1.Exploring the Mechanism of Action of Jintiange Capsules in Regulating SMSC-Exos miRNA and Articular Chondrocytes mRNA for the Treatment of Osteoarthritis in Rats Based on Transcriptome
Zhichao WANG ; Xue ZHANG ; Xiaofei ZHANG ; Yajun SHI ; Dongyan GUO ; Fei LUAN ; Bingtao ZHAI ; Junbo ZOU ; Puwei YUAN
Chinese Journal of Modern Applied Pharmacy 2024;41(11):1464-1475
OBJECTIVE
To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology.
METHODS
Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA.
RESULTS
Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA.
CONCLUSION
Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.
2.Exploration of high-quality development of the national regional medical center driven by discipline construction
Shihong LI ; Yebo SHAO ; Yajun HONG ; Alin XUE ; Jianying GU
Chinese Journal of Hospital Administration 2024;40(1):25-29
Discipline construction is the main focus of the high-quality development of public hospitals. The authors elaborated on the practice of Zhongshan Hospital(Xiamen), Fudan University, based on the " double-center" homogenization management, implementing the 123456 strategy of " integrated management and homogeneous development" in discipline construction. The hospital has promoted discipline construction from six aspects: building discipline cluster, promoting talent cultivation, building science and technology innovation platform, precise personnel classification, medical and education collaborative education, and information sharing and support. It has achieved new development goals of filling weak discipline gaps, transforming talent transfusion into hematopoietic, and integrating medical, educational, research and management innovation. However, it also encountered difficulties such as homogenization barrier of discipline construction, shortage of excellent talents, and limited brand influence of superior disciplines. The authors put forward suggestions from three dimensions: deepening homogeneous management, building talent echelon, and increasing publicity, in order to provide experience for the high-quality development of other hospitals.
3.Effect and mechanism of paeoniflorin on LPS-induced bronchial epithelial cell inflammatory response based on NF-κB pathway
Fang HE ; Min DING ; Haining ZHEN ; Yajun CHEN ; Xinxin XUE
Chinese Journal of Immunology 2024;40(7):1387-1391
Objective:To explore the effect of paeoniflorin on LPS-induced bronchial epithelial cell inflammatory response by regulating NF-κB pathway.Methods:BEAS-2B cells were cultured in vitro for paeoniflorin toxicity assay and concentration screening.BEAS-2B cells were divided into control group,LPS group,LPS+CAPE group,LPS+PF group and LPS+CAPE+PF group.Inflammatory responses were induced in BEAS-2B cells using LPS(1 μg/ml),and cell viability was detected by CCK-8 assay after administration of paeoniflorin or CAPE interventions.Apoptosis and cell cycle were detected by flow cytometry.The levels of IFN-γ,IL-4,IL-17C and IL-10 were detected by ELISA.The protein expression levels of p53,Bcl-2,Bax,Cyclin1,NF-κB and p-p65 were detected by Western blot.Results:Paeoniflorin increased cell viability,inhibited apoptosis,increased IFN-γ and IL-10 levels(P<0.01),de-creased IL-4 and IL-17C levels(P<0.01),down-regulated the protein expression levels of p53,Bax,NF-κB and p-p65(P<0.01),and up-regulated the protein expression levels of Bcl-2 and Cyclin1(P<0.01).The effect of paeoniflorin was more significant after the intervention of NF-κB inhibitor CAPE.Conclusion:Paeoniflorin reduces LPS-induced inflammatory factor levels in bronchial epithelial cells by regulating the NF-κB pathway,thereby suppressing the asthmatic inflammatory response.
4.KLF7 in epicardial adipose tissue of coronary heart disease promotes inflammation and adipose differentiation
Yajun Xue ; Wenhua Huang ; Yayan Du ; Yijun Zhou ; Xingxing Dong ; Yutao Wei
Acta Universitatis Medicinalis Anhui 2022;57(2):197-202
Objective :
To explore the epicardial adipose tissue ( EAT) of patients with coronary heart disease , KLF7 stimulates macrophages to secrete inflammatory factors and promotes the differentiation and maturation of adipocytes through the NF⁃κB signaling pathway , and to clarify the mechanism of KLF7 in the occurrence and development of CAD.
