1.Effects of physical exercise on object recognition memory in adult rats of postnatal isoflurane exposures
Xiaoyan FANG ; Mengmeng LI ; Jiwei HAO ; Jing YANG ; Chenqi DENG ; Qinghong ZHANG ; Jiaguang TANG
Medical Journal of Chinese People's Liberation Army 2017;42(7):617-622
Objective To investigate effects of physical exercise (PE) on object recognition memory in adult rats of postnatal isoflurane (Iso) exposures.Methods One hundred and ten postnatal 7-day SD rats (P7) were randomly divided into four groups: normal control group (Naive), Naive+PE group (received physical exercise in P21: a treadmill exercise 30min each day, 5 times/week, for 6 weeks), Iso group (three times of 2-hour Iso exposure in P7, P9, and P11), and Iso+PE group (received PE in P21 after postnatal Iso exposures). In P67, behavioral testing was conducted including open field and object recognition task (ORT), recording the time (Discrimination Ratios, DR) that rats spent on exploring each object, evaluating effects of PE on object recognition memory.Results There was no significant difference in influence of PE on open field testing in all of the groups (P>0.05). Compared with Naive, there was no group difference in DR (P>0.05) for all groups, but the DR of Iso male rats was significantly higher than that of Naive female rats in P67, with significant difference (P=0.034). Compared with non-PE groups, whether or not postnatal Iso exposures, the DR of PE male groups was significantly higher (compared with Naive and Iso group:P67,P=0.050,P=0.017; P95,P=0.037,P=0.019); in female rats, the DR for ISO+PE group was lower than that of Iso group in P67 (P=0.036), but the DR of Naive+PE group was higher than that of Naive group in P95 (P=0.004). Compared with male rats, the DR of non-PE female rats was significantly higher in P67 (vis. Naive and Iso group:P=0.022,P=0.011); but in P95, the DR of non-Iso female groups was significantly higher than that of male groups (vis. Naive and Naive+PE:P=0.008,P=0.017).Conclusions There is no obvious impact of postnatal Iso exposures on object recognition memory of adult rats. These Results also indicate that postnatal PE could improve object recognition memory of non-spatial learning in adult rats. In addition, exercise benefits have gender differences.
2.Risk factors and prognosis of bloodstream infection in the ICU patients
Yiyu DENG ; Fengcai SHEN ; Qiongyu LIN ; Mengmeng CHEN ; Cheng SUN ; Hongke ZENG
Chinese Journal of Emergency Medicine 2015;24(12):1425-1429
Objective To investigate the risk factors and prognosis of blood stream infection in patients of intensive care unit (ICU).Methods Clinical data of all patients with culture-positive sepsis were collected from all ICUs of Guangdong General Hospital from October 12th, 2012 to December 1st, 2014 for retrospective study.Physiological characteristics and laboratory data were compared between patients with blood culture-positive sepsis group and patients without sepsis of control group.Logistic regression analysis was made to identify the risk factors for blood stream infection.Patients with blood culture-positive sepsis group were further divided into survivor and non-survivor groups according to the clinical outcomes.Physiological and laboratory data were compared between two groups.Logistic regression analysis was also performed to identify the risk factors for mortality.Results There were 299 patients with positive blood culture sepsis admitted in the ICUs in two years.Of them, 250 patients infected with Gram positive cocci including staphylococcus haemolyticus, staphylococcus epidermidis, staphylococcus capitis and staphylococcus aureus accounting for the majority.There were 174 patients infected with Gram negative bacilli including acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniaesubsp.pneumoniae accounting for the majority.A univariate analysis demonstrated that there were significant differences in hypertension (P =0.001), diabetes (P =0.01), coronary heart diseases and heart failure (P =0.000), chronic renal insufficiency (P =0.000), prolonged mechanical ventilation (P =0.000), pre-admission intravenous administration of antibiotics (P =0.000), and hypoalbuminemia (P =0.008) between culture positive group and control group.A logistic regression analysis demonstrated that diabetes [OR =2.158, 95% CI (1.230, 3.787), P =0.007], chronic renal insufficiency [OR =13.410, 95% CI (1.715, 104.879), P =0.013], pre-admission intravenous administration of antibiotics [OR =8.375, 95% CI (5.267, 13.317), P=0.000] were independent risk factors for bloodstream infections in ICU.In patients with positive blood culture, the non-survivor group had patients with higher advance of old age, higher rate of hypertension, coronary heart diseases or congestive heart failure, tumor and chronic renal insufficiency, prolonged mechanical ventilation and higher incidence of surgery and pre-admission intravenous administration of antibiotics compared with the survivor group.The advance of old age [OR =1.023, 95% CI (1.008-1.037), P =0.002], prolonged mechanical ventilation [OR =1.055, 95% CI (1.024, 1.088), P =0.000] and hypoalbuminemia [OR =0.933, 95% CI (0.898, 0.971), P =0.001] were independently associated with mortality of bloodstream infection in ICU.Conclusions Diabetes, chronic renal insufficiency and pre-admission intravenous administration of antibiotics were associated with the development of blood stream infection in ICU.The advance of old age, prolonged mechanical ventilation and hypoalbuminemia were independent risk factors for mortality in patients with culture-positive sepsis in ICU.
