective effects and potential mechanisms of Cyn treatment.The results demonstrated the significant benefits of Cyn treatment in mitigating DIC;it could effectively alleviate oxidative stress to a certain extent,maintain the equilibrium of cell apoptosis,and enhance the cardiac function of mice.These effects were realized via regulating the transcription levels of pyroptosis-related genes,such as nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),caspase-1,and gasdermin D(GSDMD).Mechanistically,for DOX-induced myocardial injury,Cyn could significantly modulate the expression of pivotal genes,including adenosine monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),sirtuin 3(SIRT3),and nuclear factor erythroid 2-related factor 2(Nrf2).We attribute it to the mediation of AMPK/SIRT3/Nrf2 pathway,which plays a central role in preventing DOX-induced cardiomyocyte injury.In conclusion,the present study confirms the therapeutic potential of Cyn in DIC by regulating the AMPK/SIRT3/Nrf2 pathway.
5.Exploring the Intervention Mechanism of Zishen Jianpi Huayu Tablets on Diabetic Retinopathy Based on Network Pharmacology,Molecular Docking and Experimental Validation
Haitong FENG ; Yulin QI ; Yawen FENG ; Jia ZHOU ; Yingzi LUO ; Xiaoyi YU
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(8):1197-1205
Objective To explore the mechanism of Zishen Jianpi Huayu Tablets(Corni Fructus,Notoginseng Radix et Rhizoma,Astragali Radix,Puerariae Lobatae Radix,Spatholobi Caulis,Rehmanniae Radix)in the treatment of diabetic retinopathy(DR)by means of network pharmacology and molecular docking technique,and verified by in vitro experiments.Methods The active components of Zishen Jianpi Huayu Tablets and their corresponding target proteins were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the BATMAN-TCM database.Drug target proteins were converted to their corresponding gene names through the UniProt database.DR-related targets were searched using"diabetic retinopathy"as a keyword in GeneCards,DrugBank,OMIM,and TTD databases.Common targets between the disease and the drug were identified using the Venny tool.These common targets were analyzed using the String database,a protein-protein interaction(PPI)network was constructed.Topological heterogeneity analysis was performed using Cytoscape 3.9.1 to select core targets and create a PPI network diagram.These common targets were entered into the Metascape database for Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis to identify potential action pathways.Molecular docking of the main active components and core targets was performed using Auto Dock tools software,followed by further experimental validation.The CCK-8 assay was used to assess the effect of Zishen Jianpi Huayu Tablet medicated serum on the cell viability of Human Retinal Microvascular Endothelial Cells(HRmECs)under high glucose conditions,and RT-qPCR was used to measure the expression of IL-1β,AKT1,VEGFA,and TP53 mRNA in HRmECs.Results(1)The effective components and corresponding target proteins of Zishen Jianpi Huayu Tablets were screened by Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)and BATMAN-TCM database.The disease-related targets of DR were searched by GeneCards,OMIM and TTD databases.The use of VENNY platform for drug active components target and DR disease-related target to take intersection(common target),that is,Zishen Jianpi Huayu Tablets in the treatment of DR potential target.The network of"drugs-active components-common targets"was constructed to screen out the key active components of Zishen Jianpi Huayu Tablets in the treatment of DR.Import the common target into STRING database,obtain the PPI network relationship,and screen out the core target.Metascape platform was used to analyze the GO function and KEGG pathway enrichment of the common targets.The key active components and core targets were verified by Autodock 4 software for molecular docking.(2)The drug-containing serum and blank serum of Zishen Jianpi Huayu Tablets was prepared.Human retinal microvascular endothelial cells(HRmECs)were randomly divided into 5 groups:the control group(low-sugar DMEM medium+10%blank serum),high-glucose group(high-sugar DMEM medium+10%blank serum)and Zishen Jianpi Huayu Tablets containing low-,medium-and high-dose serum(high-sugar DMEM medium+10%low-,medium-and high-dose drug containing serum)were detected after 48 hours of culture.The proliferative activity of HRmECs cells was detected by CCK-8 method,and the mRNA expressions of IL-1β,AKT1,VEGFA and TP53 in HRmECs cells were detected by RT-qPCR method.Conclusion Zishen Jianpi Huayu Tablets may act on core targets such as IL-1β,IL-6 and VEGFA,as well as key pathways such as NF-κB signaling pathway,AGE-RAGE signaling pathway and PI3K-AKT pathway through various active components such as quercetin,kaempferol and rehmannia flavonoids,so as to play a therapeutic role in DR.
