1.Molecular mechanisms of Ca2+-induced pyroptosis and adhesion changes of HK-2 cells in the formation of calcium-containing kidney stones
Jinjie XIANG ; Maoxin LYU ; Mengyue WANG ; Kun ZHANG ; Hao LI
Tianjin Medical Journal 2024;52(3):250-255
Objective To investigate the possible role and mechanism of activation of pyroptosis classical pathway and alterations in cell adhesion in calcium-containing kidney stones after the action of high concentration of Ca2+ on HK-2 cells.Methods HK-2 cells were cultured in the presence of different concentrations of CaCl2(0,0.1,0.5,1.0,2.0,4.0 and 8.0 g/L)for 24 hours,and cell counting Kit-8(CCK-8)and flow cytometry were used to determine the optimal treatment concentration.Subsequently,the ultrastructure of renal tubular epithelial cells under high Ca2+ condition was observed by transmission electron microscopy after Ca2+ treatment.DCFH-DA staining was used to detect intracellular reactive oxygen species production,and quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot analysis were performed to examine the expression of pyroptosis-related proteins NLRP3,Caspase-1,gasdermin D(GSDMD),adhesive molecules osteopontin(OPN)and CD44 at mRNA and protein levels after high concentration Ca2+ treatment.The expression levels of pyroptosis-related inflammatory factors interleukin(IL)-1β,IL-18 and adhesive molecule monocyte chemotactic protein-1(MCP-1)were detected by enzyme-linked immunosorbent assay(ELISA)after high Ca2+ stimulation.Results Ca2+ showed cytotoxicity for HK-2 cell growth and can promote apoptosis.The higher the Ca2+ concentration,the more toxicity and apoptosis rate for HK-2 cell growth.High concentration of Ca2+ can promote pyroptosis-like morphological changes in HK-2 cells,including loss of cell membrane integrity,release of contents and numerous intracellular vacuoles.Compared with the control group,the expression levels of ROS were sequentially increased in the 1.0 g/L CaCl2 group and the 2.0 g/L CaCl2 group,and the expression levels of pyroptosis-related genes NLRP3,Caspase-1,GSDMD,and the pyroptosis-associated inflammatory factors IL-1β and IL-18,as well as the adhesion molecules OPN,CD44 and MCP-1 were significantly increased(P<0.05).Conclusion High Ca2+ treatment can cause oxidative stress damage in HK-2 cells to produce ROS,which activates NLRP3 inflammasome,leads to the activation of the classical pathway of pyroptosis and increase the adhesion of cells,and ultimately leads to the formation of kidney stones.
2.Risk factors for bronchial asthma in children with allergic rhinitis
YE Maoxin, LIU Chuanhe, SHA Li, GU Qinglong, ZHAO Jing
Chinese Journal of School Health 2021;42(9):1302-1305
Objective:
To explore the risk factors of bronchial asthma in children with allergic rhinitis, and to provide evidence for the early diagnosis, treatment and prevention of asthma in children with allergic rhinitis.
Methods:
Children with allergic rhinitis and children with allergic rhinitis and asthma, who attended the Allergy Clinic of the Capital Institute of Pediatrics from November 2019 to October 2020, were recruited for the study. Medical history, clinical characteristics, allergen types and risk factors were collected and analyzed.
Results:
A total of 117 children with allergic rhinitis and 111 children with allergic rhinitis that subsequently developed into asthma were included. The results of the univariate analysis showed that the occurrence of asthma in children with allergic rhinitis was associated with the course of rhinitis, severity of rhinitis, type of rhinitis, seasonal onset, history of pet contact, family history of allergic diseases, mold, ragweed, dermatophagoides culinae and dust mite sensitization( χ 2=6.15, 8.79, 3.99, 9.44, 5.17, 4.43, 8.48, 10.38, 6.18, 5.31, P <0.05). The Logistic regression analysis showed that rhinitis severity( OR = 7.03 ), family history of allergic diseases( OR =8.24), mold( OR =5.19), and household dust mite sensitization ( OR =25.25) were positively correlated with the occurrence of asthma in children with allergic rhinitis( P <0.05), and dust mite sensitization was the strongest risk factor.
Conclusion
The development of asthma in children with allergic rhinitis is affected by many factors, among which the severity of rhinitis, family history of allergic diseases and dust mite sensitization are the most important factors.
