1.Research on the Role and Clinical Application Value of the Histone H2A Deubiquitinase BAP1 in the Occurrence and Progression of Malignant Glioma Cells
Yufang LI ; Zhifeng LIN ; Ying XIANG ; Fei QI ; Feizhou HAN ; Zhongli QIAN ; Tao WANG ; Xu CHEN
Journal of Modern Laboratory Medicine 2024;39(2):7-11,33
Objective To explore the role of breast/ovarian cancer susceptibility gene 1 associated protein 1(BAP1)in the occurrence and progression of human malignant glioma and the feasibility of BAP1 as a clinical diagnostic marker for malignant glioma.Methods The differential expression of BAP1 in normal and glioma tissue was analyzed based on the GSE4290 and GSE90598 sub-datasets from the gene expression omnibus(GEO)database.Receiver operating characteristic(ROC)curve analysis was conducted to assess the early diagnostic value of BAP1 for malignant glioma.Primary lesion tissues from 28 nonpaired malignant glioma patients and non-tumor brain tissues removed by internal decompression surgery in 5 patients with traumatic brain injury collected independently were collected,and the expression levels of BAP1 were measured using quantitative real-time polymerase chain reaction(qRT-PCR).Specific small interfering RNAs(siRNAs)targeting BAP1 were transiently transfected into U251 cells to further evaluate their interference efficiency.Flow cytometry was employed to analyze changes in the cell cycle and apoptosis of U251 cells with BAP1 knockdown.Results The results of bioinformatics showed that the expression of BAP1 in malignant glioma tissues was lower than that in normal brain tissues(GSE 4290:1 209±18.49 vs 1 476±53.90,GSE 90598:5.19±0.10 vs 5.65±0.21),and the differences were significant(t=5.115,2.267,all P<0.05).ROC curve showed that BAP1 could efficiently differentiate malignant glioma tissue from normal brain tissue(GSE4290:AUC=0.78,GSE90598:AUC=0.75,all P<0.05).The expression level of BAP1 in primary malignant glioma tissue was lower than that in normal brain tissue(0.27±0.04 vs 1.06±0.07),and the difference was significant(t=10.22,P<0.001).After down-regulating the expression of BAP1 in U251 cells,the proportion of S phase cells increased from 17.59%to 27.21%(siBAP1-1)and 25.79%(siBAP1-2),respectively,and the differences were significant(t=6.576,6.642,all P<0.01).However,the apoptosis levels decreased from 10.17%to 2.70%(siBAP-1)and 3.00%(siBAP-2),respectively,and the differences were significant(t=10.31,9.428,all P<0.01).Conclusion Histone H2A deubiquitinase BAP1 could exert the function of tumor suppressor genes by inhibiting rapid cell cycle progression and promoting apoptosis in malignant glioma,and could serve as a potential clinical diagnostic biomarker for malignant glioma.
2.Mechanism of Qinggongtang Against Generalized Anxiety Disorder Based on Glu/GABA Metabolic Balance
Xiaoxiao HUANG ; Zhongli XIE ; Mengyue XIE ; Shengzhen LI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):28-35
ObjectiveTo investigate the therapeutic effect of Qinggongtang in regulating Glu/GABA metabolic balance and the mechanism of its anxiolytic effect on rat models of anxiety. MethodFifty-four rats were randomly divided into normal, model, diazepam (0.225 mg·kg-1), and low-dose, medium-dose, and high-dose groups of Qinggongtang (5.085, 10.17, 20.34 g·kg-1), with nine rats in each group. Except for the normal group, the other groups were subjected to indeterminate vacutainer stress and chronic restraint stress for 12 days to prepare the anxiety model. On the 3rd day of the stress, 10 days of corresponding drug intervention was started. At the end of the drug treatment, the anxiety level of rats in each group was evaluated by the elevated cross maze experiment (EPM) and the light and dark box experiment (LDB), and the effect of Qinggongtang on the anxiety behavior of rats was preliminarily analyzed. The levels of Glu and GABA in the amygdala tissue of the rats were detected by enzyme linked immunosorbent assay (ELISA), and the changes in the synaptic ultrastructure of the amygdala of the rats in each group were observed by electron microscopy. The mRNA expression of glutamic acid decarboxylase (GAD65 and GAD67), glutamine synthetase (GS), and glutamate transporter-1 (GLT-1) in the amygdala were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR), and their protein expression was detected by Western blot. ResultCompared with those in the normal group, rats in the model group showed an obvious anxiety state and dull yellow and lusterless fur. They were irritable, easy to anger, and preferred to curl up in the corner. The number of times the EPM entered the open arm and the residence time in the open arm were significantly reduced (P<0.01), and the residence time in the open box and the number