3.Analysis of microbial characteristics and predisposing factor in gram-negative bacteria blood stream infection
Yiyu DENG ; Fengcai SHEN ; Qiongyu LIN ; Mengmeng CHEN ; Cheng SUN ; Hongke ZENG
The Journal of Practical Medicine 2016;32(4):551-555
Objective To investigate microbial characteristics and predisposing factors in gram-negtive bacteria blood stream infection. Methods A descriptive retrospective study was conducted. Patients diagnosed as sepsis with blood culture of G- bacilli and without sepsis were enrolled. The patients were all admitted to ICUs of Guangdong General Hospital from October, 2012 to December, 2014. The clinical characteristics and outcomes were compared. Multiple logistic regression was used to analyse the predisposing factors for sepsis of G- bacilli. Results A total of 148 patients suffered from sepsis of G-bacilli including Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae were enrolled. Single-factor analysis showed that patients with sepsis of G- bacilli infection had older ages, higher incidence of coronary heart diseases or congestive heart failure, cerebrovascular diseases or chronic renal insufficiency, hypertension, also higher incidence of longer length of hospital stay before blood was drawn for culture, and higher incidence using of vasoactive agents and pre-admission intravenous antibiotics and lower plasma albumin level (P < 0.05). Conclusions Coronary heart disease or congestive heart failure, chronic renal insufficiency and pre-admission intravenous antibiotics were independent predisposing factors for sepsis of G-bacilli.
4.A new unconventional HLA-A2-restricted epitope from HBV core protein elicits antiviral cytotoxic T lymphocytes.
Lu SUN ; Yu ZHANG ; Bao ZHAO ; Mengmeng DENG ; Jun LIU ; Xin LI ; Junwei HOU ; Mingming GUI ; Shuijun ZHANG ; Xiaodong LI ; George F GAO ; Songdong MENG
Protein & Cell 2014;5(4):317-327
Cytotoxic T cells (CTLs) play a key role in the control of Hepatitis B virus (HBV) infection and viral clearance. However, most of identified CTL epitopes are derived from HBV of genotypes A and D, and few have been defined in virus of genotypes B and C which are more prevalent in Asia. As HBV core protein (HBc) is the most conservative and immunogenic component, in this study we used an overlapping 9-mer peptide pool covering HBc to screen and identify specific CTL epitopes. An unconventional HLA-A2-restricted epitope HBc141-149 was discovered and structurally characterized by crystallization analysis. The immunogenicity and anti-HBV activity were further determined in HBV and HLA-A2 transgenic mice. Finally, we show that mutations in HBc141-149 epitope are associated with viral parameters and disease progression in HBV infected patients. Our data therefore provide insights into the structure characteristics of this unconventional epitope binding to MHC-I molecules, as well as epitope specific CTL activity that orchestrate T cell response and immune evasion in HBV infected patients.
Adult
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Amino Acid Sequence
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Animals
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Binding Sites
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Epitopes
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chemistry
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immunology
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metabolism
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Female
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Genotype
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HEK293 Cells
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HLA-A2 Antigen
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metabolism
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Hepatitis B Core Antigens
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chemistry
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immunology
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metabolism
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Hepatitis B virus
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genetics
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metabolism
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Humans
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Hydrogen Bonding
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Male
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Middle Aged
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Molecular Dynamics Simulation
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Mutation
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Protein Binding
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Protein Structure, Tertiary
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T-Lymphocytes, Cytotoxic
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immunology
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metabolism
5.Influence of whole-brain irradiation by X-ray in capillaries and blood-brain barrier in mouse brains
Zhezhi DENG ; Haiwei HUANG ; Mengmeng WU ; Guoyong HE
Chinese Journal of Neuromedicine 2015;14(5):454-459
Objective To investigate the possible presence of radiation brain injury (RBI) in vascular injury and blood-brain barrier (BBB) damage.Methods Seventy 8 weeks old male BALB/C mice were randomly divided into irradiation group and control group;mice in the two groups received whole-brain exposure with a single dose of 10 Gy irradiation or sham irradiation.Tissue samples were taken 1,7,30,90 and 180 days after irradiation (7 mice in each time point per group);HE staining was used to observe the microvascular morphology and density changes;immune-fluorescence staining was used to visualize the differential expressions of factor Ⅷ related antigen (vWF) and zonulaoccludens-1 (ZO-1).Results Micro-vascular disorders began to appear from the first day of irradiation,deteriorating with time extension gradually.After the X-ray irradiation exposure,the protein expressions of vWF and ZO-1 in the irradiation group were significantly decreased as compared with those in the control group 1,7,30,90 and 180 days after irradiation (vWF:23.17±2.93 vs 15.80±2.39,21.25±2.33 vs 11.60±2.3,19.78±2.16 vs 8.20±1.64,17.21±3.31 vs 6.00±2.12 and 16.98±1.92 vs 3.80±2.59;ZO1:26.17±3.31 vs 15.40±1.82,23.20±2.93 vs 12.00±1.58,20.88±2.20 vs 9.10±2.55,18.32±1.87 vs 6.20±1.92 and 17.50±1.91 vs 2.40±1.52,P<0.05);besides,the decreased expression ofvWF and ZO-1 in the irradiation group showed a time-depended manner,with significant differences between each two time points (P<0.05).Conclusion X-rays may induce persistent micro-vascular injury and destroyed BBB tight junctions,which may be closely related to the occurrence and development of RBI.
