1.Improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome and its mechanism
Hong TANG ; Linxia LI ; Yu HUA ; Xiaomei JIANG ; Shiwen ZHANG ; Jinrong FU
China Pharmacy 2024;35(1):57-62
OBJECTIVE To study the improvement effects of poria acid on insulin resistance in rats with polycystic ovary syndrome (PCOS) and its mechanism. METHODS One hundred and twenty-six female rats were randomly separated into blank group, PCOS group, poria acid low-dose group (8.33 mg/kg), pachymic acid high-dose group (33.32 mg/kg), ethinylestradiol cyproterone group (positive control group, 0.34 mg/kg), recombinant rat high mobility group protein B1 protein (rHMGB1) group (8 μg/kg), and poria acid high dose+rHMGB1 group (33.32 mg/kg poria acid+8 μg/kg rHMGB1), with 18 rats in each group. Except for the blank group, the rats in all other groups were given Letrozole suspension intragastrically to construct the PCOS model. After successful modeling, administration was performed once a day for 4 weeks. After medication, the fasting blood glucose and fasting insulin levels, and insulin resistance index (HOMA-IR) were measured in rats; the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone (T) in rat serum, and the levels of interleukin-1β (IL-1β) and tumor necrosis factor- α (TNF- α) in ovarian tissue were detected; ovarian coefficients of rats were calculated; the pathological changes of ovarian tissue were observed; the expressions of HMGB1, receptor for advanced glycosylation elaine_ tanghong@sina.com end product (RAGE) and phosphorylated nuclear factor κB p65 (p-NF-κB p65) proteins were determined in ovarian tissue of rats. RESULTS Compared with the blank group, the pathological injury of ovarian tissue of rats in the PCOS group was serious, the levels of fasting blood glucose and fasting insulin, HOMA-IR and ovarian coefficient were increased, the levels of serum LH and T were increased, while the levels of FSH were decreased; the levels of IL-1β and TNF-α, the expressions of HMGB1, RAGE and p-NF-κB p65 protein in ovarian tissue were increased, with statistical significance (P<0.05). Compared with the PCOS group, pathological damage of ovarian tissue was reduced in poria acid low-dose and high-dose groups and ethinylestradiol cyproterone group, and fasting blood glucose, fasting insulin levels, HOMA-IR and ovarian coefficient were decreased; serum LH and T levels were decreased, while FSH levels were increased; the levels of IL-1β and TNF-α and the expressions of HMGB1, RAGE and p-NF-κB p65 protein in ovarian tissue were decreased, with statistical significance (P<0.05). The trend of corresponding indexes in rHMGB1 group was opposite to the above (P<0.05). Compared with poria acid high-dose group, the changes of the above indexes were reversed significantly in poria acid high-dose+rHMGB1 group (P<0.05). CONCLUSIONS Poria acid may improve insulin resistance and inhibit inflammatory reaction in PCOS rats by inhibiting HMGB1/ RAGE pathway.
2.Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review
Pin YANG ; Cizheng ZENG ; Xuwei TAO ; Shiwen RONG ; Yu LONG ; Lingkong ZENG
Chinese Journal of Pediatrics 2024;62(1):43-48
Objective:To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation.Methods:This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized.Results:The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations.Conclusions:Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.
3.Exploration of Basement Membrane-related Markersand Prediction of Therapeutic Drugs in Idiopathic Pulmonary Fibrosis
Yifeng XU ; Shiwen KE ; Hang XIAO ; Wenqiang ZHANG ; Shaobin XIONG ; Xiaogang XU ; Yu WANG ; Liangji LIU
Herald of Medicine 2024;43(8):1338-1346
Objective To explore basement membrane markers and potential drugs for treatment in idiopathic pulmona-ry fibrosis(IPF).Methods IPF-related datasets were downloaded from the Gene Expression Omnibus(GEO)database,processed to construct basement membrane gene expression matrices associated with IPF,and screened for differential basement membrane genes(DEBMs);DEBMs were enriched for function and pathways,and machine learning algorithms were used to ob-tain candidate signature genes,receiver operating characteristic(ROC)curves were used to identify signature genes and con-struct a nomogram.We performed ssGSEA analysis to explore the correlation between signature genes and immune cells and their functions and predicted the corresponding miRNAs and therapeutic drugs by signature genes.Results A total of 56 DEBMs were extracted;enrichment analysis showed that DEBMs were mainly enriched in"extracellular matrix tissue","extracellular structural tissue",etc.,and were closely related to"ECM-receptor interaction"and"local adhesion spot"pathways.The ma-chine learning has identified six candidate signature genes(TIMP3,P3H2,ITGA7,ITGA4,ADAMTS2,COL8A2),all of which meet the requirements of the signature genes by the ROC curve test,and the nomogram diagnostic value was outstanding(AUC=0.991 523);B cells and Macrophages in IPF were significantly different from the normal group.Finally,miRNAs were predicted to be dominated by miR-4305,miR-3684,progesterone,and tert-butyl hydroperoxide as therapeutic agents with strong relevance to IPF.Conclusion Signature genes and predictive miRNAs may serve as novel markers for IPF diagnosis,and pre-dictive drugs may be a potential source of drugs for treating IPF.