3.Autosomal recessive dyskeratosis congenita: a case report and TERT gene mutation analysis
Maoxin HUANG ; Jianbin YU ; Lina LIU ; Xiaohong LI ; Jiang′an ZHANG
Chinese Journal of Dermatology 2020;53(11):875-879
Objective:To report a case of autosomal recessive dyskeratosis congenita, and to detect mutations in its causative genes.Methods:Peripheral blood samples were collected from the proband and her parents, genomic DNA was extracted, and 100 unrelated healthy individuals served as controls. The Illumina Nextseq500 sequencer was used to detect sequence variations in coding regions of exons of the skin disease-related genes in the proband′s family, and the causative mutation was verified by PCR-Sanger sequencing. The conservation and pathogenicity of gene mutation sites and corresponding protein structure changes were predicted by using bioinformatics softwares Clustalw2.0, PyMOL, PolyPhen-2, SIFT and FATHMM.Results:The proband clinically presented with reticular poikilodermatous patches on the neck and chest, punctate pigmentation on the axilla, atrophy of some toenails, rough skin and oral leukoplakia, accompanied by abnormality in some indicators of routine blood tests and liver function. Genetic testing showed that the proband carried compound heterozygous mutations c.2452G>A (p.Val818Met) and c.2594G>A (p.Arg865His) in the TERT gene, and the c.2452G>A mutation was not included in the Human Gene Mutation Database. The proband′s mother carried a heterozygous mutation c.2452G>A, and no mutation was identified in the TERT gene of her father or 100 healthy controls. Bioinformatics analysis showed that the amino acid positions 818 and 865 of TERT proteins in multiple species were highly conserved and completely conserved respectively, and the corresponding protein structures changed after the above gene mutations. Based on the clinical manifestations, genetic testing, auxiliary examinations, and bioinformatics analysis results, the patient was finally diagnosed with autosomal recessive dyskeratosis congenita.Conclusion:The compound heterozygous mutations c.2594G>A (p.Arg865His) and c.2452G>A (p.Val818Met) in the TERT gene may be responsible for the clinical phenotype of the proband.
4. Mechanism of immune inflammation after severe trauma and progress in clinical intervention
Cong CHEN ; Fan WU ; Maoxin QIN ; Zhongqi LIU ; Chengzhou CAI ; Sheng WANG ; Ruolan LIN ; Yan YAN ; Yi LI ; Minghua LIU
Chinese Journal of Trauma 2019;35(10):953-960
The pathophysiological process of immune inflammatory response after severe trauma is extremely complex, especially manifested in the dynamic changes. In the physiological response state, the inflammatory and anti-inflammatory conditions are in a dynamic balance. The immune inflammatory response is relatively stable, avoiding excessive inflammatory reactions or immunosuppression and reducing further damage to the body. In the pathological response state, the dynamic balance between inflammatory and anti-inflammatory is broken, and it can also lead to persistent inflammatory-immunosuppression-catabolism syndrome (PICS). As a result, it increases serious complications such as uncontrolled inflammatory reactions, sepsis, multiple organ dysfunction syndrome (MODS), and multiple organ failure (MOF). Current researches on post-traumatic immune inflammatory response have also expanded to the genetic level, indicating that the over-expression of genes and the generation and increase of immune response media are likely to be the key reasons for the disorder of immune inflammatory response. The author reviews the research progress of immune inflammatory response mechanism and related clinical intervention after severe trauma, in order to summarize the previous research results and explore the future research direction.
5.Problems Encountered in Revaluation of the Curative Effect of Chinese Patent Medicine and Their Solutions
Peihong QIN ; Xuejiao XI ; Jiyu ZHENG ; Weili LI ; Maoxin LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(2):197-202
Enterprise and competent department in China start to explore evaluation method and technique,as revaluation of Chinese patent medicine has been paid high attention in recent years.However,many problems of Chinese patent medicine standard itself commonly have been neglected in the revaluation of curative effect.This review comprehensively analyzed problems have to be faced in the revaluation of the curative effect of Chinese patent medicine,such as excessive broad expressions of function and indication,obscure definition of indication,identification between function and indication,correspondence of diseases and syndromes between Chinese and western medicine,feasibility of clinical trials,with the provision of general methods and solutions.
