1.Mechanism of Shengmai Injection Against Cerebral Ischemia Based on Proteomics
Jingtong LIU ; Shaowei HU ; Mengli CHANG ; Jing XU ; Qingqing CAI ; Xinghong LI ; Liying TANG ; Huanhuan WANG ; Hongwei WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):57-67
ObjectiveTo evaluate pharmacological effects of Shengmai injection(SMI)on cerebral ischemia and study its neuroprotective mechanism. MethodsMale specific pathogen-free (SPF) Sprague-Dawley (SD) rats were randomly divided into a sham group, a model group, a low-dose SMI group(3 mL·kg-1), a middle-dose SMI group(6 mL·kg-1), a high-dose SMI group(12 mL·kg-1), and a Ginaton group(4 mL·kg-1)according to the random number table method, with 12 rats in each group. The rat model of cerebral ischemia-reperfusion(MCAO/R)was prepared via the suture method. The administration groups were intraperitoneally injected with corresponding concentrations of SMI or Ginaton injection after reperfusion, which was conducted for 3 consecutive days. The sham group and model group were administered the equivalent volume of physiological saline. The pharmacological effects of SMI on brain injury in MCAO/R rats were evaluated by neurological function scores, cerebral infarction area, hematoxylin-eosin (HE) staining, Nissl staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Western blot. The dominant link and key protein of SMI treating cerebral injury were explored using proteomic analysis. The related mechanisms of SMI were further validated using enzyme-linked immunosorbent assay (ELISA), Western blot, and chloride ion fluorescence probe with oxygen-glucose deprivation/reoxygenation(OGD/R)-treated PC12 cells and MCAO/R rats. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly decreased density of Nissl bodies and neurons(P<0.01). Compared with the model group, the SMI groups exhibited significantly decreased neurological function scores, cerebral infarction area, neuronal apoptosis rate, and expression levels of apoptosis related proteins (P<0.05, P<0.01)and significantly increased density of Nissl bodies and neurons (P<0.05). The proteomic analysis results showed that oxidative stress and inflammatory response were important processes of SMI intervening in MCAO/R injury, and the chloride intracellular channel protein 1 (CLIC1) was one of key proteins in its action network. The levels of representative indicators of oxidative stress and inflammatory response in the MCAO/R rats of the SMI groups were significantly reduced, compared with those in the model group(P<0.05, P<0.01), and the expression levels of CLIC1 and downstream NOD-like receptor protein 3 (NLRP3) decreased (P<0.01). In addition, the experimental results based on the OGD/R PC12 cells showed that SMI significantly increased the cell survival rate(P<0.01) and significantly decreased the intracellular chloride ion concentration(P<0.05). ConclusionSMI has neuroprotective effects. Oxidative stress and inflammatory response are key processes of SMI intervening in MCAO/R injury. The potential mechanism is closely related to the regulation of CLIC1.
2.Effects of sinomenine on LPS-induced apoptosis and autophagy of lung epithelial cells in JNK/c-Jun signaling pathway
Li LI ; Yingying SUN ; Ying BAI ; Luowen HU ; Qingqing WEI ; Yupeng YAN ; Ji WANG
Chinese Journal of Immunology 2024;40(4):731-735
Objective:To explore the effect of sinomenine(SIN)on LPS-induced apoptosis and autophagy of lung epithelial cells through the JNK/c-Jun signaling pathway.Methods:MLE-12 lung epithelial cells were cultured,and the toxicity of SIN was detected by CCK-8.Apoptosis was detected by flow cytometry,the number of autophagosomes was detected by immunofluorescence,and the expression levels of apoptosis,autophagy and JNK/c-Jun signaling pathway-related proteins were detected by Western blot.Results:After LPS modeling,apoptosis rate and the number of autophagosomes were increased,the protein levels of Cleaved caspase-3,Bax,and Beclin-1,and LC3Ⅱ/LC3Ⅰ,p-JNK/JNK and p-c-Jun/c-Jun were increased(P<0.05);Bcl-2 and P62 protein levels were decreased(P<0.05).SIN treatment can significantly improve the effects of LPS on apoptosis and autophagy,as well as the regulation of the JNK/c-Jun signaling pathway(P<0.05).Treatment with the autophagy inhibitor 3-MA or the JNK agonist ANISO could partially reverse the protective effect of SIN on LPS-induced lung epithelial cells(P<0.05).Conclusion:SIN may increase autophagy and pro-tect lung epithelial cells damaged by LPS by regulating proteins related to the JNK/c-Jun signaling pathway.