6.Detection of aqueous humor cytokines in diabetic retinopathy and its clinical significance
Yue TENG ; Xiaoting ZENG ; Yingzi LUO ; Ruting ZHANG ; Junhui LI ; Hong LIU ; Yan YANG ; Xiaoyi YU
Chinese Journal of Experimental Ophthalmology 2023;41(1):55-62
Objective:To detect the concentration of various cytokines in aqueous humor of patients with diabetes retinopathy (DR) with Luminex liquid chip, and analyze the relationship between the cytokines and the occurrence and development of DR.Methods:A cross-sectional study was conducted.Sixty-three DR patients (97 eyes) treated with anti-vascular endothelial growth factor (VEGF) drugs in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from March 1, 2019 to December 31, 2019 were enrolled as DR group, including 38 nonproliferative DR (NPDR) eyes in NPDR group and 59 proliferative DR (PDR) eyes in PDR group, 39 eyes in photocoagulation group and 58 eyes in non-photocoagulation group.Twenty-seven patients (31 eyes) hospitalized for cataract surgery at the same time were collected as the control group.Aqueous humor was extracted during the operation, and Luminex liquid chip was used to detect the concentrations of vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, angiopoietin-like protein 4 (ANGPTL4), interleukin-6 (IL-6), IL-8, IL-1β, monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in aqueous humor.The concentrations of various cytokines of different groups were compared, and the correlation among various aqueous humor cytokines was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of First Affiliated Hospital of Guangzhou University of Chinese Medicine (No.Y[2019]230). Written informed consent was obtained from each patient.Results:The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in DR group were significantly higher and the concentration of IL-1β was significantly lower than those of control group ( Z=-4.747, -5.164, -3.373, -8.062, -4.535, -5.954, -5.098, -3.228, -5.954, all at P<0.01). The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8 and MCP-1 of the photocoagulation and non-photocoagulation groups were higher and the concentration of IL-1β was significantly lower than those in the control group (all at P<0.017). The concentration of ICAM-1 in the photocoagulation group was significantly higher than that in the control group ( P<0.017). The concentrations of PLGF, PDGF-AA and ANGPTL4 of PDR group were higher than those of NPDR group, and the differences were statistically significant ( Z=-2.291, -3.396, -2.276, all at P<0.05). VEGF-A was positively correlated with the other cytokines except ICAM-1 ( rs=0.237-0.540, all at P<0.05). ANGPTL4 was positively correlated with the other cytokines except IL-1β ( rs=0.361-0.733, all at P<0.01). Conclusions:The occurrence and development of DR are closely related to VEGF family, PDGF family, ANGPTL family and inflammatory factors.The concentrations of PLGF, PDGF-AA and ANGPTL4 are higher in PDR eyes.There are close and complex relationships among a variety of cytokines in the eyes of DR patients.
7.Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii.
Lichan TU ; Xinbo CAI ; Yifeng ZHANG ; Yuru TONG ; Jian WANG ; Ping SU ; Yun LU ; Tianyuan HU ; Yunfeng LUO ; Xiaoyi WU ; Dan LI ; Luqi HUANG ; Wei GAO
Acta Pharmaceutica Sinica B 2022;12(6):2923-2933
Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids, but there are few studies on the origins of these diterpenoids in its secondary metabolism. Here, we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes (Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions. We further revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago (MYA) by whole-genome triplication (WGT), transposon mediation, and tandem duplication, followed by functional divergence. We first demonstrated that four key amino acids in the sequences of TwCPS3, TwCPS5, and TwCPS6 were altered during evolution, leading to their functional divergence and the formation of diterpene secondary metabolites. Then, we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids. Finally, we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T. wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase (TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event. Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T. wilfordii.
