1.Exploration of the mechanism of cognitive impairment induced by ketamine in mice based on metabolomics
Tingting LUO ; Xiaoxiao YAO ; Xinyi ZHAN ; Yiru MA ; Ting GAO ; Ying WEI
China Pharmacy 2025;36(12):1436-1441
OBJECTIVE To explore the potential mechanism of ketamine-induced cognitive impairment in mice based on metabolomics. METHODS Male C57BL/6 mice were randomly divided into control group and ketamine group (25 mg/kg), with 12 mice in each group. Each group of mice was intraperitoneally injected with normal saline or corresponding drugs, 4 times a day, for 10 consecutive days. On the last 2 days of drug administration, the cognitive behavior was evaluated by Y maze and novel object recognition test, and the histopathological changes in the prefrontal cortex (PFC) were observed. Ultra-high performance liquid chromatography-tandem mass spectrometry technology was used to analyze the changes of metabolites in PFC, screen for differential metabolites, and perform pathway enrichment analysis. RESULTS Compared with the control group, the morphology of PFC neurons in the ketamine group of mice was inconsistent. There were cavities around the nucleus, and the number of deeply stained cells increased. The mean optical density value of the Nissl staining positive area was significantly reduced, and the alternation rate and discrimination index were significantly reduced (P<0.05 or P<0.01). In the PFC tissue samples of mice of the two groups, there were a total of 114 differential metabolites, including 73 up-regulated and 41 down-regulated metabolites, including glutamine, succinic acid, ketoglutarate, and choline, etc. The differential metabolites mentioned above were mainly enriched in metabolism of alanine, aspartate and glutamate, metabolism of arginine and proline, γ aminobutyric acid synapses, pyrimidine metabolism, cholinergic synapses pathways, etc. CONCLUSIONS Ketamine can induce cognitive impairment in mice. Its neurotoxicity is related to abnormal synaptic transmission and energy metabolism, and neuroimmune regulation disorders.
2.Expression of ZIC5 protein in breast cancer and its relation-ship with clinicopathological characteristics and surgical prognosis
Jian-Ye ZHANG ; Ying MA ; Zhan-Hua QI
Chinese Journal of Current Advances in General Surgery 2024;27(6):458-462
Objective:To explore the relationship between the expression of cerebellar zinc finger structure 5(ZIC5)protein in breast cancer and its clinicopathological characteristics,surgical prognosis.Methods:A total of 128 breast cancer patients,who were admitted to our hospital be-tween June 2016 and December 2017,were enrolled in this study.Immunohistochemistry was employed to assess the expression of ZIC5 protein.The positive expression rate of ZIC5 protein in breast cancer tissues was compared with that in normal surgical margin tissues.Additionally,an analysis was conducted to explore the association between the expression of ZIC5 protein and various clinical pathological characteristics of breast cancer patients,as well as its correlation with prognosis.Results:The positive expression rate of ZIC5 protein in breast cancer tissue was higher than that in normal tissue of resection margin.The postoperative survival rate of breast can-cer patients was 81.37%.TNM stage Ⅲ~Ⅳ,undifferentiated/poorly differentiated,tumor diam-eter ≥ 2 cm,invasion depth T3~T4,lymph node metastasis,ZIC5 protein positive expression were all risk factors for poor prognosis of breast cancer surgery.(RR=4.405,5.153,4.520,2.211,3.137,6.079,P<0.05).The survival rate of patients with negative ZIC5 protein expression in breast cancer tissue was higher than that of patients with positive ZIC5 protein expression(P<0.05).Conclu-sion:The positive expression rate of ZIC5 protein in breast cancer tissue is higher than that in nor-mal tissue of resection margin,and the expression of ZIC5 protein in cancer tissue is related to clinical stage,tumor differentiation,tumor size,invasion depth,and lymph node metastasis.The above indicators are risk factors for poor prognosis of breast cancer surgery.
3.Reference values of carotid intima-media thickness and arterial stiffness in Chinese adults based on ultrasound radio frequency signal: A nationwide, multicenter study
Changyang XING ; Xiujing XIE ; Yu WU ; Lei XU ; Xiangping GUAN ; Fan LI ; Xiaojun ZHAN ; Hengli YANG ; Jinsong LI ; Qi ZHOU ; Yuming MU ; Qing ZHOU ; Yunchuan DING ; Yingli WANG ; Xiangzhu WANG ; Yu ZHENG ; Xiaofeng SUN ; Hua LI ; Chaoxue ZHANG ; Cheng ZHAO ; Shaodong QIU ; Guozhen YAN ; Hong YANG ; Yinjuan MAO ; Weiwei ZHAN ; Chunyan MA ; Ying GU ; Wu CHEN ; Mingxing XIE ; Tianan JIANG ; Lijun YUAN
Chinese Medical Journal 2024;137(15):1802-1810
Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.
