1.Identification of the polymorphs of clopidogrel bisulfate based on the steric morphology parameters of crystals.
Long CHEN ; Liuyi WANG ; Xianzhen YIN ; Jincan WANG ; Ruihao LIU ; Dan WANG ; Haiyan LI ; Weifeng ZHU ; Jiwen ZHANG
Acta Pharmaceutica Sinica 2013;48(9):1459-63
The crystal form of solid substance had intrinsic correlation with its three dimensional crystal morphology. Based on the characterization of the three dimensional crystal morphology of clopidogrel bisulfate, this research is to establish a model based on the three dimensional morphological parameters. The granular samples composed of polymorphs of clopidogrel bisulfate and microcrystalline cellulose (MCC) were scanned by synchrotron radiation X-ray microscopic CT technology (SR-microCT) and the three dimensional structural models for which were constructed. Seven groups of three dimensional morphological parameters were calculated. Finally, the mathematical model was established with the multi-layer perception (MLP) artificial neutral network methods to identify and predict the polymorphs of clopidogrel bisulfate. The success rate of the model prediction for the polymorphs of clopidogrel bisulfate was 92.7% and the area under the ROC curve was 96.2%. The polymorphs of drugs could be identified and predicted through the numerical description of the three dimensional morphology. The volume, number of the vertices and the surface area were the major determinants for the identification of the polymorphs of clopidogrel bisulfate.
2.Novel mutations p.Lys327X and p.Leu424CysfsX8 underlying congenital factor Ⅺ deficiency.
Miaoshan WENG ; Fen LIN ; Jincan ZHANG ; Jiaoren WU ; Shaoyi XING ; Liye YANG
Chinese Journal of Medical Genetics 2019;36(8):801-804
OBJECTIVE:
To analyze the phenotype and genetic mutations in a pedigree affected with factor Ⅺ (FⅪ) deficiency.
METHODS:
Activated partial thromboplastin time (APTT), FⅪ activity (FⅪ:C) and FⅪ antigen (FⅪ:Ag) were determined for the proband and his family members. All exons and exon-intron boundaries of the FⅪ gene of the proband were analyzed by direct sequencing. Suspected mutation was verified in his family members.
RESULTS:
The proband had APTT of 82.4 s, FⅪ:C of 0.8%, and FⅪ:Ag of <1%. DNA sequencing showed that he has carried c.1033A>T (Lys327X) mutation in exon 10 and c.1325delT (Leu424CysfsX8) mutation in exon 12 of the FⅪ gene. His elder sister, son, daughter, two granddaughters and one grandson were heterozygous carriers of the c.1033A>T mutation, while his older sister and younger brother were heteozygous carriers of the c.1325delT mutation. Analysis using Mutation Taster software showed that both p.Lys327X and p.Leu424CysfsX8 may affect the function of protein and lead to the corresponding disease.
CONCLUSION
The novel mutations of Lys327X and Leu424CysfsX8 of the the FⅪ gene probably underlie the pathogenesis of congenital coagulation factor Ⅺ deficiency in this pedigree.
Exons
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Factor XI
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genetics
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Factor XI Deficiency
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genetics
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Female
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Heterozygote
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Humans
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Male
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Mutation
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Pedigree
3.Research advances in tibial insertion of posterior cruciate ligament and location of tibial tunnel
Zhen CHEN ; Lingpeng JIN ; Jian ZHANG ; Jincan ZHANG ; Yunxiao WANG ; Jiangtao DONG
Chinese Journal of Orthopaedic Trauma 2022;24(7):640-644
Posterior cruciate ligament (PCL) plays an important role in maintaining the stability of knee. PCL injury is often accompanied by serious axial and rotational instability, and severe PCL injury is likely to be combined with injuries to the anterior cruciate ligament, medial collateral ligament and other tissues which are often repaired by necessary posterior cruciate ligament reconstruction (PCLR) to restore their physiological functions. However, PCLR research is not as common as the research into the anterior cruciate ligament reconstruction, not only due to controversies in the anatomy and mechanics of PCL but also due to a higher failure rate and more complications following PCLR. This situation is closely related to the anatomical characteristics of the PCL tibial insertion. The present review deals with the anatomy, mechanics and clinical research of the PCL tibial insertion in order to provide more references for PCLR operators.
4.Working memory deficits in Parkinson's disease mouse model
Tingting ZHAO ; Huating GU ; Miao ZHAO ; Tianzhi CHEN ; Yingjie AN ; Xian ZHANG ; Jincan HOU ; Peng CAO ; Linghui ZENG ; Chengyu LI
Chinese Journal of Pharmacology and Toxicology 2023;37(7):517-518
OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.
5.Construction of a prognostic prediction model for invasive lung adenocarcinoma based on machine learning
Yanqi CUI ; Jingrong YANG ; Lin NI ; Duohuang LIAN ; Shixin YE ; Yi LIAO ; Jincan ZHANG ; Zhiyong ZENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):80-86
Objective To determine the prognostic biomarkers and new therapeutic targets of the lung adenocarcinoma (LUAD), based on which to establish a prediction model for the survival of LUAD patients. Methods An integrative analysis was conducted on gene expression and clinicopathologic data of LUAD, which were obtained from the UCSC database. Subsequently, various methods, including screening of differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Gene Set Enrichment Analysis (GSEA), were employed to analyze the data. Cox regression and least absolute shrinkage and selection operator (LASSO) regression were used to establish an assessment model. Based on this model, we constructed a nomogram to predict the probable survival of LUAD patients at different time points (1-year, 2-year, 3-year, 5-year, and 10-year). Finally, we evaluated the predictive ability of our model using Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves. The validation group further verified the prognostic value of the model. Results The different-grade pathological subtypes' DEGs were mainly enriched in biological processes such as metabolism of xenobiotics by cytochrome P450, natural killer cell-mediated cytotoxicity, antigen processing and presentation, and regulation of enzyme activity, which were closely related to tumor development. Through Cox regression and LASSO regression, we constructed a reliable prediction model consisting of a five-gene panel (MELTF, MAGEA1, FGF19, DKK4, C14ORF105). The model demonstrated excellent specificity and sensitivity in ROC curves, with an area under the curve (AUC) of 0.675. The time-dependent ROC analysis revealed AUC values of 0.893, 0.713, and 0.632 for 1-year, 3-year, and 5-year survival, respectively. The advantage of the model was also verified in the validation group. Additionally, we developed a nomogram that accurately predicted survival, as demonstrated by calibration curves and C-index. Conclusion We have developed a prognostic prediction model for LUAD consisting of five genes. This novel approach offers clinical practitioners a personalized tool for making informed decisions regarding the prognosis of their patients.