1.Based on Network Pharmacology and Experimental Verification to Explore the Mechanism of Yangxin Decoction Anti-atherosclerosis
Haiquan HUANGFU ; Huichun HUANG ; Xiaoming SHANG ; Zhichao HUANG ; Weiqian LIAO ; Hairui YU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(4):1070-1079
Objective Based on network pharmacology and in vivo experiments,to explore the mechanism of Yangxin Decoction in treating arterial atherosclerosis.Methods In the network pharmacology part,TCMSP database is used to screen the drug active ingredients and corresponding targets of Yangxin Decoction,Gene Cards,DisGeNet,OMIM,TTD database is used to screen atherosclerosis disease targets,the Evenn platform for interactive mapping to obtain drug disease intersection targets.Cytoscape 3.7.2 software is used to build a drug active ingredient core target disease interaction network diagram,The intersection target points are imported into STRING database to obtain PPI network diagram,and the Cytascape software is used for visualization processing.The metascape v3.5 platform is used for GO and KEGG enrichment analysis,and the micro-signal platform is used for visualization processing.In vivo experiment:ApoE-/-mice established atherosclerosis animal models through high-fat diet.The model mice were randomly divided into model group(Model),low-dose Yangxin Decoction group(YXT-L),and high-dose Yangxin Decoction group(YXT-H).C57BL/6 mice were taken as the control group,YXT-L group and YXT-H group were respectively given 2.6 g·kg-1·d-1 and 5.2 g·kg-1·d-1 of Yangxin Decoction extract aqueous solution,and the control group and model group were given equal volume distilled water for 4 weeks.Oil red O staining was used to observe the plaque area of aortic sinus,and ELISA was used to detect serum IL-6 and IL-1β,Caspase-3,VEGF levels,TG,TC,LDL-C,HDL-C levels of blood lipids detected by automatic biochemical instrument,and NF-κB p65,TNF-α,IKKβ Protein expression of aorta detected by Western blot.Results Network pharmacology:105 active ingredients of Yangxin Decoction were screened out,including 535 corresponding targets,4921 atherosclerotic disease targets,162 drug disease intersection targets,and the top 10 targets include AKT1,TNF,IL-6,VEGFA,IL-1β,TP53,JUN,CASP3,PPARG,PTGS2.A total of 2224 items were obtained from and GO analysis,including 1946 biological processes,100 cell components and 178 molecular functions.A total of 216 signal pathways were obtained by KEGG signal pathway enrichment analysis,mainly involving fluid shear stress,atherosclerosis,NF-κB signaling pathway,cAMP signaling pathway,diabetes cardiomyopathy,cysteine and methionine metabolism,VEGF signaling pathway,calcium signaling pathway,etc.In vitro experiment:Yangxin Decoction reduces serum TG,TC,LDL-C in ApoE-/-atherosclerosis mice in a dose-dependent manner,increases HDL-C level,reduces aortic sinus plaque area,and reduces serum IL-6,IL-1β,Caspase-3 and VEGF level;Inhibition of aortic NF-κB p65,TNF-α,IKKβ Protein expression.Conclusion Yangxin Decoction may inhibit TNF-α/IKKβ/NF-κB signaling pathway plays an anti-atherosclerosis role by regulating lipid metabolism,inhibiting inflammatory reaction,regulating cell apoptosis,etc.