4.Role of oxidative stress and immune infiltration in idiopathic pulmonary fibrosis and study of Chinese medicine for prevention and treatment
Yifeng XU ; Shiwen KE ; Keke LI ; Zhaoqi YAN ; Yueqi XU ; Xiaogang XU ; Yu WANG ; Liangji LIU
Chinese Journal of Immunology 2024;40(10):2108-2115,中插5
Objective:To explore the role and relationship between oxidative stress and immune infiltration in idiopathic pul-monary fibrosis(IPF),and to predict the relevant therapeutic herbal medicines and active ingredients.Methods:GSE10667 gene expression profiles were downloaded from GEO database to obtain differential expression genes,differential expression of oxidative stress genes(DEOSGs)were identified in combination with oxidative stress genes.GSEA was used to evaluate the pathways and biologi-cal processes in IPF,and GO,KEGG and PPI network analysis were performed on DEOSGs.Candidate central genes were derived from PPI results and CytoHubba,and GSE110147 was validated as an independent group to identify central genes;in addition,the immune microenvironment of samples was evaluated using CIBERSORTF,and correlation between central gene levels and relative proportion of immune cells was explored;finally,therapeutic herbal medicines and components were predicted by central genes,and mole-cular docking verification was carried out.Results:A total of 51 DEOSGs,four central genes(ICAM-1,APOE,MMP-1,TGF-β2)were obtained;DEOSGs were mainly related to oxidative stress,immune response,etc;four central gene levels were closely correlated with 8 relative proportions of immune cells;therapeutic herbal medicines included 4 flavors such as Huangqi and Chuanxiong,and the active ingredients included 8 kinds of β-carotene,etc,the molecular docking results were stable.Conclusion:Oxidative stress and immune firing are exist in IPF,and oxidative stress may be recognized by immune cells or directly activate immune cells.
6.Epidemiological characteristics of facial trauma in preschool children in Fuyang City of Anhui Province
YU Xiaofeng, LI Xinyi , MA Jie , FANG Jianqiang, SUN Shiwen, CHENG Qiyuan
Chinese Journal of School Health 2022;43(3):452-454
Objective:
To investigate the current situation and related factors of facial trauma in school age children in urban areas of Fuyang, and to provide basis for child facial trauma prevention.
Methods:
By cluster stratified random sampling method, a questionnaire survey was conducted among parents of school age children aged 3-6 in four kindergartens in Fuyang City. A total of 1 062 valid questionnaires were included.
Results:
A total of 146 (13.7%) children with facial trauma were included. The ratio of boys to girls was 1.84∶1.In primary and secondary classes in kindergarten, the reporting rate of boys (24.5%,16.4%) was higher than that of girls (13.4%, 9.0%), and the difference was statistically significant ( χ 2=6.66, 4.25, P <0.05).The incidence of facial trauma was highest (19.4%) in junior kindergarten class children, which decreased with age. Falls injury(61.6%) was the leading cause of facial trauma. Most of facial trauma occurred in family (55.5%) and kindergarten (26.0%). Forehead (26.0%) and mandible (21.2%) were the main injured body sites. Skin laceration (81.5%) was the main type of injury. Facial trauma mostly occurred at 11:00-13:00(19.9%) and 17:00-19:00(27.4%), during June to August (39.7%). The results of univariate analysis showed that the facial trauma of preschool children was associated with gender, class, parentrated child temperament, parental education and family type( χ 2=14.51,18.84,39.66,6.56,12.31, P <0.05).
Conclusion
Facial trauma in preschool children in Fuyang is common, which varies in gender, class, temperament and family type.