of times the LDB went through the box were significantly reduced (P<0.01). The content of Glu in the amygdala was increased (P<0.01), and the content of GABA was reduced (P<0.01). The value of Glu/GAB was elevated (P<0.01), and the number of synaptic and pre-synaptic membrane vesicles in the amygdala was decreased. Sparse dense material in the post-synaptic membrane, increased synaptic gap, slightly disrupted internal structure, and decreased mRNA and protein expressions of GAD65, GAD67, GS, and GLT-1 in the amygdala were observed (P<0.01). Compared with those in the model group, rats in the medium-dose and high-dose groups of Qinggongtang and the diazepam group had bright fur, sensitive reactions, and more active behavior. The number of times EPM entered the open arm and the residence time in the open arm increased significantly (P<0.01), and the residence time in the open box and the number of times the LDB went through the box increased significantly (P<0.01). The content of Glu in all-dose groups of Qinggongtang and the diazepam group decreased (P<0.05, P<0.01), while GABA content increased (P<0.05, P<0.01). The value of Glu/GABA decreased (P<0.01), and the internal and external synaptic structure of each groups of Qinggongtang and the diazepam group was more complete. Synapses and vesicles were numerous, and the synaptic gap was more clearly defined. The efficacy of the high-dose group of Qinggongtang and the diazepam group was the best, and the mRNA and protein expressions of GAD65, GAD67, GS, and GLT-1 in the amygdala were increased in the high-dose group of Qinggongtang and diazepam group (P<0.05, P<0.01). ConclusionQinggongtang can improve synaptic plasticity and affect the expression of GAD65, GAD67, GS, and GLT-1 in the amygdala of rats to regulate Glu/GABA metabolic balance and thus exert anxiolytic effects.
3.Treatment of the fibular fracture in Degree Ⅱ ankle supination-external rotation injury of the Dias-Tachdjian classification in children
Zhen LIU ; Kan WANG ; Li XU ; Jiazhi GAO ; Wenming LUO ; Xuecheng SUN ; Zhongli ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(5):421-427
Objective:To investigate the necessity of internal fixation of the fibular fracture in the treatment of degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification in children.Methods:A retrospective study was conducted to analyze the data of 69 children with ankle fracture (degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification) who had been treated at Department of Orthopedic Trauma, The People's Hospital of Weifang and Department of Pediatric Orthopedics, Tianjin Hospital from January 2015 to October 2021. There were 41 males and 28 females with an age of (10.1±1.4) years, and 37 left and 32 right sides affected. The patients were divided into 2 groups according to whether internal fixation of the fibular fracture was performed. Group A consisted of 21 cases with fibular internal fixation and group B of 48 cases without fibular internal fixation. The preoperative data, operation time and operation expenses were recorded and compared between the 2 groups. At the last follow-up, the anteroposterior and lateral radiographs of bilateral full length lower limbs and ankle joints were taken; the lateral distal tibial angle (LDTA) and the anterior distal tibial angle (ADTA) on the affected side, and the disparity between bilateral ankle tibiotalar angles were measured; ankle function was assessed according to the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS); the occurrence of premature physeal closure (PPC) was recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.5±4.1) months. At the last follow-up, the LDTA on the affected side was 89.6° (87.9°, 90.5°) in group A and 88.6°±1.9° in group B; the ADTA on the affected side was 80.9° (79.0°, 81.4°) in group A and 80.0° (78.6°, 81.2°) in group B; the disparity between bilateral ankle tibiotalar angles was 1.1°±0.5° in group A and 1.2°±0.5° in group B; the AOFAS ankle-hindfoot score was (89.5±5.2) points in group A and 89.0 (87.0, 92.0) points in group B. There was no statistically significant difference between the 2 groups in the above items ( P>0.05). The incidence of PPC was, respectively, 14.3% (3/21) and 14.6% (7/48) in groups A and B, showing no statistically significant difference ( P>0.05). Conclusions:In the treatment of degree Ⅱ ankle supination-external rotation injury in children, internal fixation of the fibular fracture has no significant effect on the imaging angles or the function of the ankle joint. After anatomic reduction of the distal tibia, the fibular fracture can be treated without internal fixation to reduce operational trauma, shorten operation time and reduce operation expenses.