2.Analysis on constructing a risk prediction model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery based on decision tree method
Dan WANG ; Zijuan ZHANG ; Huichun YANG ; Meili LIANG ; Lingzhi ZHENG
Chinese Journal of Endocrine Surgery 2023;17(3):323-326
Objective:The decision tree Chi-square automatic interactive detection (CHAID) algorithm and binary Logistic regression analysis were used to construct the risk prediction model of premature ovarian failure (POF) in patients with uterine fibroids complicated with hypertension after surgery, and the results of the risk prediction model were compared and analyzed.Methods:Patients with uterine fibroids complicated with hypertension admitted to Taizhou Hospital of Zhejiang Province from Jan. 2019 to Sep. 2022 were retrospectively analyzed as the research objects. CHAID algorithm and Logistic regression analysis were used to establish risk prediction models, respectively. The area under the curve (AUC) of receiver operating characteristic curve (ROC) was used to compare and evaluate the prediction effects of the two models.Results:A total of 860 patients were collected, including 56 patients with premature ovarian function failure after operation, and the incidence of premature ovarian function failure was 6.51%. CHAID method and Logistic regression analysis showed that uterine myoma surgery, hypertension, smoking or passive smoking, family history of premature ovarian failure, sleep status, physical exercise and history of induced curettage were important influencing factors of premature ovarian failure. The accuracy of risk prediction of decision tree model was 88.2%, and the fitting effect of the model was good. The Logistic regression model Hosmer-Leme-show goodness of fit test showed that the model fit was good. The AUC of Logistic regression model was 0.893 (95% CI: 0.862-0.899), and the AUC of decision tree model was 0.882 (95% CI: 0.856-0.899). The predictive value of the two models was moderate, and there was no significant difference between them ( Z=0.254, P>0.05) . Conclusions:The combination of decision tree and Logistic regression model can find the influencing factors of premature ovarian function failure in patients with uterine fibroids complicated with hypertension after operation from different levels, and the relationship between the factors can be more fully understood. The establishment of a risk model for premature ovarian function failure in patients with uterine fibroids complicated with hypertension after surgery can provide a reference for postoperative intervention in patients with uterine fibroids complicated with hypertension, and more effectively help patients actively prevent and slow down the occurrence and development of POF.
3.Correlations of transglutaminase 2 expression in peripheral blood mononuclear cells with relevant inflammatory factors and disease severity in patients with atopic dermatitis
Litian QU ; Jincong CHEN ; Bo CHENG ; Huichun SU
Chinese Journal of Dermatology 2023;56(7):651-656
Objective:To determine the expression of transglutaminase 2 (TGM2) in peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD), and to analyze its correlation with AD-related inflammatory factors and disease severity.Methods:A total of 29 AD patients and 15 healthy controls were collected from the First Affiliated Hospital of Fujian Medical University from July 2020 to January 2021. Ten milliliters of peripheral blood samples were collected from each subject, so was the clinical information, including age, gender, course of disease, eosinophil counts, basophil counts, total IgE levels, Scoring AD index (SCORAD), etc. PBMCs were isolated by density gradient centrifugation. Fluorescence-based quantitative PCR was performed to determine the mRNA expression of TGM2 and AD-related inflammatory factors (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, IL-13, IL-17, thymic stromal lymphopoietin [TSLP], P2RX7 [purinergic receptor P2X, ligand-gated ion channel, 7], etc.) in PBMCs from 29 AD patients and 15 healthy controls, and flow cytometry to determine TGM2 protein expression on PBMCs. Mann-Whitney U test was used to analyze differences between groups, and Spearman correlation analysis to evaluate the correlation. Results:The relative mRNA expression of TGM2 in PBMCs did not differ between the AD group and control group ( M[ Q1, Q3]: 0.509 [0.325, 0.958] vs. 0.475 [0.328, 1.051], U = 210.50, P = 0.872). Compared with the control group, the AD group showed significantly decreased IL-4 mRNA expression (0.171[0.049, 0.449] vs. 0.824 [0.397, 1.378], P < 0.001), but significantly increased mRNA expression of IL-8 and IL-13 ( P = 0.011, 0.006, respectively). Spearman correlation analysis showed that the mRNA expression level of TGM2 in PBMCs was positively correlated with the mRNA expression levels of IL-4 and P2RX7 in the AD group ( rs = 0.42, 0.40, P = 0.024, 0.034, respectively), while there were no correlations between TGM2 mRNA expression and AD severity-related indicators (all P>0.05), such as age (21[16, 29] years), course of disease (4[1,10] years), eosinophil counts (0.33[0.18, 0.65] × 10 9/L), basophil counts (0.04[0.03, 0.06] × 10 9/L], SCORAD scores (60.5[46.98, 66.13] points), and serum total IgE levels (373 [40, 1 815] IU/ml). The relative protein expression levels of TGM2 on the surface of PBMCs did not differ between the AD group and control group (54.9 [47.6, 62.8] vs. 55.55 [51.5, 60.25], U = 112.00, P = 0.922) ], and no correlations were observed between the protein expression of TGM2 on PBMCs and AD severity-related indicators in the AD group (all P > 0.05) . Conclusion:No significant differences were observed in TGM2 mRNA expression in PBMCs or TGM2 protein expression on the surface of PBMCs between the AD patients and healthy controls, and there were no correlations between the TGM2 mRNA and protein expression and AD severity.