7.Development and evaluation of the detection method of rapid RT-PCR assays for severe fever with thrombocytopenia syndrome virus, dengue virus and hantaan virus
Tingting HU ; Yu ZHU ; Aqian LI ; Lina SUN ; Xiaoxia HUANG ; Wei WU ; Chuan LI ; Qin WANG ; Jiandong LI ; Dexin LI ; Shiwen WANG ; Yan LIU ; Mifang LIANG ; Xiaofang WANG
Chinese Journal of Experimental and Clinical Virology 2022;36(2):230-235
Objective:To establish a quick on-site emergency detection method for severe fever with thrombocytopenia syndrome virus (SFTSV), dengue virus (DENV), and hantaan virus (HTNV).Methods:This research was based on the traditional TaqMan fluorescent probe technology, using the domestic rapid one-step quantitative RT-PCR kit, combined with the Magnetic induction cycler (Mic) qPCR instrument. The detection limit, specificity and repeatability of this method were evaluated by simulated samples, other virus infected samples and normal human blood samples.Results:Compared with the traditional RT-PCR assay, the required time of this method was greatly shortened, and the detection can be completed within 35 minutes. The limit of quantitation for SFTSV, DENV and HTNV are less than 100copies/PCR. No nonspecific amplification was found in the simulated negative samples and other virus infected samples. All the simulated positive sample for verification could be detected, and coefficient of variation Ct value of each group was less than 4%. Conclusions:The rapid fluorescence quantitative RT-PCR assays have certain application prospects for on-site emergency detection, and provide important technical supports and new directions for the prevention and control of common hemorrhagic fever viruses.
8.Perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery for pelvic fractures: a prospective randomized control trial
Jinhui WANG ; Yufeng GE ; Xianfeng GUO ; Li TAO ; Xiaohua LIU ; Qiang LI ; Yuzhang WANG ; Minghui YANG ; Shiwen ZHU ; Zhenzhong WANG ; Lin JIN ; Zhiyong HOU ; Jian JIA ; Liancheng WANG ; Bin YU ; Xinbao WU
Chinese Journal of Orthopaedic Trauma 2021;23(10):850-855
Objective:To evaluate the efficacy and safety of perioperative rehabilitation approaches based on the concept of Enhanced Recovery After Surgery (ERAS) for pelvic fractures.Methods:A prospective randomized control trial was conducted to include 114 emergency patients who had been admitted to Department of Orthopaedic Trauma, Beijing Jishuitan Hospital for surgical treatment of pelvic fractures from June 2019 to December 2020. Of them, 57 were assigned into an intervention group according to a random digits table. They were 42 males and 15 females, aged from 18 to 77 years and subjected to management of pelvic fractures with tentative perioperative ERAS approaches which were adjusted at different stages. The other random 57 patients were assigned into a control group. They were 40 males and 17 females, aged from 17 to 70 years and subjected to management of pelvic fractures with conventional rehabilitation approaches which included postoperative in-hospital consultation and guidance by rehabilitation physicians. The 2 groups were compared in terms of Majeed pelvis scores and Barthel indexes at postoperative 2, 6, 12 and 24 weeks, and visual analogue scale (VAS) pain scores and SF36 scores at postoperative 12 and 24 weeks.Results:A total of 105 patients (55 in the intervention group and 50 in the control group) were completely followed up for 151 to 254 d (mean, 177 d). The 2 groups were comparable due to no significant difference between them in the preoperative general data ( P>0.05). The Majeed scores (44±13, 67±16, 86±14 and 98±7) and Barthel indexes (57±13, 79±16, 95±8 and 100±2) at postoperative 2, 6, 12 and 24 weeks in the intervention group were significantly higher than those in the control group [(35±16, 51±16, 73±14 and 91±12) and (45±19, 67±18, 86±12 and 98±4)] (all P<0.05). At postoperative 12 and 24 weeks, the SF-36 scores (129±15 and 141±6) in the intervention group were significantly higher than those in the control group (114±15 and 131±12) ( P<0.05). There was no significant difference in the pain degree between the 2 groups ( P>0.05). Conclusion:In management of pelvic fractures, compared with conventional perioperative rehabilitation approaches, the perioperative ERAS rehabilitation approaches may improve early functional outcomes and thus help the patients restore their activities of daily living earlier.
