1.Research Analysis of SLC12A3 Gene Mutation and Molecular Mechanism in Gitelman Syndrome
Chunli WANG ; Bixia ZHENG ; Wei ZHOU ; Ruochen CHE ; Fei ZHAO ; Aihua ZHANG ; Guixia DING
JOURNAL OF RARE DISEASES 2024;3(1):50-56
This study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population. We collected the clinical manifestations, growth and development status, laboratory examination results, and In the 20 patients with Gitelman syndrome, all of them had hypokalemia. We indemnified twenty-six We found the preliminary evidence that the high-frequency mutation D486N in the Chinese population affected the expression of total and membrane-bound NCC protein and influenced the membrane localization of NCC protein. The findings of this study provides experimental evidence for genetic counseling, diagnosis, and treatment of Gitelman syndrome.
2.Mechanism of effect of rosiglitazone on pancreatic cancer in diabetic mice based on impact of PPARy on glucose transport and metabolism
Rui-Ping HU ; Li-Feng SHANG ; He-Jing WANG ; Hong-Xia CHE ; Ming-Liang WANG ; Huan YANG ; Yuan-Yuan JIN ; Fei-Fei ZHANG ; Jian-Ling ZHANG
Chinese Pharmacological Bulletin 2024;40(7):1325-1334
Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P<0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P<0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.
3.Effect of IGFBP6 in unstable carotid atherosclerotic plaque:bioinformatics analysis and experimental validation
Yu-Yan LI ; Ying-Ying LIANG ; Jie-Xin ZHOU ; Fei CHE ; Jin-Xia FU
Medical Journal of Chinese People's Liberation Army 2024;49(6):701-710
Objective To investigate the differentially expressed genes(DEGs)and their molecular interactions in unstable carotid atherosclerotic plaques.Methods Gene expression datasets related to carotid atherosclerotic plaques(GSE41571,GSE118481,and E-MTAB-2055)were downloaded from Gene Expression Omnibus(GEO)and European Bioinformatics Institute(EBI)ArrayExpress databases.The co-regulated DEGs in at least two datasets of unstable carotid plaques were merged and analyzed using Gene Ontology Biological Process(GO-BP),Kyoto Encyclopedia of Genes and Genomes(KEGG),Protein-Protein Interaction(PPI)Networks and subnetwork analysis,relationships between miRNAs/transcription factors and target genes,and drug-gene interaction database.Quantitative real-time PCR(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to detect the expression levels of some DEGs in carotid plaques and plasma from 58 patients with carotid atherosclerosis.Results GO enrichment analysis showed that DEGs in unstable carotid atherosclerotic plaques were mainly enriched in genes related to inflammatory response and extracellular matrix structure genes.KEGG enrichment analysis indicated that upregulated DEGs in unstable carotid plaques were enriched in extracellular matrix receptor(ECM-receptor)interaction,PI3K-Akt,Hippo and transforming growth factor-β(TGF-β)signaling pathways,while downregulated DEGs were primarily enriched in lysosomes,phagosomes,and chemokines processes.PPI network analysis suggested that COL1A2,COL4A2,insulin-like growth factor binding protein 6(IGFBP6),COL4A5,C1QA,CXCL10,CXCL2,CXCR4,and CSF1R may play important roles in PPI networks.Prediction of drug-gene interactions revealed that CSF1R had the most drug interaction,CXCL2 was most antagonized by drugs,and IGFBP6 was most activated by drugs.qRT-PCR showed that the expression level of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.001).ELISA results showed that plasma concentration of IGFBP6 in unstable carotid plaques group was significantly lower than that in stable carotid plaques group(P<0.0001).Receiver operating characteristic(ROC)suggested that the area under the curve(AUC)for plasma IGFBP6 levels to identify unstable plaques was 0.894(95%CI 0.810-0.977),with a cutoff value of 142.08 ng/ml.Conclusion IGFBP6 may become an important biomarker for predicting unstable carotid atherosclerotic plaques.
