1.Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
Jinjin WANG ; Wenfei CUI ; Xuewei DOU ; Binglei YIN ; Yuqi NIU ; Ling NIU ; Guoli YAN
Journal of Southern Medical University 2024;44(7):1243-1255
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.
2.A multicenter study of neonatal stroke in Shenzhen,China
Li-Xiu SHI ; Jin-Xing FENG ; Yan-Fang WEI ; Xin-Ru LU ; Yu-Xi ZHANG ; Lin-Ying YANG ; Sheng-Nan HE ; Pei-Juan CHEN ; Jing HAN ; Cheng CHEN ; Hui-Ying TU ; Zhang-Bin YU ; Jin-Jie HUANG ; Shu-Juan ZENG ; Wan-Ling CHEN ; Ying LIU ; Yan-Ping GUO ; Jiao-Yu MAO ; Xiao-Dong LI ; Qian-Shen ZHANG ; Zhi-Li XIE ; Mei-Ying HUANG ; Kun-Shan YAN ; Er-Ya YING ; Jun CHEN ; Yan-Rong WANG ; Ya-Ping LIU ; Bo SONG ; Hua-Yan LIU ; Xiao-Dong XIAO ; Hong TANG ; Yu-Na WANG ; Yin-Sha CAI ; Qi LONG ; Han-Qiang XU ; Hui-Zhan WANG ; Qian SUN ; Fang HAN ; Rui-Biao ZHANG ; Chuan-Zhong YANG ; Lei DOU ; Hui-Ju SHI ; Rui WANG ; Ping JIANG ; Shenzhen Neonatal Data Network
Chinese Journal of Contemporary Pediatrics 2024;26(5):450-455
Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75%(27/36);boys accounted for 64%(23/36).Among the 36 neonates,31(86%)had disease onset within 3 days after birth,and 19(53%)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61%)had left cerebral infarction and 13(36%)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75%)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72%)and seizures in 10 neonates(34%).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33%,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44%(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.
3.Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway
Jinjin WANG ; Wenfei CUI ; Xuewei DOU ; Binglei YIN ; Yuqi NIU ; Ling NIU ; Guoli YAN
Journal of Southern Medical University 2024;44(7):1243-1255
Objective To explore the therapeutic mechanism of Euonymus alatus for diabetic kidney disease(DKD).Methods TCMSP,PubChem and Swiss Target Prediction databases were used to obtain the active ingredients in Euonymus alatus and their targets.GEO database and R language were used to analyze the differentially expressed genes in DKD.The therapeutic targets of DKD were obtained using GeneCards,DisGeNet,OMIM and TTD databases.The protein-protein interaction network and the"drug-component-target-disease"network were constructed for analyzing the topological properties of the core targets,which were functionally annotated using GO and KEGG pathway enrichment analyses.Molecular docking was performed for the core targets and the main pharmacologically active components,and the results were verified in db/db mice.Results Analysis of GSE96804,GSE30528 and GSE30529 datasets(including 60 DKD patients and 45 normal samples)identified 111 differentially expressed genes in DKD.Network pharmacology analysis obtained 161 intersecting genes between the target genes of Euonymus alatus and DKD,including the key core target genes SRC,EGFR,and AKT1.The core active ingredients of Euonymus alatus were quercetin,kaempferol,diosmetin,and naringenin,which were associated with responses to xenobiotic stimulionus and protein phosphorylation and regulated EGFR tyrosine kinase inhibitor resistance pathways.Molecular docking suggested good binding activities of the core active components of Euonymus alatus with the core targets.In db/db mouse models of DKD,treatment with Euonymus alatus obviously ameliorated kidney pathologies,significantly inhibited renal expressions of SRC,EGFR and AKT1,and delayed the progression of DKD.Conclusion Euonymus alatus contains multiple active ingredients such as quercetin,kakaferol,diosmetin,naringenin,which regulate the expressions of SRC,EGFR,and AKT1 to affect the EGFR tyrosine kinase inhibitor resistance signaling pathway to delay the progression of DKD.