4.Clinical characteristics and genetic variant analysis of a child with Snijders Blok-Campeau syndrome.
Yuke LI ; Xiaona WANG ; Mengyuan LIU ; Yang GAO ; Baiyun CHEN ; Daoqi MEI ; Huichun ZHANG ; Chao GAO
Chinese Journal of Medical Genetics 2023;40(4):402-407
OBJECTIVE:
To analyze the clinical phenotype and genetic variant of a child with Snijders Blok-Campeau syndrome (SBCS).
METHODS:
A child who was diagnosed with SBCS in June 2017 at Henan Children's Hospital was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and his parents were collected and the extraction of genomic DNA, which was subjected to trio-whole exome sequencing (trio-WES) and genome copy number variation (CNV) analysis. Candidate variant was verified by Sanger sequencing of his pedigree members.
RESULTS:
The main clinical manifestations of the child have included language delay, intellectual impairment and motor development delay, which were accompanied with facial dysmorphisms (broad forehead, inverted triangular face, sparse eyebrows, widely spaced eyes, narrow palpebral fissures, broad nose bridge, midface hypoplasia, thin upper lip, pointed jaw, low-set ears and posteriorly rotated ears). Trio-WES and Sanger sequencing revealed that the child has harbored a heterozygous splicing variant of the CHD3 gene, namely c.4073-2A>G, for which both of his parents were of wild-type. No pathogenic variant was identified by CNV testing.
CONCLUSION
The c.4073-2A>G splicing variant of the CHD3 gene probably underlay the SBCS in this patient.
DNA Copy Number Variations
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Heterozygote
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Pedigree
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Phenotype
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RNA Splicing
;
Mutation
5.Phenotypic and genetic analysis of a child with partial trisomy 7q.
Chaojie WANG ; Dongxiao LI ; Yaodong ZHANG ; Jinghui KONG ; Rui LI ; Chao GAO ; Qing SHANG ; Huichun ZHANG
Chinese Journal of Medical Genetics 2023;40(5):604-608
OBJECTIVE:
To define the nature and origin of a chromosomal aberration in a child with unexplained growth and development retardation, and to analyze its genotype-phenotype correlation.
METHODS:
A child who had presented at the Affiliated Children's Hospital of Zhengzhou University on July 9, 2019 was selected as the study subject. Chromosomal karyotypes of the child and her parents were determined with routine G-banding analysis. Their genomic DNA was also analyzed with single nucleotide polymorphism array (SNP array).
RESULTS:
Karyotyping analysis combined with SNP array suggested that the chromosomal karyotype of the child was 46,XX,dup(7)(q34q36.3), whilst no karyotypic abnormality was found in either of her parents. SNP array has identified a de novo 20.6 Mb duplication at 7q34q36.3 [arr[hg19] 7q34q36.3(138335828_158923941)×3] in the child.
CONCLUSION
The partial trisomy 7q carried by the child was rated as a de novo pathogenic variant. SNP array can clarify the nature and origin of chromosomal aberrations. Analysis of the correlation between genotype and phenotype can facilitate the clinical diagnosis and genetic counseling.