4.The Pathogenic Characteristics of the Initial Three Mpox Cases in Hunan Province, China.
Rong Jiao LIU ; Xing Yu XIANG ; Zi Xiang HE ; Qian Lai SUN ; Fu Qiang LIU ; Shuai Feng ZHOU ; Yi Wei HUANG ; Fang Cai LI ; Chao Yang HUANG ; Juan WANG ; Fang Ling HE ; Xin Hua OU ; Shi Kang LI ; Yu Ying LU ; Fan ZHANG ; Liang CAI ; Hai Ling MA ; Zhi Fei ZHAN
Biomedical and Environmental Sciences 2023;36(12):1167-1170
5.Research on rapid detection technology of airborne pathogenic organisms based on up-conversion phosphor technology.
Qiao Yun ZHANG ; Xiu Jun SONG ; Hong Ling OU ; Zhan ZHANG ; Ying Ying MA ; Xin Ru WANG
Chinese Journal of Preventive Medicine 2023;57(4):572-576
Objective: To explore the application of up-conversing phosphor technology (UPT) to detect pathogenic organisms in the air. Methods: The performance of UPT was verified with Staphylococcus aureus, Yersinia pestis and Escherichia coli O157 as simulated strains, including stability, specificity, sensitivity and response time tests; Air particle sampler is used to collect air samples in the field microenvironment test chamber, and UPT is used for detection. At the same time, compared with the traditional culture method, the practicability of UPT is verified. Results: The coefficient of variation in laboratory was 9.62% and 8.02% when the concentration of 107 CFU/ml and 108 CFU/ml were detected by UPT. The results were less than the allowable target, and the detection system had good stability. The specificity of UPT was verified by Staphylococcus aureus. The results showed that no non-Staphylococcus aureus was detected, and the positive detection rate of different kinds of Staphylococcus aureus was 100%. The specificity of the detection system was good. The sensitivity of UPT for detecting Staphylococcus aureus was 104 CFU/ml. Detection sensitivity of Yersinia pestis ≥103 CFU/ml; The detection sensitivity of Escherichia coli O157 is ≥103 CFU/ml, and the response time of UPT to bacteria is within 15 min (all 10 min 15 s). The detection results of bacteria contentration in the air of the on-site microenvironment test cabin by UPT showed that when the concentration of Escherichia coli O157 in the air reached above 104 CFU/m3, the detection results of UPT were positive, and with the increase of air concentration, the numerical concentration measured by UPT showed an upward trend, which was positively correlated with the concentration of bacteria in the air. Conclusion: UPT may be feasible as a rapid method to evaluate the species and contentration of pathogenic organisms in the air.
Humans
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Sensitivity and Specificity
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Technology
6.Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.
Jing YU ; Wen-Zhao YAN ; Xin-Hua ZHANG ; Bin ZHENG ; Wen-Sen PAN ; Zhan YANG ; Hong ZHANG ; Zi-Yuan NIE ; Ying MA ; Yang BAI ; Long ZHANG ; Dan-Dan FENG ; Jin-Kun WEN
Journal of Geriatric Cardiology 2023;20(6):431-447
BACKGROUND:
Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood.
METHODS:
Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.
RESULTS:
In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.
CONCLUSIONS
CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.
7.Construction and validation of a Nomogram model of intracranial infection after neurosurgery
Xiao-Ju MA ; Ying YU ; Yan LU ; Song-Qin LI ; Juan LIU ; Zheng WANG ; Feng ZANG ; Hui-Ping HUANG ; You-Peng CHEN ; Yong-Xiang ZHANG ; Wei-Hong ZHANG ; Zhan-Jie LI
Chinese Journal of Infection Control 2023;22(12):1483-1492
Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96%.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P>0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P<0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.