6.Research progress of artificial intelligence convolutional neural network in whole slide image analysis
ZHAO Mengmeng ; WANG Yang ; DENG Jiajun ; SHE Yunlang ; CHEN Chang
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2019;26(11):1063-1068
Histopathology is still the golden standard for the diagnosis of clinical diseases. Whole slide image (WSI) can make up for the shortcomings of traditional glass slices, such as easy damage, difficult retrieval and poor diagnostic repeatability, but it also brings huge workload. Artificial intelligence (AI) assisted pathologist's WSI analysis can solve the problem of low efficiency and improve the consistency of diagnosis. Among them, the convolution neural network (CNN) algorithm is the most widely used. This article aims to review the reported application of CNN in WSI image analysis, summarizes the development trend of CNN in the field of pathology and makes a prospect.
7. Genomic sequence analysis of a hantavirus found in Yunnan bat
Hongyan DENG ; Jinglin WANG ; Lili LI ; Yunyun XIN ; Mengmeng LIU ; Yun WANG ; Zhaojun DUAN
Chinese Journal of Experimental and Clinical Virology 2018;32(2):140-144
Objective:
To understand the novel bat-borne hantavirus on Yunnan province.
Methods:
Eighty-four bats were collected from Puer, Yunnan from July to August in 2016. A hantavirus, named as DodeHV, was identified in Pomona Roundleaf Bat by high-throughput sequencing technology. Nested or Semi-nested reverse transcription-polymerase chain reaction was used to confirm and screen DodeHV, as well as to amplify its genome sequence by specific primers. Then homology and phylogenetic analysis of all three segments were conducted by using software MegAlign and MEGA 6.0.
Results:
All the positive individuals are Pomona Roundleaf bats by PCR in this study and 4 out of 67 (5.97%) Pomona Roundleaf bats were positive. The complete ORF of DodeHV S Segment, the most sequence of M and the complete sequence of L segment were obtained. It shared the highest homology with the strain XSV-VN1982B4 found on Phu Tho Province, Viet- Nam in 2013, the nucleotide sequence identities of S, M, L segment compared with XSV was 79.0%, 79.2%, 79.9% respectively, and its amino acid sequence identities was 93.4%, 94.8%, 96.6% respectively. Meanwhile, phylogenetic analysis showed that DodeHV was also closely related to strain XSV-VN1982B4.
Conclusions
The discovery of DodeHV enriched the virus reservoir of our country which is meaningful to public health. It is indicated that there is potential risk of bat-borne DodeHV at cross-border infection at frontier.
8.Targeting STAT3 alleviates peritoneal fibrosis by regulating glycolysis and mesothelial-mesenchymal transition
Qilei Deng ; Jiao Fu ; Nan Li ; Mengmeng He ; Dake Huang ; Pei Zhang
Acta Universitatis Medicinalis Anhui 2024;59(4):647-653
Objective :
To study the effect and mechanism of high glucose on mesothelial-mesenchymal transition (MMT) of peritoneal mesothelial cells (HMrSV5) , and the protective effect of pharmacological blocking of signal transducer and activator of transcription 3 (STAT3) on rat peritoneal fibrosis (PF) model .
Methods :
The animals were divided into three groups : the sham group , the model group , and the STAT3 inhibitor group . A miniature per- itoneal dialysis catheter was implanted under the dorsal skin of rat and the rat peritoneal fibrosis model was induced by daily injection of high glucose dialysate . After 10 weeks , HE staining was used to evaluate the histology of the peritoneum , and the level of transforming growth factor-β1 (TGF-β1) in the peritoneum was measured by immuno- histochemistry . HMrSV5 was cultured in high glucose and the optimal stimulation concentration of high glucose was determined by Western blot. High glucose was used to stimulate HMrSV5 after successful transfection with si - STAT3 and Western blot was used to measure the protein level of STAT3 , p-STAT3 , and the key enzymes of glycol- ysis 6-phosphofructo-2-kinase/fructose-2 , 6-biphosphatase 3 (PFKFB3) and lactate dehydrogenase A (LDHA) .
