1.Effects of low and high shear stress on tight junctions of endothelial cells
Qiang SHU ; Xin JIN ; Guangli LING
Chinese Journal of Pathophysiology 1999;0(09):-
AIM: To investigate the effect of high and low shear stress on endothelial permeability and tight junctions(TJs). METHODS: Rabbit abdominal aortas in normal and high fat diet groups were stenosed to 60.7%?7.0% of original cross areas, they were sacrificed after 7 days, and the arteries were stained with Evans blue and Sudan Ⅳ. TJs were investigated with freeze fracture. RESULTS: The non-stenosis aortas were negative, there are 1 mm-wide constant and circular positive areas proximal and distal to the stenosis and scattered, dotted and patched positive areas within 8 mm distal to stenosis. Freeze fracture reveals that in the hyperpermeable regions, the percentages of zonular type of TJs and the numbers of strands of TJs of zonular and macular types in the distal regions are significantly lower than those in the proximal regions (P
2.Reduction of intimal thickening by inhibition of early rat medial smooth muscle cell proliferation induced by arterial injury
Qiang SHU ; Enjin SHI ; Jian JIANG ; Guangli LING
Chinese Journal of Pathophysiology 1989;0(05):-
AIM: To investigate the relationship between medial smooth muscle cell proliferation and intimal thickening.METHODS: Angiotensin converting enzyme inhibitor (temocapril-HCl, 10 mg?kg -1 ?d -1 ) was administered in various periods after rat arterial injury by balloon catheters. The labeling BrdU indexes of smooth muscle cell and intimal areas were observed. RESULTS: Positive medial smooth muscle cells for BrdU occurred at 24 hours after injury. The labeling indexes for BrdU showed biphasic change, the period of the first peak appeared within day 1-3, the peak value was 5 3% at 2 days. The period of the second peak appeared within day 3-7, the peak was 2 7% at 5 days. Administration of temocapril in the first proliferation phase significantly suppressed the labeling BrdU index(0 05?0 02)% vs (4 50?0 27)%, P0 05 ). CONCLUSION: The first proliferative phase of arterial medial smooth muscle cell after balloon injury is necessary to the intimal formation.
3.Clinical diagnosis, treatment, and prognosis of pulmonary artery sling in 38 children
Gan ZHOU ; Guangli ZHANG ; Hui ZHANG ; Xin ZOU ; Ming CHEN ; Qingqing MENG ; Ling HE ; Zhengxiu LUO
Journal of Clinical Pediatrics 2016;34(6):461-464
Objective To explore the clinical characteristics and prognosis of congenital pulmonary artery sling (PAS) in children. MethodsThe clinical data of 38 children diagnosed with PAS during June 2009 and February 2015 were retrospectively analyzed. ResultsIn 38 PAS children, 35 cases (89.47%) were hospitalized for varying degrees of respiratory manifestations with recurrent cough (89.47%) and wheezing (84.21%) being the most common. The remaining 3 cases were found abnormal in routine preoperative examination and the diagnosis was confirmed after further examination. All 38 children were performed computer tomography angiography (CTA). Thirty-seven cases were diagnosed of PAS and diagnostic rate was 97.37%. One case was suspected of pulmonary dysplasia and diagnosed of PAS after operation. Twenty-six children received surgical treatment, of whom 25 children had pulmonary artery reconstruction (LPA). Seven children died during/after operation and 18 survived. The remaining 12 children received non-surgical treatment, of whom 9 died and 3 survived.ConclusionCardiac uhrasonography may reveal PAS in the early stage, while CTA is the best method for conifrmed diagnosis. LPA reconstruction is an important means of relieving left pulmonary artery oppression.
4.The effects of emodin on lipopolysaccharide induced pyroptosis of human dental pulp fibroblasts by regula-ting HMGB1/TLR4 signaling pathway
Guangli FU ; Lijuan SONG ; Ling TU
Journal of Practical Stomatology 2024;40(5):631-637
Objective:To investigate the effects of emodin on lipopolysaccharide(LPS)induced pyroptosis of human dental pulp fibro-blasts(HDPFs)by regulating the high mobility group protein B1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods:HDPFs were in vitro cultured and grouped into control(normal culture),LPS with low,medium and high dose emodin groups,pcDNA(transfected with pcDNA3.1)and pcDNA-HMGB1 groups(transfected with pcDNA3.1 HMMGB1).qRT-PCR was applied to detect the expression level of HMGB1 mRNA in cells,MTT assay,plate cloning assay and flow cytometry were applied to detect cell prolifera-tion and pyrotosis,respectively.ELISA was applied to detect levels of IL-18,IL-1β and TNF-α in cell supernatant.Western blot was applied to detect the expression of pyroptosis protein Nod-like receptor protein 3(NLRP3),cleaved caspase-1,GSDMD,HMGB1 and TLR4 proteins in the cells.Results:Compared with the control group,the HMGB1 mRNA level,pyrotosis rate,IL-18,IL-1β,TNF-α levels,NLRP3,cleaved Caspase-1,GSDMD,HMGB1,TLR4 protein levels in the LPS group obviously increased,the A490 value and colony formation obviously decreased(P<0.05).Compared with the LPS group,the above indicators in the low,medium,and high dose emodin groups decreased,the A490 value and colony formation increased,the high-dose emodin group showed more obvious changes(P<0.05);overexpression of HMGB1 attenuated the inhibitory effects of emodin on LPS-induced pyroptosis and inflammation of HDPFs,and promoted cell proliferation(P<0.05).Conclusion:Emodin inhibit the activation of NLRP3 inflammasome by inhibiting the HMGB1/TLR4 pathway,thereby reduces LPS induced pyroptosis of HDPFs.