3.Enhanced CT radiomics-CT feature model for differentiating sinonasal squamous cell carcinoma and lymphoma
Haijing CHEN ; Yaying YANG ; Wei ZHAO ; Bo HE ; Li WU ; Jihong HU ; Qingqing LI
Chinese Journal of Medical Imaging Technology 2024;40(7):1003-1008
Objective To investigate the value of enhanced CT radiomics combined with CT features model(combined model)for differentiating squamous cell carcinoma(SNSCC)and sinonasal lymphoma(SL).Methods Totally 68 patients with SNSCC and 63 patients with SL were retrospectively collected and divided into training set(n=92,including 48 SNSCC and 44 SL)and verification set(n=39,including 20 SNSCC and 19 SL)at the ratio of 7:3.Univariate analysis and logistic regression were used to analyze clinical data and CT manifestations in training set,and the independent predictive factors for differentiating SNSCC and SL were screened and used to construct a CT features model.Based on enhanced venous phase CT of training set,the best radiomics features of lesions were extracted and screened.The radiomics model was then established,and the radiomics label was calculated.The combined model was finally constructed based on CT model and radiomics labels,and its nomogram was drawn.Receiver operating characteristic(ROC)curve were drawn,and the areas under the curve(AUC)were calculated to evaluate the efficacy of each model for differentiating SNSCC and SL.Calibration and decision curve analysis were used to evaluate the calibration efficacy and clinical benefit of the obtained combined model.Results The primary location of the lesion and bone invasion showed on CT were both independent predictive factors for SNSCC and SL(both P<0.05),and CT model was constructed.Based on enhanced venous phase CT,3 best radiomics features were selected to establish the radiomics model.The AUC of CT,radiomics and combined model in training set was 0.895,0.730 and 0.925,respectively,and significant differences of AUC were found among 3 models(Z=-3.964 to-1.833,all P<0.05).The AUC of CT,radiomics and combined model in verification set was 0.845,0.684 and 0.868,respectively,of combined model was greater than of radiomics model(Z=-2.568,P=0.010).The combined model had good calibration.Taken 15%-62% and 85%-92% as the thresholds in training set and 88% to 95% in validation set,the clinical net benefit of combined model was high.Conclusion The obtained enhanced CT radiomics combined with CT features model could be used to effectively differentiate SNSCC and SL.
4.Preoperative Prediction of Sentinel Lymph Node of Breast Cancer Based on MRI
Yijie SHI ; Qingqing CHEN ; Jie HE ; Hongjie HU
Chinese Journal of Medical Imaging 2024;32(10):1021-1026
Purpose To investigate the value of MRI multimodal parameters in predicting sentinel lymph node(SLN)metastasis of breast cancer,and to develop an effective prediction model to reduce the unnecessary biopsy rate of SLN.Materials and Methods Preoperative MRI data of 310 patients with cN0 breast cancer confirmed by operation and pathology in Sir Run Run Shaw Hospital,Zhejiang University School of Medicine from January 2019 to December 2021 were retrospectively analyzed,and all patients were divided into positive group and negative group according to whether SLN metastasized.Imaging features of breast lesions were evaluated independently by two radiologists,differences in parameter between the two groups were compared,independent predictors were screened to build models and evaluate diagnostic efficacy.Results The breast lesions in SLN positive group were located in the upper quadrant(χ2=14.94),non-single(χ2=9.29),circular enhancement(χ2=9.23)and the positive rate of adjacent angiogenesis(χ2=9.91)were higher than those in SLN negative group.The lesions in SLN positive group were larger(Z=-2.97,-2.73),and the early enhancement rate was higher(t=-3.48).The minimum apparent diffusion coefficient and relative apparent diffusion coefficient(minimum apparent diffusion coefficient of lesions/apparent diffusion coefficient of glands,rADC)were lower(Z=-7.33,-10.74),all P<0.05.Logistic regression results showed lesion location(OR=4.17,95%CI 1.86-9.35,P=0.001),early enhancement rate(OR=1.01,95%CI 1.00-1.02,P=0.019)and rADC(OR=54.67,95%CI 23.72-126.02,P<0.001)were independent risk factors for SLN metastasis.The model combining lesion location and rADC had the best predictive performance,with a negative predictive value of 96.5%and a 46.1%reduction in unnecessary biopsies.Conclusion SLN preoperative prediction model(lesion location,rADC)based on conventional MRI characteristic parameters has reliable negative prediction value,which is expected to reduce the unnecessary biopsy of nearly half of the patients with stage cN0 breast cancer.