4.Probing the Impact of Whole Intestinal Microbiota Transplantation from Alzheimer's Disease Model Mice on the Ileal Microenvironment Based on the “Interior-Exterior Relationship Exists Between Heart and Small Intestine”
Wei XIONG ; Ling HU ; Qing XU ; Xi LI ; Xian DING ; Chong-yang DOU ; Fang-fang CHENG ; Zhi-yong YAN
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(1):63-70
ObjectiveTo investigate whether the whole intestinal microbiota transplantation in Alzheimer's disease (AD) model mice has more significant effects on ileum intestinal microenvironment in normal mice under the guidance of the theory of traditional Chinese medicine that "interior-exterior relationship exists between the heart and small intestine". MethodsThe whole intestinal microbiota of fourteen 6-month-old specific pathogen free male APP/PS1 double-transgenic AD model mice was transplanted into the gut of six normal C57BL/6J mice of the same age and background treated with mixed antibiotics for 14 days. Then, after 14 days of normal rearing, the mice were sacrificed. Next, the pathological changes in the ileum and colon were observed, and the composition and diversity of the ileal and colonic microbiota was analyzed by sequencing. ResultsAfter the whole intestinal microbiota of AD mice was transplanted into normal mice, pathological analysis showed that only the ileum tissue had mucosal damage and crypt gland epithelial cell degeneration, necrosis, and shedding. Moreover, the microbiota analysis found that only the number of genera (P<0.01), Chao1 index (P<0.01) and Simpson index of ileal microbiota in normal mice decreased (P<0.01), and the composition of intestinal microbiota was quite similar to that of AD model mice. ConclusionUnder the effect of whole gut microbiota transplantation in AD mice, the diversity and composition of ileal microbiota change more than that of colonic microbiota in normal mice, and at the same time, it results in pathological damage to the ileal mucosa, indicating that the ileal microenvironment may be more closely related to the occurrence and development of AD, which is highly consistent with the traditional Chinese medicine theory of "interior-exterior relationship between heart and small intestine".
5.Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation
Jia-Yi DOU ; Yu-Chen JIANG ; Zhong-He HU ; Kun-Chen YAO ; Ming-Hui YUAN ; Xiao-Xue BAO ; Mei-Jie ZHOU ; Yue LIU ; Zhao-Xu LI ; Li-Hua LIAN ; Ji-Xing NAN ; Yan-Ling WU
Biomolecules & Therapeutics 2022;30(3):246-256
The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.
6.Intra-abdominal aortic balloon occlusion in the management of placenta percreta.
Weiran ZHENG ; Ruochong DOU ; Jie YAN ; Xinrui YANG ; Xianlan ZHAO ; Dunjin CHEN ; Yuyan MA ; Weishe ZHANG ; Yiling DING ; Ling FAN ; Huixia YANG
Chinese Medical Journal 2022;135(4):441-446
BACKGROUND:
Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients.
METHODS:
We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed.
RESULTS:
One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups.
CONCLUSIONS
IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.
Aorta
;
Balloon Occlusion/methods*
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Blood Loss, Surgical
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Female
;
Humans
;
Hysterectomy
;
Infant, Newborn
;
Placenta Accreta/surgery*
;
Placenta Previa/surgery*
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Postpartum Hemorrhage
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Pregnancy
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Retrospective Studies
7.Analysis of the etiology and clinical characteristics of infants with moderate-severe visual impairment
Ning WEI ; Guang-Qiang WU ; Yan-Lu HE ; Jia-Chen WU ; Qing-Yun GE ; Xin-Xuan DOU ; Qin WANG ; Mei-Ling TONG
International Eye Science 2022;22(9):1583-1586
AIM: To explore the etiology classification and clinical characteristics of infants with moderate-severe visual impairment aged 0-2 years old, and preliminarily formulate a set of process for grass-roots health-care institutions to carry out the screening and management of children visual impairment.METHODS: There were 245 cases of children aged 0-2 years with moderate-severe visual impairment who were admitted to the Children Eye Care Specialist Clinic in Nanjing Maternal and Child Health Hospital from January 2009 to December 2020 were retrospectively analyzed. A complete profile of visual development was established, including age, sex, medical history, vision, eye position and movement, anterior segment examination, fundus examination, refractive examination under cycloplegia with 1% atropine ophthalmic gel, if necessary, some special eye examinations such as fundus photography, eye A/B ultrasound and visual electrophysiology were received.RESULTS: The average visit age of 245 cases of infants was 1.82±0.79 years, including refraction error of 128 cases(52.2%), among them, 100 cases(40.8%)were high refraction error; 79 cases(32.2%)were eye diseases, most of which were congenital cataract(33 cases); and 38 cases(15.5%)were cerebral visual impairment(CVI)(15.5%).CONCLUSION: It is necessary to proceed classified managements according to the etiology and clinical characteristics of infant visual impairment to find early and diagnose and treat multidisciplinary,including drawing up screening plans for remediable eye diseases, carrying out necessary refractive correction and training children to use residual visual function.