4.Retrospective analysis of 2 657 serum autoantibodies results detected by multiple methods
Dongli CHE ; Tingxuan CHENG ; Jinlong DU ; Qing LIU ; Ye TIAN ; Lina SHI ; Xiaoning WANG ; Fei XIE ; Yuan GU ; Yanguo TAN
International Journal of Laboratory Medicine 2024;45(23):2838-2843
Objective To investigate the performance of different methods in common autoantibody detec-tion,and to provide basis for the detection strategy of autoantibody.Methods A total of 2 657 cases were in-cluded in this study,whose serum antinuclear antibody(ANA)by indirect immunofluorescence method(IIF)and antinuclear antibody spectrum(ANAs,a total of 15 antibodies)by immunoblot method(IB)were tested simultaneously,and anti-double strand DNA antibody(anti-dsDNA antibody)were tested by IIF,enzyme linked immunosorbent assay(ELISA)and IB.ANCA and ANCA spectrum[anti-myeloperoxidase antibody(anti-MPO antibody),anti-protease 3 antibody(anti-PR3 antibody)]were tested by IIF and ELISA respec-tively in 2 348 cases.Results Firstly,the detection rate of ANA was significantly higher than that of ANAs(57.77%vs.30.64%,P<0.001).Among the specimens detected with ANA,40.78%detected at least one specific antibody positive.Among the specimens detected with ANAs positive,ANA was not detected in 23.10%of cases.Secondly,the ANA positive cases were mainly of lower titers,and cases with titer of ≤1∶320 accounted for 84.95%of the total detected cases.But the higher the titer,the higher the detection rate of ANAs specific antibodies(29.63%in 1∶100,48.56%in 1∶320,77.78%in 1∶1 000,92.42%in≥1∶3 200).Thirdly,among the specimens detected ANAs positive,the composition ratios of anti-Scl-70,anti-PM-Scl and anti-PCNA antibodies in ANA positive cases was significantly lower than those in ANA negative cases(P<0.001).Fourthly,the detection rate of anti-dsDNA antibody by ELISA was the highest(4.14%),which was significantly higher than those by IIF or IB(both P<0.001),and the difference in detection efficacy of the latter two methods was also statistically significant(P<0.001).Even so,the IIF and IB for the detection of anti-dsDNA antibody still had a certain complementary effect on ELISA.Fifthly,the positive rate of ANCA by IIF was significantly higher than that of ANCA spectrum(9.16%vs.2.43%),but among those who were detected anti-MPO antibodies and/or anti-PR3 antibodies positive,47.37%were ANCA negative.Conclusion Different methods for detecting autoantibodies have significantly different detection efficacy,and it is partic-ularly necessary to adopt correct detection strategies based on evidence-based medicine.
5.Clinical analysis of 226 cases of deviated nose with deviated nasal septum treated by endoscopic assisted functional rhinoplasty.
Min CHEN ; Na LI ; Fei CHE ; Shu YAN ; Jun Feng WEN ; Xiao Jun WANG ; Y YUAN ; Y R LI
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58():326-332
Objective: To explore the method and effect of endoscopic assisted functional rhinoplasty for patients with deviated nose and deviated nasal septum, which achieve correction of nasal morphology and ventilation dysfunction. Methods: The clinical data of 226 patients with deviated nose and deviated nasal septum from June 2009 to February 2022 who were treated by endoscopic assisted functional rhinoplasty in the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 174 males and 52 females, with the age ranging from 7 to 67 years old. The effect was evaluated by subjective and objective evaluation methods. SPSS 27.0 software was used for statistical analysis. Results: All patients were followed up for 6 to 24 months, 174 cases were cured (174/226, 76.99%), 52 cases were effective (52/226, 23.01%), and the total effective rate was 100% (226/226). The difference between preoperative and postoperative facial appearance deviation was statistically significant ((6.84±2.25)mm vs (1.82±1.05)mm, t=38.94, P<0.001), and the nasal ventilation function of all patients was improved. Conclusions: Endoscopic assisted functional rhinoplasty for the patients with deviated nose combined with deviated nasal septum has the advantages of clear surgical field, fewer complications, and good result. It can achieve the purpose of simultaneous correction of nasal and ventilation dysfunction, which is recommended for popularizing in clinical application.
6.Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation.
Zhaodi CHE ; Yali SONG ; Chengfang XU ; Wei LI ; Zhiyong DONG ; Cunchuan WANG ; Yixing REN ; Kwok-Fai SO ; George L TIPOE ; Fei WANG ; Jia XIAO
Acta Pharmaceutica Sinica B 2023;13(1):100-112
Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.
7.Preparation and in vitro release of quercetin nanocrystals self-stabilized Pickering emulsion.