5.Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fracture with kyphotic deformity in the elderly (version 2024)
Jian CHEN ; Qingqing LI ; Jun GU ; Zhiyi HU ; Shujie ZHAO ; Zhenfei HUANG ; Tao JIANG ; Wei ZHOU ; Xiaojian CAO ; Yongxin REN ; Weihua CAI ; Lipeng YU ; Tao SUI ; Qian WANG ; Pengyu TANG ; Mengyuan WU ; Weihu MA ; Xuhua LU ; Hongjian LIU ; Zhongmin ZHANG ; Xiaozhong ZHOU ; Baorong HE ; Kainan LI ; Tengbo YU ; Xiaodong GUO ; Yongxiang WANG ; Yong HAI ; Jiangang SHI ; Baoshan XU ; Weishi LI ; Jinglong YAN ; Guangzhi NING ; Yongfei GUO ; Zhijun QIAO ; Feng ZHANG ; Fubing WANG ; Fuyang CHEN ; Yan JIA ; Xiaohua ZHOU ; Yuhui PENG ; Jin FAN ; Guoyong YIN
Chinese Journal of Trauma 2024;40(11):961-973
The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.
6.Screening of active components of Polygonum orientale flower against myocardial ischemia-reperfusion injury in rats under physiological and pathological states
Shasha REN ; Jianchun HU ; Yuanxian ZHANG ; Qingqing CHEN ; Chunhua LIU ; Lin ZHENG ; Zipeng GONG ; Yong HUANG ; Yang JIN ; Yueting LI
China Pharmacy 2024;35(16):1957-1963
OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury (MIRI) in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group, normal administration group, MIRI control group and MIRI administration group, with 5 rats in each group. After drug intervention or modeling and drug intervention, chromatographic separation plasma samples were collected, and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps, the maps of each plasma sample, and the relevant literature. At the same time, the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis, the differential transitional components were screened out according to the value of variable importance in the projection (VIP)>1, to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group, MIRI group, positive control group (Compound danshen tablets 0.2 g/kg, 3 times a day), and potentially active compound groups (10 mg/kg, twice a day), with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically, for 3 consecutive days. The activity of superoxide dismutase (SOD), the leakages of lactate dehydrogenase (LDH), creatine kinase isoenzyme-MB (CK-MB) and cardiac troponin Ⅰ (cTnⅠ) in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower, and 14 of them were determined, including gallic acid, catechin, protocatechuic acid and so on. There were fifteen (including 6 absorbed prototype components and 9 metabolites) and nineteen transitional components (including 6 absorbed prototype components and 13 metabolites) in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats, and the VIP values of kaempferol glucuronidation metabolites, quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group, the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group (P<0.01), and the leakages of LDH, CK-MB, and cTnⅠ in the plasma of MIRI rats were reduced significantly (P<0.01). CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine, quercetin, kaempferol and kaempferol-3-O-β-D-glucoside.