Methods :
30 patients with coronary heart disease ( CAD group) and 30 patients without coronary heart disease (non⁃CAD group) were collected , and general data and biochemical indicators were collected. qRT⁃PCR was used to detect the expression levels of KLF7 , APN , IL⁃6 , and TNF⁃α mRNA in EAT. Human THP⁃1 cells were cultured in vitro and induced into M1 type macrophages and 3T3 ⁃L1 preadipocytes. The cells were divied into 3 groups : KLF7 up⁃regulated group ( transfected with KLF7 mimic) , KLF7 down⁃regulated group ( transfected with siRNA knockdown KLF7 ) , NC group ( transfected oligopeptide sequence) , transfected two kinds of cells. qRT⁃PCR was used to detect the expression of APN , MCP⁃1 , IL⁃6 and TNF⁃α mRNA in M1 type macrophages , and the protein expression levels of key factors in the NF⁃κB signaling pathway were detected by Westren blot.
The qRT⁃PCR method was used to detect APN , KLF4 , IL⁃6 , MCP⁃1 mRNA and adipocyte differentiation marker peroxisome proliferator⁃activated receptor⁃γ (PPARγ) in 3T3 ⁃L1 preadipocytes 24 h after transfection. CCAAT/enhancer binding protein α (C/EBPα ) , fatty acid binding protein 4 (FABP4) mRNA relative expression levels , and Westren blot was used to detect protein expression levels.
Results :
Compared with the non⁃CAD group , the expression of CAD group decreased , APN decreased , IL⁃6 and TNF⁃α increased significantly , and the difference was statistically significant (P < 0. 01) . KLF7 was highly expressed in human THP⁃1 derived M1 macrophages induced by inflammatory stimuli (LPS) . In M1 macrophages derived from human THP⁃1 , knocking down KLF7 could inhibit the release of inflammatory factors. Transfection with KLF7 ⁃siRNA could significantly inhibit LPS⁃induced phosphorylation of JNK⁃MAPKs , the level of p⁃p65 and the activation of p ⁃IκBa (P < 0. 05) . In 3T3 ⁃L1 preadipocytes , upregulation of KLF7 increased the expression of adipocyte differentiation markers PPARγ , C/EBPa , FABP4 mRNA , and promoted the differentiation of 3T3 ⁃L1 preadipocytes into adipocytes (P < 0. 05) .
Conclusion
The expression of KLF7 in EAT in CAD patients increases. KLF7 activates the activation of macrophages mediated by the JNK⁃NF⁃KB signaling pathway in EAT , promotes inflammation in EAT in CAD patients , and promotes the differentiation and maturation of adipocytes , thereby promoting the development of CAD. It indicates that KLF7 may be a potential therapeutic target for cardiovascular diseases (such as CAD) .
5.Anti-infection effect of phage and its clinical application
Xue XIONG ; Tao CHEN ; Yajun LIU ; Liting CHENG ; Xingmei WANG ; Huaping LIANG
Chinese Critical Care Medicine 2021;33(4):497-499
In recent years, the problem of bacterial resistance has become more and more serious, which has brought troubles to global public health and medical care. The time and money required to develop new antibiotics is even greater than before. Bacteriophage is a kind of virus that can specifically infect bacteria, fungi, actinomycetes and other microorganisms. Relying on host bacteria to replicate in large numbers, rich species, low research and development cost, the value of anti-infection therapy is very considerable. It is a new generation of biological antimicrobial agents with great potential. This paper briefly describes the sterilization mechanism, progress of research on anti-infection aspect and clinical application of phage, in order to provide reference for phage anti-infection treatment and clinical application.