9.Hepatotoxicity of Main Components of Polygonum multiflorum and Its Effects on Drug Metabolism Enzyme
Xiaoyuan ZHENG ; Zhijie YU ; Xuan WANG ; Shiwen ZHOU
China Pharmacy 2021;32(21):2619-2623
OBJECTIVE:To study the hepatotoxicity of main components of Polygonum multiflorum ,and investigate its toxic mechanism based on metabolic enzymes. METHODS :ADMETlab 2.0 platform was used to forecast the toxic or carcinogenic effects of emodin ,physcion,rhein,stilbene glycoside and gallic acid on liver ,skin and heart. The effects of those components on cytochrome P 450 enzyme system (CYP1A2,CYP2C9,CYP2C19,CYP2D6,CYP3A4)were evaluated. The effects of different concentrations of emodin ,rhein,stilbene glycoside and gallic acid (10,20,40,80 μmol/L)on the survival rate of normal hepatocyte L 02 were detected. The effects of major components of P. multiflorum on the activity of UGT 1A1 enzyme were studied by in vitro reaction system ,using bilirubin as substrate. RESULTS :Main components of P. multiflorum ,ie. emodin ,physcion, rhein and gallic acid ,showed strong toxic effects on the liver ,while stilbene glycosides possessed weak toxic effects on the liver. Emodin and physcion had strong inhibitory effects on CYP 1A2 and medium inhibitory effects on CYP 2C9,CYP2D6 and CYP3A4;rhein showed medium inhibitory effects on CYP 1A2 and CYP 2C9,while stilbene glycoside and gallic acid possessed weak inhibitory effects on the above enzymes. Emodin (40,80 μmol/L)and gallic acid (40,80 μmol/L)could significantly reduce the survival rate of L 02 cells(P<0.01). The inhibition rate of 5,10,20,40,80 μmol/L emodin and gallic acid(except for 5 μmol/L emodin)on UGT 1A1 enzyme increased significantly (P<0.01),and the inhibition effect of emodin on UGT 1A1 enzyme was reversible competitive inhibition. CONCLUSIONS :The main components of P. multiflorum ,ie. emodin ,rhein and physcion , are hepatotoxic ;the mechanism of it may be associated with inhibiting the activity of CYP 1A2 and CYP 2C9 and competitively blocking rate-limiting enzyme UGT 1A1 in the process of bilirubin metabolism.
10.Analysis of the pulmonary function characteristics and associated factors in silicosis patients with progressive massive fibrosis
Shiwen YU ; An LI ; Yuguo SONG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2021;39(11):831-835
Objective:To investigate the characteristics of and associated risk factors for pulmonary dysfunction in silicosis patients with progressive massive fibrosis (PMF) .Methods:In-patients with PMF treated in the Department of Occupational Medicine and Toxicology in Beijing Chao-Yang Hospital, Capital Medical University from June 2014 to October 2020 were enrolled in this study. Based on their pulmonary ventilation function, the patients were divided into normal ventilation group, obstructive ventilation dysfunction group, restrictive ventilation dysfunction group, and mixed ventilation dysfunction group. The location and area of the large opacity and the grade of emphysema were evaluated by high-resolution CT (HRCT) of the chest. Based on the location, the large opacity was classified into central type, peripheral type, and mixed type.Results:A total of 115 silicosis patients with PMF were enrolled, with 85 (73.91%) having different types of pulmonary dysfunction, including 36 cases (31.30%) in the obstructive ventilation dysfunction group, 9 cases (7.83%) in the restrictive ventilation dysfunction group and 40 cases (34.78%) in the mixed ventilation dysfunction group. As for the location of the large opacity, 41 cases (35.65%) were central type, 52 cases (45.22%) were peripheral type, and 22 cases (19.13%) were mixed type. Logistic regression analysis showed that the central large opacity and grade 3-4 emphysema were risk factors for obstructive ventilation dysfunction ( OR=52.179, 5.500, P<0.05) , class C large opacity was the risk factor for restrictive ventilation dysfunction ( OR=33.146, P<0.05) , class B, class C large opacity and central large opacity were the risk factors for mixed ventilation dysfunction ( OR=6.414, 11.561, 19.600, P<0.05) . Conclusion:In silicosis patients with PMF, the incidence rate of pulmonary ventilation dysfunction is higher, mainly obstructive and mixed ventilation dysfunction. The area and location of large opacity are associated with the incidence and types of pulmonary ventilation dysfunction.


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