7.Contrast-enhanced CT and MRI in differentiating squamous cell carcinoma of the nasal cavity and sinuses from lymphoma
Haijing CHEN ; Yaying YANG ; Wei ZHAO ; Jihong HU ; Li WU ; Linglin ZHENG ; Yan WU ; Qingqing LI
The Journal of Practical Medicine 2024;40(3):394-399
Objective To investigate the enhanced CT and MRI imaging features of nasal sinus squamous cell carcinoma(SCC)and lymphoma(NHL),and to analyze the efficacy of different imaging features in differentiating nasal sinus SCC from NHL.Methods The imaging,clinical and pathological data of 67 patients with sinus SCC and NHL who underwent sinus CT and MRI with contrast CT and MRI in our hospital and confirmed by surgical pathology were retrospectively analyzed,and the tumor origin,maximum diameter,CT density,MRI signal intensity,enhancement degree,tumor internal necrosis,adjacent bone destruction,invasion of surrounding tissues,and The imaging features such as cervical lymph node metastasis within the scanning range were analyzed,and the receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to analyze the efficacy of different imaging features to distinguish nasal sinus SCC and NHL.Results There were statistically significant differences between the five imaging features of nasal sinus SCC and NHL,including tumor origin,maximum diameter,internal tumor necrosis,surrounding bone destruction and peripheral tissue invasion(P<0.05),and the AUC of differentiating SCC and NHL were 0.708,0.694,0.785,0.850 and 0.629,respectively.The AUC of SCC and NHL was 0.969,and the sensitivity and specificity were 83.9%and 97.2%,respectively.Conclusion On contrast-enhanced CT and MRI,the imaging signs of tumor origin,maximum diameter,tumor internal necrosis,bone destruction and surrounding tissue invasion are helpful to distinguish nasal sinus SCC from NHL,especially if the tumor originates in the nasal cavity,necrosis is rare,bone destruction is mild,and the possibility of nasal sinus NHL should be given priority.Contrast-enhanced CT and MRI can help differentiate nasal sinus SCC from NHL,and the combination can help improve differential diagnostic performance.
8.Preoperative Prediction of Lymphovascular Invasion of Node-Negative Gastric Cancer Based on CT Radiomics
Feifei LOU ; Qingqing CHEN ; Hao HUANG ; Fang WANG ; Jie HE ; Enhui XIN ; Hongjie HU
Chinese Journal of Medical Imaging 2024;32(1):73-80
Purpose To explore the value of CT-based radiomics in the preoperative prediction of lymphatic invasion of node-negative gastric cancer,and to construct a nomogram combined with clinical variables.Materials and Methods The clinical and CT imaging data of 173 gastric cancer patients with lymph node negative and pathologically confirmed gastric cancer in the Sir Run Run Shaw Hospital from January 2019 to June 2021 were retrospectively analyzed.A total of 60 cases with lymphovascular invasion(LVI)positive patients and 113 cases with LVI negative patients were included,and randomly divided into train cohort(n=121)and test cohort(n=52)at 7∶3.Based on the train cohort,the clinical model,the radiomics model,the fusion model were constructed and verified in the test cohort.Clinical data and conventional CT features included age,gender,tumor marker,tumor location,tumor morphology,enhancement range,etc.The clinical significant variables were selected through univariate and multivariate analysis to establish the clinical model.The tumor regions of interest were segmented and radiomics features were extracted by using the 3D-Slicer software.Key features were screened through least absolute shrinkage and selection operator regression analysis,and then the radiomics model was constructed with random forest algorithm,and converted to random forest score(RF score).The fusion model was constructed via combining clinical significant variables and RF score,and visualized as a nomogram.The receiver operator characteristic curve and area under curve(AUC)were used to evaluate the prediction performance of the models.Decision curve analysis was used to calculate the clinical practicability.Results The radiomics model was superior to the clinical model.The radiomics model AUC of the train cohort and the test cohort were 0.872(0.810 to 0.935)and 0.827(0.707 to 0.947),the clinical model AUC were 0.767(0.682 to 0.852)and 0.761(0.610 to 0.913).The nomogram further improved the predictive efficiency,the AUC in train cohort and test cohort reached 0.898(0.842 to 0.953)and 0.844(0.717 to 0.971),respectively.Decision curve analysis demonstrated clinical benefits of nomogram.Conclusion The radiomics model can be used to preoperatively predict LVI of node-negative gastric cancer.The nomogram can further improve the prediction efficiency.