Female
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Humans
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Trisomy/genetics*
;
Phenotype
;
Genotype
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Karyotyping
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Chromosome Banding
6.Application of vascular axis approach in laparoscopic radical antegrade modular pancreatosplenectomy of pancreatic body and tail adenocarcinoma
Hongtao PAN ; Hao JIN ; Yong WANG ; Qing PANG ; Xiaosi HU ; Chao ZHU ; Shilei CHEN ; Huichun LIU ; Ling WANG
Chinese Journal of Hepatobiliary Surgery 2023;29(9):679-682
Objective:To explore the safety of laparoscopic antegrade modular pancreatosplenectomy (L-RAMPS) through vascular axis approach in the treatment of pancreatic body and tail adenocarcinoma.Methods:The clinical data of 12 patients with pancreatic body and tail adenocarcinoma undergoing L-RAMPS in Department of Hepatobiliary Pancreatic Surgery, Anhui No.2 Provincial People's Hospital from April 2021 to December 2022 were retrospectively analyzed, including eight males and four females, aged (65.8±11.6) years. Data regarding operative time, intraoperative blood loss, anal exhaust time, postoperative hospital stay, lymph node dissection, pathology, and postoperative complications, and survival were analyzed.Results:The procedures were successfully completed in all 12 patients. Eight patients underwent anterior L-RAMPS, four underwent posterior L-RAMPS. In one patient laparoscopic procedure was almost completed, but eventually conversed to open surgery due to vascular invasion. The operative time was (221.5±21.7) min, the intraoperative blood loss was (224.1±125.3) ml, the anal exhaust time was (3.5±1.0) d, and the postoperative hospital stay was (10.0±3.9) d. All patients underwent R 0 resection, and (15.1±3.7) lymph nodes were dissected. Positive lymph nodes were confirmed in four patients. Six patients had postoperative pancreatic fistula. The patients had been followed up for a median time of 9.5 (3.2-15.0) months, and three patients died. Conclusion:The vascular axis approach could optimize the L-RAMPS surgical approach and improve surgical safety.
7.Progress in application of hepatitis B virus core-associated antigen in differentiating natural stages of chronic HBV infection
Chinese Journal of Clinical Infectious Diseases 2022;15(1):57-60
Chronic HBV infection can generally be divided into four stages according to the natural course of disease. Clinically, the determination of different natural stages of chronic HBV infection is crucial for patients to start antiviral therapy and to avoid missing the antiviral opportunity and progressing to cirrhosis. In particular, it is a challenge for clinicians to distinguish the immune control stage from the reactive stage. As a novel marker of HBV, the quantitative detection of HBV core-associated antigen (HBcrAg) is of value for the identification of the HBV infection stages. This article reviews the research progress of HBcrAg in the identification of different stages of chronic HBV infection.
8.Associations between atopic dermatitis and systemic diseases
Litian QU ; Huichun SU ; Bo CHENG
Chinese Journal of Dermatology 2021;54(5):463-466
Atopic dermatitis (AD) is closely related to many systemic diseases, such as other allergic diseases, autoimmune diseases, infectious diseases, cardiovascular diseases and mental disorders, and the underlying mechanism is very complex. AD is considered to be a starting point of the allergy march, and affects the occurrence of various allergic diseases such as food allergies, allergic rhinitis and allergic asthma. AD is associated with the occurrence of many autoimmune diseases, decreased incidence of some malignant tumors and low serum levels of vitamin D. AD is not only a potential risk factor for multiple organ infections and osteoporosis, but also increases the risk of cardiovascular diseases, nephrotic syndrome, and skin dryness. In addition, mental disorders such as anxiety and depression are also common complications of AD. To recognize and investigate into the associations between AD and systemic diseases is of great significance for improving the prognosis and quality of life of AD patients.