4.Closed reduction with a self-developed T-frame plus robotic navigation to treat supracondylar humeral fractures of Gartland type Ⅲ in children
Chi TANG ; Zhe BAI ; Ninan QI ; Sitong YUE ; Ye LI ; Zefeng GAO ; Chenglin NIU ; Zhongli ZHANG
Chinese Journal of Orthopaedic Trauma 2024;26(11):985-990
Objective:To study the efficacy of closed reduction with a self-developed T-frame plus robotic navigation in the treatment of supracondylar humeral fractures of Gartland type Ⅲ in children.Methods:A retrospective study was conducted to analyze the data of 67 children with supracondylar fracture of Gartland type Ⅲ who had undergone surgery at The Fifth Hospital of Harbin from January 2023 to March 2024. There were 35 males and 32 females with an age of (5.6±1.2) years. The children were divided into 2 groups according to different surgical methods. The control group (33 cases) was treated by closed reduction and internal fixation with percutaneous K-wire and the study group (34 cases) by closed reduction with a self-developed T-frame plus robotic navigation for internal fixation with percutaneous K-wire. The operation time, anatomical reduction, intraoperative fluoroscopy frequency, intraoperative needle adjustment, Flynn score at the last follow-up and complications were compared between the 2 groups.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All children were followed up for (6.3±2.5) months after surgery. There were no significant differences in operation time, Flynn score at the last follow-up or incidence of complications between the study and the control groups ( P>0.05). The rate of anatomical reduction in the study group (97.1%, 33/34) was significantly higher than that in the control group (54.5%, 18/33), and the intraoperative fluoroscopy frequency [(11.6±2.5) times] and needle adjustment (5.6±1.2) times in the study group were significantly lower than those in the control group [(37.2±2.1) times and (28.7±3.9) times] ( P<0.05). Conclusions:In the treatment of supracondylar humeral fractures of Gartland type Ⅲ in children, our self-developed T-frame can play a good role in fracture reduction and temporary fixation, avoiding iatrogenic secondary injuries caused by freguent reduction and adjustment of needle threading in the course of robotic navigation.
5.Development of five grading standards and visual assessment tools for the elderly disability with dementia and its reliability and validity testing
Cheng CHEN ; Xin JIAO ; Yixiu WANG ; Qin ZHANG ; Xiang LU ; Wenwen LI ; Zhongli JIANG
Chinese Journal of Geriatrics 2024;43(5):616-622
Objective:To establish Chinese grading standards for elderly disability and dementia, in accordance with the International Classification of Functioning, Disability and Health(ICF)items, and to develop visual assessment tools that can be easily understood by patients, family members, and health workers.The aim is to verify the reliability and validity of these tools.Methods:In this study, we established five categories of elderly disability classification, along with corresponding ICF items and visual evaluation tools.The appropriateness and compatibility of the tools were assessed using questionnaires, which included illustrations, GIF dynamic pictures, and ICF items.Correlation analysis was conducted to screen the items, and the validity of the visual evaluation tools was determined through a picture-text matching validity test.Reliability was evaluated using internal consistency or test-retest reliability, and validity was assessed through content validity.Results:Each grade of disability was initially divided into five levels.However, after expert consultations and classification revision, each level was ultimately simplified into four levels with clearer descriptions.The Pearson correlation coefficients between all items and the total scores of each part were found to exceed 0.3, and the difference was statistically significant(all P<0.05).The average and mode of the illustrations and GIF dynamic pictures, when matched with related descriptions, were both above 3, with consistency rates surpassing 50%.Statistical differences were observed in eight items between the two visual assessment tools.The Cronbach's α coefficients, which reflect internal consistency, were all above 0.60.The intra-group correlation coefficients, which indicate test-retest reliability, were all greater than 0.70.The content validity index of the questionnaire at the overall level was above 0.90, while the item-level content validity index was more than 0.78. Conclusions:The Chinese grading standards for elderly disability and dementia, which are aligned with the ICF, have been preliminarily established.Visual assessment tools have also been developed, which demonstrate good reliability and validity.Among the two visual assessment tools, GIF dynamic pictures were found to be more popular and easier to understand.