9.Metabolomics Analysis of Tupaia belangeri Breast Tumor Model
Xi FANG ; Qingqing AO ; Chunhong LI ; Yiqiang OUYANG ; Songchao GUO ; Bing HU
Laboratory Animal and Comparative Medicine 2024;44(1):52-61
ObjectiveTo explore the metabolic changes during the development of Tupaia belangeri breast tumors, to investigate the close relationship between the changes of serum metabolic substances and the occurrence and progression of tumors, and to screen for biomarkers reflecting the progression of breast tumors. MethodsBreast tumors in Tupaia belangeri were induced by orally administering 7,12-dimethylbenzoanthracene (DMBA) three times, with a 15-day interval between each administration, along with a high-fat and high-sugar diet. The DMBA-induced breast cancer group and the DMBA-inducedwithout breast cancer group were compared with the control group. Untargeted determination of serum metabolites was performed using gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) in DMBA-induced Tupaia belangeri with breast cancer, DMBA-induced without breast cancer and the control group. Multidimensional statistical analysis including unsupervised principal component analysis (PCA), and orthogonal partial least squares analysis (OPLS-DA) were conducted. Furthermore, t-test was used for intergroup differential comparison. Differential metabolites were screened under VIP>1 and P<0.05 conditions, and significantly changing differential metabolites were identified using the HMDB online database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database was utilized to enrich metabolic-related gene regulatory pathways. ResultsThe incidence of breast tumors was 40% in DMBA-induced Tupaia belangeri. Compared with the control group, 30 metabolic differential products were detected in the serum of the group with breast cancer, with 18 down-regulated and 12 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in four metabolic pathways: glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism. Compared with the group without breast cancer, 18 metabolic differential products were detected, with 7 down-regulated and 11 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in the citric acid cycle and glutamate metabolism. Compared with the control group, 31 metabolic differential products were detected in the serum of the groups without breast cancer, with 14 down-regulated and 17 up-regulated (VIP>1, P<0.05). KEGG pathway analysis revealed significant changes in three metabolic pathways: glutamate metabolism, glyceride metabolism, and citric acid cycle. ConclusionMetabolomics analysis can reveal the characteristics of changes in metabolites in the serum of breast tumors. The results suggest that glutamate metabolism, glyceride metabolism, citric acid cycle, and alanine metabolism pathways are associated with the occurrence and development of DMBA-induced breast tumors in Tupaia belangeri. It provides a foundation for further research into the biological mechanism of breast cancer.
10.Effects of retinopathy on visual function in type 2 diabetes mellitus
Tianlin ZHANG ; Zongli HU ; Huiqun WANG ; Fouxi ZHAO ; Qiying PAN ; Qingqing ZHAN ; Qinyu AN ; Fuyan ZHANG ; Tao LIU ; Yuandong HU
Chinese Journal of Preventive Medicine 2024;58(9):1331-1340
Objective:To study the influence of the severity of diabetic retinopathy (DR) on the visual function of patients with type 2 diabetes, to provide scientific basis for the early prevention and control of DR.Methods:This study was designed as a cross-sectional study, recruiting already-diagnosed type 2 diabetes patients in four community health service centers in Guizhou Province between February and September 2022. Employing the Chinese version of the Visual Function Index-14 (VF-14), assess the participants′ near vision, visual adaptation, subjective visual perception, and stereo vision, with higher scores indicating poorer visual function. Categorize the severity of each eye′s damage into no diabetic retinopathy (DR), mild non-proliferative diabetic retinopathy (NPDR), moderate NPDR, severe NPDR, and proliferative diabetic retinopathy (PDR), and use a 5-level DR grading system to evaluate the overall severity of diabetic retinopathy in both eyes. Employing linear regression analysis to investigate the linear relationship between DR and visual function index. Local weighted regression evaluates the nonlinear relationship between the DR composite score and the scores of visual function, with a steeper slope indicating poorer visual function for that level.Results:A total of 542 patients with type 2 diabetes were investigated, including 244 (45.02%) males, 298 (54.98%) females, and 162 (29.89%) patients with DR. After adjusting for confounders, compared with those without DR, patients with binocular DR Had overall scores ( β=0.136, P=0.003), near vision ( β=0.163, P<0.001), visual adaptation ( β=0.092, P=0.042), subjective vision ( β=0.120, P=0.009) and stereo vision ( β=0.094, P=0.044) were higher than those without DR. There were no differences in visual functions between DR And monocular DR. The local weighted regression curve showed that near vision (slope: 23.78) and overall score (slope: 58.37) increased sharply from mild to moderate NPDR in both eyes. Visual adaptation (slope: 5.37, 7.72), subjective vision (slope: 6.53, 7.93), stereovision (slope: 0.74, 0.91) increased slowly in mild to moderate NPDR in both eyes and in moderate to severe NPDR/PDR in both eyes. Conclusion:Binocular DR is associated with impaired visual function, but there is no difference between monocular DR And non-DR visual function. The early damage of DR To visual function is mainly manifested in near vision. In the prevention and control of DR, more attention should be paid to visual function, especially the change of near vision, and retinal damage should not be assessed solely by visual status.

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