9.Compound heterozygous NDUFS1 variants identified in a Chinese pedigree affected with mitochondrial respiratory chain complex I deficiency.
Chao GAO ; Baiyun CHEN ; Yang GAO ; Huichun ZHANG ; Liye SHI ; Weimeng LI ; Haibei LI ; Jiaojiao HUANG
Chinese Journal of Medical Genetics 2021;38(3):247-250
OBJECTIVE:
To explore the genetic basis for a Chinese pedigree with suspected mitochondrial functional defects through combined next-generation sequencing (NGS), copy number variation sequencing (CNV-seq), and mitochondrial DNA (mtDNA) sequencing.
METHODS:
Clinical data of the proband and his family members were collected. The patient and his parents were subjected to family-trio whole-exome sequencing (WES), CNV-seq and mtDNA variant detection. Candidate variant was verified by Sanger sequencing.
RESULTS:
Trio-WES revealed that the proband has carried compound heterozygous variants of the NDUFS1 gene, including a paternally derived c.64C>T (p.R22X) nonsense variant and a maternally derived c.845A>G (p.N282S) missense variant. Both variants may cause loss of protein function. No variant that may cause the phenotype was identified by CNV-seq and mtDNA variant analysis.
CONCLUSION
Children with suspected mitochondrial disorders may have no specific syndromes or laboratory findings. A comprehensive strategy including mtDNA testing may facilitate the diagnosis and early clinical interventions.
Child
;
China
;
DNA Copy Number Variations
;
Electron Transport
;
Humans
;
Mutation
;
NADH Dehydrogenase/genetics*
;
Pedigree
10.The predictive value of combining ultrasound elastography with serologic examination on microvascular invasion of hepatocellular carcinoma
Huichun CHEN ; Haibin TU ; Jianling LIN
Chinese Journal of Hepatobiliary Surgery 2021;27(10):744-747
Objective:To study the predictive value of combining ultrasound elestography with serological examination on incidences of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC).Methods:The clinical data of 288 patients with HCC who underwent liver resection at MengChao Hepatobiliary Hospital of Fujian Medical University from January 2018 to September 2020 were retrospectively analyzed. 104 MVI-negative and 184 MVI-positive patients who were confirmed by postoperative histopathology were divided into the MVI-negative and MVI-positive groups respectively. Serological indicators of alanine aminotransferase, aspartate aminotransferase, platelet, albumin, and alpha-fetoprotein were compared between groups. Imaging indexes including elasticity at liver tumor surrounding 1 cm area (S1), elasticity at liver tumor surrounding 2 cm area (S2), S1S2index (S1/S2×10) and longest tumor diameter were compared between groups. Multi-variate analysis was used to screen out independent risk factors in predicting MVI of hepatocellular carcinoma, and then a nomogram model was constructed.Results:Of 288 patients with HCC who met the inclusion criteria of this study, there were 225 males and 63 females, aged (56.3±9.7) years. Multivariate logistic regression analysis revealed that patients with HCC who had multiple tumors ( OR=2.47, 95% CI: 1.41-4.33, P=0.002), long tumor diameter ( OR=1.21, 95% CI: 1.08-1.36, P=0.031), AFP>400 μg/L ( OR=2.83, 95% CI: 1.54-5.22, P=0.015), a high S1S2index ( OR=1.33, 95% CI: 1.17-1.51, P=0.025) had high incidences of MVI. The nomogram model constructed from these risk factors showed the risk of MVI in HCC patients with a mean absolute deviation of compliance between the predicted value and the true value being 0.021. The receiver operating characteristic (ROC) curve showed that the area under ROC curve of the nomogram model which predicted MVI of HCC patients was 0.777 (95% CI: 0.720-0.835). Conclusions:Multiple tumors, long tumor diameter, AFP>400 μg/L and a high S1S2 index were independent risk factors for MVI in HCC patients. The nomogram model established by these factors accurately predicted the risk of MVI and provided a reference for better choice of treatment.

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