Results :
HE staining showed that administration of STAT3 inhibitor ( BP-1-102) could inhibit the thickening of subperitoneal tissue and the proliferation of vessels in HG dialysis rats . The expression of TGF-β1 in the rats perito- neum of the model group was significantly higher than that in the sham group , and the level of TGF-β1 was marked- ly lower in the STAT3 inhibitor group compared to the model group (P < 0. 05) . Compared to the control group , high glucose induced the up-regulation of α-smooth muscle actin ( α-SMA) , the down-regulation of E-cadherin and STAT3 activation in HMrSV5 (P < 0. 05) . Mesothelial cells treated with high glucose also exhibited high expres- sion of the key enzymes of glycolysis ( PFKFB3 , LDHA) ( P < 0. 05) , and si-STAT3 can effectively inhibit the overexpression of PFKFB3 and LDHA induced by high glucose ( P < 0. 05) .
Conclusion
STAT3 is involved in high glucose-induced HMrSV5 hyperglycolysis and MMT , and targeting STAT3 alleviates peritoneal fibrosis and an- giogenesis during peritoneal dialysis treatment in rats .
9.Application value of radiomics-based machine learning model in identifying the degree of pulmonary ground-glass nodule infiltration
Hua HE ; Delun YANG ; Shuo SUN ; Li HE ; Xiang MA ; Mengmeng ZHAO ; Jiajun DENG ; Minjie MA ; Biao HAN ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2023;30(04):522-531
Objective To establish a machine learning model based on computed tomography (CT) radiomics for preoperatively predicting invasive degree of lung ground-glass nodules (GGNs). Methods We retrospectively analyzed the clinical data of GGNs patients whose solid component less than 3 cm in the Department of Thoracic Surgery of Shanghai Pulmonary Hospital from March 2021 to July 2021 and the First Hospital of Lanzhou University from January 2019 to May 2022. The lesions were divided into pre-invasiveness and invasiveness according to postoperative pathological results, and the patients were randomly divided into a training set and a test set in a ratio of 7∶3. Radiomic features (1 317) were extracted from CT images of each patient, the max-relevance and min-redundancy (mRMR) was used to screen the top 100 features with the most relevant categories, least absolute shrinkage and selection operator (LASSO) was used to select radiomic features, and the support vector machine (SVM) classifier was used to establish the prediction model. We calculated the area under the curve (AUC), sensitivity, specificity, accuracy, negative predictive value, positive predictive value to evaluate the performance of the model, drawing calibration and decision curves of the prediction model to evaluate the accuracy and clinical benefit of the model, analyzed the performance in the training set and subgroups with different nodule diameters, and compared the prediction performance of this model with Mayo and Brock models. Two primary thoracic surgeons were required to evaluate the invasiveness of GGNs to investigate the clinical utility of the mode. Results A total of 400 patients were divided into the training set (n=280) and the test set (n=120) according to the admission criteria. There were 267 females and 133 males with an ……
10.Fucoidan-functionalized activated platelet-hitchhiking micelles simultaneously track tumor cells and remodel the immunosuppressive microenvironment for efficient metastatic cancer treatment.
Rong GUO ; Miao DENG ; Xuan HE ; Mengmeng LI ; Jiaxin LI ; Penghui HE ; Houqin LIU ; Man LI ; Zhirong ZHANG ; Qin HE
Acta Pharmaceutica Sinica B 2022;12(1):467-482
Tumor metastasis is responsible for most mortality in cancer patients, and remains a challenge in clinical cancer treatment. Platelets can be recruited and activated by tumor cells, then adhere to circulating tumor cells (CTCs) and assist tumor cells extravasate in distant organs. Therefore, nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor, CTCs and metastasis in distant organs. However, the activated tumor-homing platelets will release transforming growth factor-β (TGF-β), which promotes tumor metastasis and forms immunosuppressive microenvironment. Therefore, a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals. In this study, a fucoidan-functionalized micelle (FD/DOX) was constructed, which could efficiently adhere to activated platelets through P-selectin. Compared with the micelle without P-selectin targeting effect, FD/DOX had increased distribution in both tumor tissue and metastasis niche, and exhibited excellent anti-tumor and anti-metastasis efficacy on 4T1 spontaneous metastasis model. In addition, due to the contribution of fucoidan, FD/DOX treatment was confirmed to inhibit the expression of TGF-β, thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment. The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.