6.A phenotype-genotype study of X-linked retinoschisis in RS1 mutations
Bo CAI ; Yang LIU ; Shunyu PIAO ; Shaolin WANG ; Wenjing LI ; Lin CHEN ; Tian TIAN ; Yajun XUE ; Wenjuan ZHUANG
Chinese Journal of Experimental Ophthalmology 2020;38(4):322-330
Objective:To describe the characteristics of genotype and phenotype in 3 families with X-linked retinoschisis (XLRS) due to RS1 mutations. Methods:A cross-sectional approach was adopted.Three XLRS families at the Ningxia Eye Hospital from October 2017 to March 2019 were included.Clinical data and peripheral blood of patients and related families were collected and clinically staged were formulated through a comprehensive eye examination.The disease-causing genes screened by panel sequencing underwent conservative analysis, pathogenicity analysis and protein structure prediction by software tools.Analysis of the mutations pathogenicity was performed according to the American College of Medical Genetics and Genomics guidelines.The research was approved by Medical Ethics Committee of the People's Hospital of Ningxia Hui Autonomous Region and followed the Declaration of Helsinki.Written informed consent was obtained from each participant.Results:Total 5 young male patients and 1 middle-aged patient in these three families.The optical coherence tomography(OCT) findings of 5 young patients showed typical macular retinoschisis, which were characterized by stage I of XLRS.One middle-aged patient (Ⅱ-9) showed a stage Ⅲ lesion of macular atrophy.The mutations of c. 668G>A, c.618G>A and exon 1 deletion in RS1 gene were found in the three families.C223 and W206 were verified to be highly conserved in mammals and were predicted to be pathogenic mutations by software and the change of protein structure.Conservation analysis and prediction of protein structure were not performed for the mutation of exon 1 deletion.All the mutations were pathogenic variants according to the ACGM guidelines. Conclusions:Mutations of c. 668G>A/p.C223Y, c.618G>A/p.W206X and exon 1 deletion in RS1 gene are pathogenic mutations in Chinese XLRS families.The combination of Panel sequencing with pathogenicity analysis and protein structure prediction have important effect to diagnosis and identify the causative genes for the hereditary retinal diseases.
7.Establishing a trans-provincial closed-type medical alliance via city-university cooperation: practice and exploration
Alin XUE ; Yebo SHAO ; Yajun HONG ; Shihong LI ; Jianying GU
Chinese Journal of Hospital Administration 2020;36(8):625-628
In response to calls of the state to share high quality medical resources with the primary levels for easier access of the local people to best medical care instead of pouring into tertiary hospitals in metropolitans, Xiamen city joined hands with Zhongshan Hospital of Fudan University to establish Xiamen Hospital affiliated to Zhongshan Hospital of Fudan University in an innovative model of " city-university cooperation and homogeneous management" . Open for full service in January 2018, the hospital is run by Zhongshan Hospital in a closed-type medical alliance, enjoying homogenous management in terms of administrative framework, quality of care, talent training and IT management. Thanks to this practice, the hospital has grown into one of the first pilot units of the national regional medical center program, rapidly upgrading medical service level of Xiamen city and its surrounding regions. This paper highlighted the practice of homogeneous management, and analyzed the challenges and solutions for references of building trans-regional closed-type medical alliances.
8.Clinical characteristics and risk factors of occult pneumonia in advanced elderly patients
Guihua CAO ; Jianbin GUO ; Mingtao XUE ; Fengzhong JIN ; Yajun HAN ; Xiaole HE ; Rong ZHANG ; Wei FU ; Xiaoming WANG ; Wei GE
Chinese Journal of Geriatrics 2019;38(6):640-643
Objective To explore the clinical characteristics and risk factors of occult pneumonia in advanced elderly patients.Methods A total of 170 advanced elderly patients with community-acquired pulmonary infection in geriatric department of Xijing hospital from January 2014 to October 2017 were enrolled.Patients were divided into two groups:the observation group (with occult pneumonia,n=80)and the control group(without occult pneumonia,n =90).Clinical data of patients were collected,and clinical characteristics and related risk factors of occult pneumonia in elderly patients were analyzed.Results There was no statistically significant difference in the positive rate of sputum culture and the distribution of pathogenic bacteria between the two groups (P > 0.05).Gram-negative bacteria predominated in pathogenic bacteria.The hospitalization time was longer in the observation group than in the control group[(17.3 ± 3.0) d vs.(10.3 ± 3.9) d,P < 0.05].The mortality rate was higher in the observation group than in the control group(10.0 % vs.3.3 %,P < 0.05).The age was older in the observation group than in the control group[(87.0± 1.7) years vs.(82.0± 2.4) years,P < 0.05].The incidences of diabetes,Alzheimer's disease,hypothyroidism and long-term bed rest were higher in the observation group than in the control group (P < 0.05).Multivariate logistic regression analysis showed that age (OR =6.93),dementia (OR =4.32),hypothyroidism(OR =4.89) were independent risk factors for occult pneumonia (P < 0.05).Conclusions The pathogenic bacteria in advanced elderly patients with occult pneumonia are mainly gram-negative bacteria.The positive rate of CT scan confirmed-occult pneumonia is much higher than that by chest X-ray.The advanced elderly patients with occult pneumonia have longer hospitalization time and higher mortality rates.Old age,senile dementia and hypothyroidism are independent risk factors for occult pneumonia in advanced elderly patients.