5.Research progress in chemical composition and pharmacological action of Astragali Radix and Atractylodis Macrocephalae Rhizoma
Huiqiang LIU ; Guangli YAN ; Ling KONG ; Yu GUAN ; Xijun WANG
International Journal of Traditional Chinese Medicine 2023;45(9):1192-1196
After the compatibility of Astragali Radix and Atractylodis Macrocephalae Rhizoma, most of the effective components of Astragali Radix increase, and the bioavailability is improved. Compared with the application of the two drugs alone, it can enhance the effects of immune regulation, anti-tumor, diuresis, lung protection, regulation of flora, and intestinal protection. However, the optimal compatibility ratio of Astragali Radix- Atractylodis Macrocephalae Rhizoma pair to exert various pharmacological effects still needs to be clarified. The drug pair and related preparations are mostly used in the treatment of nephropathy, but its mechanism of action needs to be further elucidated.
6. General considerations of model-based meta-analysis
Lujin LI ; Junjie DING ; Dongyang LIU ; Xipei WANG ; Chenhui DENG ; Shangmin JI ; Wenjun CHEN ; Guangli MA ; Kun WANG ; Yucheng SHENG ; Ling XU ; Qi PEI ; Yuancheng CHEN ; Rui CHEN ; Jun SHI ; Gailing LI ; Yaning WANG ; Yuzhu WANG ; Haitang XIE ; Tianyan ZHOU ; Yi FANG ; Jing ZHANG ; Zheng JIAO ; Bei HU ; Qingshan ZHENG
Chinese Journal of Clinical Pharmacology and Therapeutics 2020;25(11):1250-1267
With the increasing cost of drug development and clinical trials, it is of great value to make full use of all kinds of data to improve the efficiency of drug development and to provide valid information for medication guidelines. Model-based meta-analysis (MBMA) combines mathematical models with meta-analysis to integrate information from multiple sources (preclinical and clinical data, etc.) and multiple dimensions (targets/mechanisms, pharmacokinetics/pharmacodynamics, diseases/indications, populations, regimens, biomarkers/efficacy/safety, etc.), which not only provides decision-making for all key points of drug development, but also provides effective information for rational drug use and cost-effectiveness analysis. The classical meta-analysis requires high homogeneity of the data, while MBMA can combine and analyze the heterogeneous data of different doses, different time courses, and different populations through modeling, so as to quantify the dose-effect relationship, time-effect relationship, and the relevant impact factors, and thus the efficacy or safety features at the level of dose, time and covariable that have not been involved in previous studies. Although the modeling and simulation methods of MBMA are similar to population pharmacokinetics/pharmacodynamics (Pop PK/PD), compared with Pop PK/PD, the advantage of MBMA is that it can make full use of literature data, which not only improves the strength of evidence, but also can answer the questions that have not been proved or can not be answered by a single study. At present, MBMA has become one of the important methods in the strategy of model-informed drug development (MIDD). This paper will focus on the application value, data analysis plan, data acquisition and processing, data analysis and reporting of MBMA, in order to provide reference for the application of MBMA in drug development and clinical practice.
7.Traditional Chinese Medicine Treats Acute Lung Injury by Modulating NLRP3 Inflammasome: A Review
Jiaojiao MENG ; Lei LIU ; Yuqi FU ; Hui SUN ; Guangli YAN ; Ling KONG ; Ying HAN ; Xijun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):292-301
Acute lung injury (ALI) is one of the most common and critical diseases in clinical practice, with extremely high morbidity and mortality, seriously threatening human life and health. The pathogenesis of ALI is complex, in which the inflammatory response is a key factor. Studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasomes are involved in ALI through mechanisms such as inflammation induction, increased microvascular permeability, recruitment of neutrophils, oxidative stress, and pyroptosis, playing a key role in the occurrence and progression of ALI. Therefore, regulating NLRP3 inflammasomes and inhibiting the release of inflammatory factors can alleviate the damage in ALI. At present, ALI is mainly treated by mechanical ventilation and oxygen therapy, which have problems such as high costs and poor prognosis. In recent years, studies have shown that traditional Chinese medicine (TCM) can reduce the inflammatory response and the occurrence of oxidative stress and pyroptosis by regulating the NLRP3 inflammasome, thus alleviating the damage and decreasing the mortality of ALI. Based on the relevant literature in recent years, this article reviews the research progress in TCM treatment of ALI by regulating NLRP3 inflammasomes, discusses how NLRP3 inflammasomes participate in ALI, and summarizes the active ingredients, extracts, and compound prescriptions of TCM that regulate NLRP3 inflammasomes, aiming to provide new ideas for the clinical treatment of ALI and the development of relevant drugs.