8.Biological specificity of 2019 novel coronavirus 614D and 614G pseudovirus
Fenlian MA ; Xiaoyi LUO ; Chao WANG ; Jingdong SONG ; Zhiping XIE ; Shanshan CONG ; Yiman HUANG ; Lishu ZHENG
Chinese Journal of Experimental and Clinical Virology 2022;36(4):397-401
Objective:To construct 2019 novel coronavirus (2019-nCoV) 614D and 614G pseudovirus by HIV lentivirus packaging system and explore their biological specificity.Methods:The recombinant expression plasmids pCDNA3.1-614D and pCDNA3.1-614G were transiently cotransfected with psPAX2 and pLenti CMV Puro LUC into 293T cells respectively. After 72 hours, the supernatant was collected and ultracentrifuged with 20% sucrose cushion. The titer, morphology, protein expression and neutralizing activity of pseudovirus were determined.Results:S protein specific fluorescence was detected by indirect immunofluorescence test, Western blot analysis showed S protein was expressed, and the spike of pseudovirus was observed under transmission electron microscope. The titers of pseudovirus 614D and 614G were 1.12×10 4 and 2.52×10 4 TCID 50/ml, respectively. The pseudovirus 614D and 614G could be neutralized by S rabbit polyclonal antibody, indicating that the pseudovirus has high specificity. Conclusions:In this study, 2019-nCoV 614D and 614G pseudovirus was successfully constructed, which laid the foundation for the establishment of in vitro neutralizing antibody detection platform based on pseudovirus.
9.Clinical characteristics and prenatal diagnosis of fetuses with sex chromosomal aneuploidies detected by non-invasive prenatal testing during early and midterm pregnancies.
Xiaojin LUO ; Yanyun GUO ; Fengxiang WEI ; Liang HU ; Yuanyuan PEI ; Xiaoyi CONG ; Xiaoyi LIU ; Jing CHEN ; Gaochi LI ; Hanbiao CHEN ; Li GUO ; Zheng CHEN
Chinese Journal of Medical Genetics 2021;38(4):321-324
OBJECTIVE:
To analyze the indication, karyotyping result, ultrasound finding, pregnancy decision and follow-up of fetuses with sex chromosome aneuploidies (SCA) detected by non-invasive prenatal testing (NIPT) during early and midterm pregnancies.
METHODS:
The results of 225 singleton pregnancies with fetal SCA detected by NIPT were reviewed and analyzed.
RESULTS:
The 225 cases included 45,X (n=37), 47,XXY (n=74), 47,XXX (n=50), 47,XYY (n=56) and mosaicisms (n=8), among which 121 (53.8%) have opted to terminate the pregnancy, including 45,X (n=31), 47,XXY (n=61), 47,XXX (n=14), 47,XYY (n=12) and 3 mosaicisms. The remainder 104 (46.2%) have elected to continue with the pregnancy, among which three have opted to terminate due to abnormalities detected by ultrasonography, and two had spontaneous abortions.
CONCLUSION
NIPT as a first-tier screening method can effectively detect fetal trisomies 21, 13 and 18 as well as SCA. The types of fetal SCA and presence of ultrasound abnormalities are critical factors for the termination of pregnancy.
Aneuploidy
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Down Syndrome
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Female
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Fetus
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Humans
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Pregnancy
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Prenatal Diagnosis
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Sex Chromosome Aberrations
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Trisomy
10.Short-term prognostic factors for Guillain-Barré syndrome in children
Jiayu HONG ; Xiaoyi LI ; Hongyuan DAI ; Na WANG ; Can LUO ; Long ZHENG ; Daokai GONG ; Ruiling ZHOU ; Wenjing LUO ; Bo HU ; Shuping LIU ; Jiajia YAO ; Zuneng LU
Chinese Journal of Neuromedicine 2020;19(5):504-507
Objective:To explore the short-term prognostic factors for Guillain-Barré syndrome (GBS) in children.Methods:The clinical data of children with GBS from 24 hospitals in 10 provinces/municipalities/autonomous regions in southern China (south of Huaihe River) from January 1, 2013 to September 30, 2016 were retrospectively analyzed. The factors affecting the short-term prognoses of children were explored.Results:In these 78 children (50 males and 28 females), the average age was 9.53±5.44 years, and 19 were under 5 years old. Fifty children had history of prodromal events; 28 children had cranial nerve involvement, and 22 had autonomic nerve involvement. Five children needed assisted respiration, and one died during hospitalization. There was no statistically significant difference in percentage of children having poor short-term prognosis (scores of Hughes GBS disability scale≥3 at discharge) between children with different ages, children having different days from onset to admission, children with different clinical classifications or electrophysiological classifications, children with different treatment plans, children having presence or absence of prodromal events, children having presence or absence of cranial nerve involvement ( P>0.05). The proportion of children having poor short-term prognosis in children with autonomic nerve involvement was significantly higher than that of children without autonomic nerve involvement (31.8% vs. 10.7%, P<0.05). Conclusion:The short-term prognosis of children with autonomic nerve involvement is poor.

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