9.The value of CTA in the diagnosis of accessory renal artery
Yajun SHAO ; Hongzhe TIAN ; Hongqiang XUE ; Zhuanqin REN ; Youmin GUO
Journal of Practical Radiology 2017;33(5):765-768
Objective To evaluate the clinical application value of CT angiography(CTA) in detection of the accessory renal artery(ARA).Methods The renal artery CTA in 100 cases was reconstructed retrospectively with volume rendering (VR), multiplanar reconstruction (MPR), maximum density projection (MIP) and curved surface reconstruction (CPR).Results In all 200 kidneys,ARA were 47 with an incidence of 23.5% (47/200).The incidence of ARA in male and female were about 17% and 13%, and there was no significant difference between them.The ARA in the upper pole of the kidney was 25 (53.1%), and in lower pole was 22 (46.9%).It was showed on MIP with a display rate of 100%, on MRP of 93.6%, on VR of 90.4% and on CPR of 85.1%.Conclusion CTA is a safe, rapid, noninvasive and economical method for the diagnosis of ARA.It is helpful for surgical renal operation, interventional therapy and renal transplantation.
10.Evaluation of left ventricular function in patients with dilated cardiomyopathy using vector flow mapping
Yan YANG ; Yuxin ZHANG ; Rong REN ; Yajun ZHANG ; Yilin YANG ; Lijun YUAN ; Yunyou DUAN ; Dan XUE
Chinese Journal of Ultrasonography 2017;26(5):374-380
Objective To observe the blood flow changes of left ventricular cavity and quantify the energy loss (EL) and circulation of left ventricular during systole and diastole in patients with dilated cardiomyopathy(DCM) via vector flow mapping(VFM).Methods Thirty-six healthy volunteers and 32DCM patients were enrolled.According to the severity of mitral regurgitation(MR),DCM patients were divided into two groups.The quantitative parameters,including average energy loss(EL-base,EL mid,EL-apex) and circulation (vortex quantity,vortex area,circulation) were measured in the different periods of VFM imaging mode in apical four-chamber view,apical three-chamber view and apical two-chamber view respectively.The difference of parameters was evaluated between different groups during the different periods.The early transmitral valve blood flow velocity E,the late transmitral valve blood flow velocity A,the ratio of early transmitral valve blood flow velocity to the early diastolic mitral valve velocity E/e,the ratio of early transmitral valve blood flow velocity to the late transmitral valve blood flow velocity E/A and Tei index were derived via dual-Doppler imaging technology.Meanwhile,the correlation between VFM parameters with E,A,E/A,E/e or Tei index was also analyzed.Results ①The level of EL were decreased significantly among EL-mid and EL-apex during early diastole,EL-mid during mid-systole,EL-mid and EL-apex during late-systole (P <0.05),when compared with the control group.The vortex quantity,vortex area and circulation during early diastole and the vortex area and circulation during atrial contraction period were significantly different between two groups (all P < 0.05).As for mid-diastole,only vortex area showed significant difference (P <0).01).(②) When compared with different grades of MR in DCM patients,the level of all segments EL during diastole and EL-base during systole increased with severity of MR(P <0.05).The circulation during diastole also increased with the severity of MR(P <0.05).③The vortex area and circulation had positive correlation with E/e during diastole in all subjects(all P <0.05).The vortex area during atrial contraction period and early diastole had positive correlation with E/A and Tei index in all subjects(r =0.630,0.345,0.468,0.316,0.663,0.264,respectively,allP <0.01).EL-mid during late-systole were negatively correlated with LV end diastolic volume,end systolic volume,but positively correlated with ejection fraction in all subjects(r =0.335,-0.312,0.340,respectively,all P <0.05).While,there was positive correlation between E/A with the basal segment of mid-diastole(r =0.376,P <0.01).Conclusions The visualization of hydromechanics inside the heart of DCM patients could be directly accomplished by VFM,which can provide a new method for diagnosis and evaluation of DCM.


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