8. Liraglutide inhibits high glucose-induced cardiomyocyte hypertrophy via modulating autophagy and Na
Zhe ZHANG ; Xing WANG ; Lin-Quan YANG ; Hui-Juan MA ; Zhan-Ying YE
Chinese Pharmacological Bulletin 2023;39(1):43-50
Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K
9.Introduction of a tool to assess Risk of Bias in Non-randomized Studies-of Exposure (2022)
Yuehao SUN ; Xiaoxiao WANG ; Minyue PEI ; Xinjie MA ; Youyou YING ; Siyan ZHAN ; Nan LI
Chinese Journal of Epidemiology 2023;44(9):1454-1461
This article introduces the contents of the latest edition Risk of Bias in Non-randomized Studies-of Exposure (ROBINS-E) published in June 2022 [ROBINS-E (2022)], and gives some examples about its usage. ROBINS-E is a tool for assessing the risk of bias in non-randomized studies-of exposure. Compared with ROBINS-E (2019), ROBINS-E (2022) adds more bias for observational studies, covers a more comprehensive range of bias, and adds the assessment of the external authenticity of the study. ROBINS-E (2022) adds a preliminary evaluation process to improve the efficiency of evaluation. In addition, ROBINS-E (2022) visualizes and instrumentalizes the use of signal problems in the form of path graph, making it more convenient to use. ROBINS-E (2022), although more consideration has been given to the issue of co-exposure, still does not address the problem of effect modification in co-exposure, and there is still room to expand the applicable research.
10.Morphology and distribution characteristics of subchondral bone cysts in the talus based on CT three-dimensional reconstruction
Zhengrui FAN ; Jianxiong MA ; Xingwen ZHAO ; Hongqi ZHAN ; Lei SUN ; Hongzhen JING ; Haohao BO ; Ying WANG ; Xinlong MA
Chinese Journal of Trauma 2022;38(2):125-129
Objective:To analyze the morphology and distribution characteristics of subchondral bone cysts of the talus by CT three-dimensional reconstruction.Methods:A total of 176 patients diagnosed with subchondral bone cyst of the talus after CT scan of the ankle or foot from 2015 to 2020 were retrieved from the imaging report database of Tianjin Hospital, including 77 males and 99 females, aged 14-84 years[(56.1±14.0)years]. After three-dimensional reconstruction of the talus and cyst area by Mimics 20.0 software, an equal 2×2 grid configuration was constructed to divide the domed articular surface into four regions: anteromedial, anterolateral, posteromedial and posterolateral. For subchondral cyst of the talus, area involved under grid localization, gender, age and side of the onset were recorded. The anteroposterior diameter, transverse diameter, depth, surface area and volume of the subchondral bone cyst of the talus were measured.Results:Subchondral cyst of the talus was anteromedial in 131 patients (74.4%), anterolateral in 5(2.8%), posteromedial in 34(19.3%), and posterolateral in 6(3.4%). Subchondral cyst of the talus occurred in the older aged (≥60 years) for 78 patients (44.3%), in the middle aged (45-59 years) for 62(35.2%), in young adults for 32(18.2%), and in preadolescents for 4(2.3%). The age composition of the subchondral cyst of the talus involving the anteromedial, anterolateral, posteromedial and posterolateral regions was 59(49, 64)years, 44(39, 45)years, 61(54, 68)years and 40(22, 58) years, respectively (all P<0.01). There were no statistically significant differences in gender and side of the onset (all P>0.05). The anteroposterior diameter of the subchondral bone cysts located anteromedially, anterolaterally, posteromedially and posterolaterally was (9.7±4.4)mm, (3.5±1.1)mm, (10.3±4.4)mm and (2.1±0.8)mm, respectively; the transverse diameter was (5.4±1.7)mm, (3.9±1.8)mm, (5.9±2.2)mm and (3.4±1.1)mm, respectively; the depth was (7.1±2.4)mm, (3.2±2.2)mm, (8.2±3.0)mm and (3.9±1.9)mm, respectively; the surface area was 156.1(82.6, 198.2)mm 2, 23.0(21.4, 28.9)mm 2, 180.0(75.1, 230.4)mm 2 and 28.0(20.3, 36.7)mm 2, respectively; the volume was 77.1(37.1, 129.1)mm 3, 23.9(14.2, 37.8)mm 3, 104.6(37.7, 157.4)mm 3 and 13.0(10.4, 16.0)mm 3, respectively. When comparing the anteroposterior diameter, transverse diameter, depth, surface area and volume of the subchondral bone cysts in the anteromedial and posteromedial regions with the anterolateral and posterolateral regions, the differences were statistically significant (all P<0.01) except for the transverse diameter of the subchondral bone cysts in the anteromedial region and the anterolateral region ( P>0.05). In addition, the depth of subchondral bone cysts in the anteromedial region was significantly greater than that in the posteromedial region ( P<0.05). Conclusions:Subchondral bone cysts of the talar are commonly found in the middle- and old-aged population. Anteromedial lesions of the talar dome are the most commonly seen, with large and deeply involved cysts, followed by posteromedial lesions of the dome, while anterolateral and posterolateral lesions of the dome are less common and have smaller cyst sizes. An equal 2×2 grid configuration for talar cysts is useful in positioning and characterizing bone cysts, and can assist clinicians in accurately diagnosing and treating bone cysts.

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