Zhe WANG ; Fei HU ; Zhi-Hui CHE ; Qing SONG ; Bao-de SHEN ; Hai-Long YUAN
China Journal of Chinese Materia Medica 2022;47(5):1230-1236
A new quercetin nanocrystals self-stabilized Pickering emulsion(QT-NSSPE) was prepared by high-pressure homogenization combined with probe ultrasonic method. The influences of oil fraction, quercetin(QT) concentration, and pH of water phase on the formation of QT-NSSPE were investigated. On this basis, the QT-NSSPE prepared under optimal conditions was evaluated in terms of microstructure, stability, and in vitro release and the droplet size and drug loading were 15.82 μm and 4.87 mg·mL~(-1), respectively. The shell structure formed by quercetin nanocrystals(QT-NC) on the emulsion droplet surface was observed under a scanning electron microscope(SEM). X-ray diffraction(XRD) showed that the crystallinity of adsorbed QT-NC decreased significantly as compared with the raw QT. There were not significant changes of QT-NSSPE properties after 30 days of storage at room temperature. The in vitro release experiment confirmed that QT-NSSPE has a higher accumulative release rate than the raw QT. All these results indicated that QT-NSSPE has a great stability and a satisfactory in vitro release behavior, which is a promising new oral delivery system for QT.
Emulsions/chemistry*
;
Nanoparticles
;
Particle Size
;
Quercetin
;
Water/chemistry*
8.Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (version 2022)
Zhengwei XU ; Dingjun HAO ; Liming CHENG ; Baorong HE ; Bohua CHEN ; Chen CHEN ; Fei CHE ; Jian CHEN ; Qixin CHEN ; Liangjie DU ; Shunwu FAN ; Zhong FANG ; Shiqing FENG ; Yanzheng GAO ; Haishan GUAN ; Zhong GUAN ; Hua JIANG ; Weimin JIANG ; Dianming JIANG ; Jun JIANG ; Yue JIANG ; Lijun HE ; Yuan HE ; Bo LI ; Tao LI ; Jianjun LI ; Xigong LI ; Yijian LIANG ; Bin LIN ; Bin LIU ; Bo LIU ; Yong LIU ; Zhibin LIU ; Xuhua LU ; Chao MA ; Lie QIAN ; Renfu QUAN ; Hongxun SANG ; Haibo SHEN ; Jun SHU ; Honghui SUN ; Tiansheng SUN ; Jun TAN ; Mingxing TANG ; Sheng TAO ; Honglin TENG ; Yun TIAN ; Jiwei TIAN ; Qiang WANG ; Xinwei WANG ; Jianhuang WU ; Peigen XIE ; Weihong XU ; Bin YAN ; Yong YANG ; Guoyong YIN ; Xiaobing YU ; Yuhong ZENG ; Guoqing ZHANG ; Xiaobo ZHANG ; Jie ZHAO ; Yue ZHU
Chinese Journal of Trauma 2022;38(11):961-972
Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.
9.Expression of cyclophilin A in oral squamous cell carcinoma and its effect on cell proliferation and invasion.
Xiao-Yang XIA ; Fei FANG ; Yan LIU ; Chao CHE ; Jin-Juan KE ; Sheng-Jun JIANG
West China Journal of Stomatology 2021;39(2):164-169
OBJECTIVES:
To investigate the expression of cyclophilin A (CyPA) in oral squamous cell carcinoma (OSCC) and explore the effect of downregulating the expression of CyPA gene on the proliferation and invasion of SCC-25 cells.
METHODS:
A total of 77 cases of patients with OSCC were selected. The expression levels of CyPA proteins in OSCC and adjacent normal tissues were evaluated. SCC-25 cells were cultured and divided into the CyPA interference sequence group, negative control group, and blank group. The expression levels of CyPA mRNA and protein in cells were detected by using real-time fluorescent quantitative polymerase chain reaction and Western blot, respectively. Cell proliferation was detected by using methyl thiazolyl tetrazolium and plate colony formation assays. Cell invasion was detected by using Transwell assay.
RESULTS:
The positive expression rate of CyPA protein in OSCC tissues was 76.62%, which was higher than that in adjacent tissues (
CONCLUSIONS
The CyPA protein is highly expressed in OSCC tissues, and the downregulation of CyPA gene expression in SCC-25 cells can reduce cell proliferation and inhibit cell invasion.
Carcinoma, Squamous Cell/genetics*
;
Cell Line, Tumor
;
Cell Movement
;
Cell Proliferation
;
Cyclophilin A/genetics*
;
Gene Expression Regulation, Neoplastic
;
Head and Neck Neoplasms
;
Humans
;
Mouth Neoplasms/genetics*
;
Squamous Cell Carcinoma of Head and Neck

Result Analysis
Print
Save
E-mail