8. Role of pyroptosis in severe COVID-19
Dou-Dou HUANG ; Zhi-Hui LI ; Yu-Xuan DONG ; Yu-Yan LING ; Ling GU ; Mei-Juan CHEN
Chinese Pharmacological Bulletin 2022;38(9):1303-1308
Corona virus disease 2019 (COVID-19) is an infec¬tious disease endangering the respirator)' traet and multiple or¬gans of the whole body caused by severe aeute respirator)' syn¬drome coronavirus 2 ( SARS-CoV-2).More than 200 million people in the world have been infected with the disease, which is an unprecedented global plague.Most patients with C0VID-19 only show mild symptoms with a good prognosis, but about 20% of them may develop into severe cases and eause serious compli-cations, including acute respirator)' distress syndrome ( ARDS) , systemic inflammatory response syndrome (SIRS) , cytokine re¬lease syndrome (CRS) , etc.Pyroptosis is a kind of programmed cell death characterized by significant inflammatory response.It is often mediated by inflammatory caspase and the gasdermin family of membrane perforating proteins is the final effector mol¬ecules, resulting in cell membrane swelling and rupture to death, accompanied by the release of a large number of pro-in¬flammatory cytokines (such as IL-lp and IL-18, etc).Pyropto- sis affects the occurrence, progression and treatment of many diseases due to its inflammatory and morphological characteris¬tics, and also plays an important role in severe COVID-19.Therefore, drugs that target key molecules in the pyroapoptotic pathway could he a promising breakthrough for treating severe COVID-19.This article reviews the role of pyroptosis in severe COVID-19 complications ARDS and CHS.
9.Analysis on quality value transfer of substance benchmarks of Qingwei San.
Jia-Yi HUANG ; Qi ZHANG ; Yan-Ling YANG ; Hai-Ju YANG ; Min-Hang DOU ; Hua-Hua LI ; Shou-Ying DU ; Jie BAI
China Journal of Chinese Materia Medica 2021;46(4):792-800
By preparing 10 batches of substance benchmarks freeze-drying powder( lyophilized powder),the methodology of the characteristic spectrum and the content of index component for substance benchmarks of Qingwei San was established. The characteristic peaks and the similarity range of the characteristic spectrum,the contents and the transfer rate range of isoferulic acid,palmatine and paeonol,and the paste-forming rate range were determined to define key quality attributes of substance benchmarks of Qingwei San. In the10 batches of substance benchmarks of Qingwei San,the similarity of characteristic spectrum was higher than 0. 90. In further comparison of the characteristic peak information,a total of 16 characteristic peaks were identified,including 5 characteristic peaks from Cimicifugae Rhizoma,5 characteristic peaks from Coptidis Rhizoma,2 characteristic peaks from Angelicae Sinensis Radix and 4 characteristic peaks from Moutan Cortex. The content of isoferulic acid was 0. 10%-0. 18%,with the average transfer rate of 49. 82%±4. 02%. The content of palmatine was 0. 17%-0. 31%,with the average transfer rate of 15. 84% ±2. 39%. The content of paeonol was 0. 41%-0. 75%,with the average transfer rate of 23. 41%±3. 23%. The paste-forming rate of the 10 batches of substance benchmarks were controlled at 27%-33%,with the transfer rate between the theoretical paste-forming rate and the actual paste-forming rate was 86. 59%±3. 39%. In this study,the quality value transfer of substance benchmarks of Qingwei San was analyzed by the combination of characteristic spectrum,the content of index component and the paste-forming rate. A scientific and stable evaluation method was preliminarily established,so as to provide the basis for subsequent development and quality control of relevant preparations of Qingwei San.
Benchmarking
;
Chromatography, High Pressure Liquid
;
Drugs, Chinese Herbal
;
Powders
;
Quality Control
;
Rhizome
10.Advance in Risk Assessment Tools for Pressure Injury of Patients with Spinal Cord Injury
Ya-bin ZHANG ; Ling GOU ; Chun-yan HAN ; Ju-hong PEI ; Cun ZHAO ; Xin-man DOU
Chinese Journal of Rehabilitation Theory and Practice 2020;26(10):1142-1146
Spinal cord injury (SCI) is a common traumatic disease. Patients with limited mobility are prone to pressure injuries, which seriously affect the patient's rehabilitation process. The use of risk assessment scale can effectively predict the occurrence of pressure injuries. This article reviewed the pathogenesis, risk factors, and use of different risk assessment tools for patients with spinal cord injury, compared the content, assessment methods, applicable population, reliability and validity of each risk assessment scale, summarized the advantages and disadvantages of different assessment scales, and provided reference to choose the best risk assessment tool.

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