6.Construction and application of integrated management system for open fund projects in a research center
Zhongli YANG ; Daiping LI ; Jirong YUE ; Birong DONG
Chinese Journal of Hospital Administration 2024;40(5):367-373
Open fund projects play an important role in strengthening discipline construction and enhancing research capabilities. The National Clinical Research Center for Geriatrics of West China Hospital, Sichuan University (hereinafter referred to as the Center) initiated the establishment of open fund projects in 2018. However, due to their strong disciplinary and autonomous nature, as well as the presence of uncertainty, these projects posed new challenges to project management. Therefore, based on the theory of project integration management, the Center has established an integrated management system for open fund projects. This system was achieved by identifying the construction objectives of open fund projects, defining their scope of application, and integrating the four essential elements of project management: execution, processes, control, and support. It ensured standardized execution through organizational and institutional measures, optimized management processes, implemented control through the development of milestone lists, risk registration lists, superior funding lists, and non-performing lists, and integrated technology and platforms as support. The system was implemented since 2020, realizing comprehensive and holistic management of open fund projects across all stages and elements, thereby effectively enhancing management efficiency and quality. As of December 2023, 112 open fund projects have been approved, with a total funding of 31.943 million yuan. These projects have yielded a series of achievements in cohort study and platform construction, academic output, and have demonstrated remarkable effectiveness in projects and talents cultivation. The construction and application of this system can provide reference for medical institutions in managing open fund projects.
7.A predictive model for macrolide unresponsive Mycoplasma pneumoniae pneumonia in children
RAO Rui ; LI Zhixin ; JIA Zhongli ; LI Song ; SONG Liyao ; DONG Wenbin
China Tropical Medicine 2024;24(7):783-
Abstract: Objective To explore the risk factors for macrolide unresponsive mycoplasma pneumoniae pneumonia (MUMPP) in children and to develop a model for predicting the risk of MUMPP. Methods Children with mycoplasma pneumoniae pneumonia admitted to the Pediatric Department of Leshan People's Hospital who met the inclusion criteria from March 1, 2023, to December 1, 2023, were retrospectively selected and divided into the responsive group and unresponsive group according to their reactions to macrolides. General patient data, laboratory tests, and imaging findings were collected and compared. Logistic regression analysis was used to analyze the risk factors of the Macrolide unresponsive mycoplasma pneumoniae pneumonia, and R language (R4.2.3) to establish the nomogram model. The goodness of fit, discriminative ability, calibration, and clinical utility of the model were assessed using the Hosmer-Lemeshow goodness of fit test, receiver operating characteristic (ROC) curve analysis, calibration curve analysis, and decision curve analysis, respectively. Results A total of 224 patients were included in the analysis of children. Among them, 156 (70%) were randomly selected as the training set, and the remaining 68 cases (30%) were used as the validation set. Logistic regression analysis revealed that pleural effusion (OR=6.986, 95%CI 1.362-35.847), highest temperature before admission (OR=3.095, 95%CI 1.487-6.439), neutrophil count (OR=1.294, 95%CI:1.103-1.519), C-reactive protein (OR=1.030, 95%CI 1.002-1.058), and procalcitonin (OR=2.899, 95%CI:1.353-6.214) were independent risk factors for MUMPP in children (all P<0.05). A nomogram was established using R software. The Hosmer-Lemeshow goodness of fit tests for the training set and the validation set were χ2=4.018 and χ2=4.657 (all P>0.05), indicating a good fit of the model. The AUC values for the training set and validation were 0.825 (95%CI: 0.755-0.894) and 0.828 (95%CI 0.729-0.928), respectively, suggesting good discriminative ability of the model. Calibration curve analysis suggested that the model had good predictive performance, while decision curve analysis indicated a high clinical application value of the predictive model. Conclusions Pleural effusion, highest body temperature before admission, neutrophil count, C-reactive protein, and procalcitonin are independent risk factors for MUMPP in children. The prediction model constructed based on the above variables has high predictive efficacy and clinical application value.