6.New Chinese Medicine Methodology of One Research Path——"from Experiment to Clinical Verification" on Key Technology of Translational Medicine
Hong ZHANG ; Jialin DU ; Ying ZHANG ; Maoxin LIANG ; Yv GAN ; Guanghan WANG ; Min QIAO ; Guixin ZOU ; Shaojie XIANG ; Xianhua LI ; Xianmin YOU ; Yinglan FAN ; Xiaolin WU ; Lei ZHAO ; Guoxin LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(4):542-548
Translational medicine means that to establish a bridge between fundamental research and clinical medicine through bidirectional translation path in order to promote the translation and application from fundamental research to clinical medicine.The purpose of traditional Chinese medicine (TCM) translational model is to collate and build one multidimensional TCM translational model,rationality carry out the research on TCM translation.Three paths have been confirmed,where are from literature research to clinical verification,from clinical application to clinical verification,and from experiment to clinical verification.In this research,methodology of one path mcntioned above could be established,which is the key technology of translational medicine.Take constipation,insomnia,and post-flu cough as target diseases to investigate the herbal compounds which could be qualified for clinical application based on preliminary work.This research not only provided clinical data to TCM translation,but also established one methodology of TCM translation path--"from experiment to clinical verification".
7.Points for Attention in the Development of Innovative Chinese Medicine
Guoxin LI ; Ying ZHANG ; Xianmin YOU ; Maoxin LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(9):1419-1423
Based on the innovation of modern science and technology and concepts,the study of innovative Chinese medicine research has not been divorced from the traditional thinking of natural medicine research,in the theoretical system of traditional Chinese medicine,there was basically no inheritance and lack of innovation,which made the research of new medicine of traditional Chinese medicine fall into an awkward position.We sum up our experience in 1 1th Five-Year and 12th Five-Year,combined with the upcoming 13th Five-Year of the research and development idea of component Chinese Medicine,analyzed the impact of 3 aspects on the modernization of Chinese traditional medicine and put forward the solving methods.① The scientific screening of high-level candidate prescriptions has always been the bottleneck of the development of new Chinese medicine and the basic premise of modernization of Chinese Medicine;② It is an important outlet and measure to promote the modernization of traditional Chinese medicine to vigorously carry out the research on the transformation of traditional Chinese medicine and to formulate a scientific and rational mode of transformation of traditional Chinese medicine;③ From the point of view of the development and reform of component traditional Chinese medicine,it is necessary to follow the basic theory of traditional Chinese medicine,and comprehensively to consider the characteristics of the components of Chinese medicine,and to lay the foundation for the screening and research and development of Chinese herbal medicines
9.Investigation and Analysis on Potential Function of Euodia rutaecarpa
Ran LI ; Liping LIU ; Maoxin LIANG
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(11):2410-2414
Through the investigation on functions of E.rutaecarpain ancient herbal literatures,ancient prescriptions and the Chinese Pharmacopoeia(2010 edition),it showed that the basic function of E.rutaecarpa recorded in herbal literatures through dynasties was similar to that of the Chinese Pharmacopoeia.However,the disappearance of Euodia rutaecarpa's functions in the Chinese Pharmacopoeia were dampness-eliminating,blood-activating,spleen-invigorating,phlegm-eliminating,wind-dispelling,and guiding fire to its source,which had been recorded in ancient herb literatures.ThePu-Ji-Fang database management system contained prescriptions with Euodia rutaecarpa in the treatment of asthenia,Bi syndrome,stroke,scabies,edema,phlegm,leukorrhagia,epigastric pain,menoxenia,lochiostasis,fractures,sore,aphtha,and etc,which were absent from the Chinese Pharmacopoeia.In conclusion,we preliminarily confirmed that Euodia rutaecarpahad potential functions in activating blood to resolve stasis,dispelling wind and eliminating dampness,nourishing deficiency and invigorating the spleen,resolving toxins,relieving cough and eliminating phlegm,soothing liver to stop wind,as well as stopping bleeding.
10.Primary Causes of Difficulties in Application of Microcosmic Syndrome Differentiation
World Science and Technology-Modernization of Traditional Chinese Medicine 2014;(11):2314-2319
Since the theory of microcosmic syndrome differentiation was put forward in 1986, Chinese medicine academia has been unremittingly exploring this theory. Efforts were made to explain the syndrome in Chi-nese medicine with objective index of modern medicine, so that different syndromes of the same disease can be rec-ognized on the quantitative view and then apply syndrome differentiation with objective index. This paper compre-hensively analyzed and got the primary causes why microcosmic syndrome differentiation was difficult to apply. It in-cluded no-identical criterion, research design such as the choice of syndrome, reference syndrome, objective index and microcosmic level. Additionally, too many virtual syndromes resulting from applying syndrome differentiation on western medicine diseases existed widely. Consequently, it is extremely urgent that solve these problems and regulate the research thought.


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