8.Screening and identification of a polyurethane-degrading bacterium G-11 and its plastic degradation characteristics.
Zhitong JIANG ; Xue CHEN ; Jinhui LEI ; Huizhen XUE ; Bo ZHANG ; Xiaofan XU ; Huijing GENG ; Zhoukun LI ; Xin YAN ; Weiliang DONG ; Hui CAO ; Zhongli CUI
Chinese Journal of Biotechnology 2023;39(5):1963-1975
Polyurethane (PUR) plastics is widely used because of its unique physical and chemical properties. However, unreasonable disposal of the vast amount of used PUR plastics has caused serious environmental pollution. The efficient degradation and utilization of used PUR plastics by means of microorganisms has become one of the current research hotspots, and efficient PUR degrading microbes are the key to the biological treatment of PUR plastics. In this study, an Impranil DLN-degrading bacteria G-11 was isolated from used PUR plastic samples collected from landfill, and its PUR-degrading characteristics were studied. Strain G-11 was identified as Amycolatopsis sp. through 16S rRNA gene sequence alignment. PUR degradation experiment showed that the weight loss rate of the commercial PUR plastics upon treatment of strain G-11 was 4.67%. Scanning electron microscope (SEM) showed that the surface structure of G-11-treated PUR plastics was destroyed with an eroded morphology. Contact angle and thermogravimetry analysis (TGA) showed that the hydrophilicity of PUR plastics increased along with decreased thermal stability upon treatment by strain G-11, which were consistent with the weight loss and morphological observation. These results indicated that strain G-11 isolated from landfill has potential application in biodegradation of waste PUR plastics.
Plastics/metabolism*
;
Polyurethanes/chemistry*
;
RNA, Ribosomal, 16S
;
Bacteria/genetics*
;
Biodegradation, Environmental
9.Isolation and identification of a polyester-polyurethane degrading bacterium Bacillus altitudinis YX8-1.
Caiting ZENG ; Junbin JI ; Fanghui DING ; Zhoukun LI ; Hui CAO ; Zhongli CUI ; Xin YAN
Chinese Journal of Biotechnology 2023;39(5):1976-1986
Although polyurethane (PUR) plastics play important roles in daily life, its wastes bring serious environmental pollutions. Biological (enzymatic) degradation is considered as an environmentally friendly and low-cost method for PUR waste recycling, in which the efficient PUR-degrading strains or enzymes are crucial. In this work, a polyester PUR-degrading strain YX8-1 was isolated from the surface of PUR waste collected from a landfill. Based on colony morphology and micromorphology observation, phylogenetic analysis of 16S rDNA and gyrA gene, as well as genome sequence comparison, strain YX8-1 was identified as Bacillus altitudinis. The results of high performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that strain YX8-1 was able to depolymerize self-synthesized polyester PUR oligomer (PBA-PU) to produce a monomeric compound 4, 4'-methylene diphenylamine. Furthermore, strain YX8-1 was able to degrade 32% of the commercialized polyester PUR sponges within 30 days. This study thus provides a strain capable of biodegradation of PUR waste, which may facilitate the mining of related degrading enzymes.
Polyurethanes/chemistry*
;
Polyesters/chemistry*
;
Chromatography, Liquid
;
Phylogeny
;
Tandem Mass Spectrometry
;
Bacteria/metabolism*
;
Biodegradation, Environmental
10.A multicenter study of R-ISS staging combined with frailty biomarkers to predict the prognosis and early death in newly diagnosed elderly multiple myeloma patients
Yingjie ZHANG ; Hua XUE ; Mengyao LI ; Jianmei XU ; Xinyue LIANG ; Weiling XU ; Xiaoqi QIN ; Qiang GUO ; Shanshan YU ; Peiyu YANG ; Mengru TIAN ; Tingting YUE ; Mengxue ZHANG ; Yurong YAN ; Zhongli HU ; Nan ZHANG ; Jingxuan WANG ; Fengyan JIN
Chinese Journal of Geriatrics 2023;42(10):1207-1212
Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

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