1. Analysis and verification of the effect of Yi Qi Yang Yin decoction on rheumatoid arthritis
Rui GUAN ; Jiashu YAO ; Yeyu ZHAO ; Jiannan ZHENG ; Qing QI ; Jing YU ; Mingli GAO
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(1):26-36
AIM: Yi Qi Yang Yin Decoction (YQYY) has been used to treat patients with rheumatoid arthritis (RA) and achieved good results in clinical applications, but the mechanism still needs to be explored. The purpose was to investigate the mechanism of YQYY in rats with collagen-induced arthritis. METHODS: The possible treatment target and signaling pathway were predicted by bioinformatics and network pharmacology analysis. Elisa,quantitative real-time polymerase chain reaction, and Western Blot were used to verify the mechanism of YQYY in treating RA. RESULTS: FABP4, MMP9 and PTGS2 were the most common predicational therapeutic targets. The results of pathology and CT showed that YQYY could improve ankle swelling, synovitis and bone erosion in CIA rats. Compared with the model group, YQYY or YQYY+MTX can significantly reduce the secretion of CRP, TNF-α, IL-1β and FABP4 in serum of CIA rats (P<0.05 or P<0.01), meanwhile, reduce the mRNA of FABP4, IKKα and p65 in synovial tissue (P<0.01), PPARγ was increased (P<0.01). YQYY could significantly reduce the expression of FABP4, IKKα and pp65 proteins in synovium, and suppress the activate of NF - κB signaling pathway. CONCLUSION: FABP4, MMP9 and PTGS2 may be the targets of YQYY decoction for RA treatment. YQYY can relieve joint symptoms in CIA rats, and regulate inflammation by inhibiting FABP4 / PPARγ/NF - κB signaling pathway, playing a role in the treatment of RA. The effect of YQYY combined with MTX was more prominent. This provided experimental evidence for the efficacy of YQYY decoction in clinical practice.
2.Value of left ventricular shape index and eccentricity index of gated myocardial perfusion imaging in the evaluation of left ventricular remodeling in patients with myocardial infarction
Xiaoyi XI ; Luxia WANG ; Qi YAO ; Shihao HUANGFU ; Yuxin XIAO ; Zhifang WU ; Ping WU ; Li LI ; Rui YAN ; Yuetao WANG ; Minfu YANG ; Sijin LI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(1):6-11
Objective:To investigate the clinical value of left ventricular shape index (SI) and eccentricity index (EI) in evaluating left ventricular remodeling.Methods:A retrospective analysis was performed on 324 patients (264 males, 60 females, age (62.5±11.8) years) diagnosed with myocardial infarction (MI) and 113 healthy controls (HC; 47 males, 66 females, age (57.8±10.7) years) who received gated myocardial perfusion imaging (GMPI) in First Hospital of Shanxi Medical University from January 2016 to September 2020. SI (end-diastolic SI (EDSI), end-systolic SI (ESSI)), EI and left ventricular function parameters (end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular ejection fraction (LVEF), summed motion score (SMS), summed thickening score (STS), peak ejection rate (PER) and peak filling rate (PFR)) were obtained by quantitative gated SPECT (QGS) software. Propensity score (PS) inverse probability of treatment weighting (IPTW) was used to balance the intergroup covariates. The differences and correlations of EDSI, ESSI, EI and left ventricular function parameters between patients in MI group and HC group were analyzed. ROC curve analysis was used to evaluate the values of EDV, EDSI, ESSI and EI alone and in combination in the assessment of left ventricular systolic function impairment. Data were analyzed by independent-sample t test, Pearson correlation and Spearman rank correlation analyses, and Delong test. Results:After IPTW, EDSI and ESSI in MI group ( n=319) were higher than those in HC group ( n=133; EDSI: 0.66±0.09 vs 0.60±0.06; ESSI: 0.59±0.11 vs 0.47±0.07; t values: 8.05, 14.67, both P<0.001), and EI was lower than that in HC group (0.81±0.06 vs 0.85±0.03; t=-8.93, P<0.001). In both groups, there were significant correlations between EDSI and ESSI ( r values: 0.928, 0.873), between EDSI, ESSI and EI ( r values: from -0.831 to -0.641), between EDSI, ESSI and LVEF ( r values: from -0.627 to -0.201), between ESSI and EDV, ESV and SMS ( rs values: 0.336-0.584), between ESSI and -PER, PFR ( rs values: from -0.406 to -0.402, r values: from -0.352 to -0.325) (all P<0.01). ROC curve analysis showed that EDV (AUC: 0.895) and ESSI (AUC: 0.839) had the highest efficacy in evaluating left ventricular systolic function impairment in MI group and HC group, respectively. EDV-EDSI-ESSI-(1-EI) had higher efficacy in the assessment of impaired left ventricular systolic function in MI group (AUC: 0.956), which was higher than that of EDV or EDV-EDSI or EDV-ESSI or EDV-(1-EI) ( z values: from -2.64 to -2.18, P values: 0.008-0.029); EDV-EDSI-ESSI-(1-EI) also had high efficacy in HC group (AUC: 0.911), which was higher than that of EDV or EDV-EDSI or EDV-(1-EI) ( z values: from -2.60 to -2.43, P values: 0.009-0.015). Conclusions:In MI patients, the increase of SI and the decrease of EI indicate the increase of left ventricular sphericity and the aggravation of left ventricular remodeling. SI and EI have certain clinical application values in evaluating left ventricular morphology, predicting left ventricular remodeling and left ventricular systolic function impairment.
3.Pathologic Function of Cyclin-dependent Kinase 5 and Its Relationship With Exercise
Dan JIN ; Rui-Qi HUANG ; Ting-Ting YAO ; Xue-Jie YI ; Hai-Ning GAO
Progress in Biochemistry and Biophysics 2024;51(11):2868-2879
Cyclin-dependent kinases (CDKs) are proline-induced serine/threonine kinases that are primarily involved in the regulation of cell cycle, gene transcription, and cell differentiation. In general, CDKs are activated by binding to specific regulatory subunits of cell cycle proteins and are regulated by phosphorylation of specific T-loops by CDK activated kinases. In the CDKs family, cyclin-dependent kinase 5 (CDK5) is a specialized member whose activity is triggered only by interaction with p35 and p39, which do not have the same sequence as the cell cycle proteins, and this may be one reason why CDK5 is distinguished from other CDK members by its structural and functional differences. In addition, unlike most CDK members that require phosphorylation at specific sites to function, CDK5 does not require such phosphorylation, and it can be activated simply by binding to p35 and p39. More notably, inhibitors that are commonly used to inhibit the activity of other CDK members have almost zero effect on CDK5. In contrast, CDK5, as a unique CDK family member, plays an important role in the development of numerous diseases. In metabolic diseases, elevated CDK5 expression leads to decreased insulin secretion, increased foam cell formation and triggers decreased bone mass in the body, thus accelerating metabolic diseases, and the role of CDK5 in bone biology is gradually gaining attention, and the role of CDK5 in bone metabolic diseases may become a hotspot for research in the future; in neurodegenerative diseases, hyperphosphorylation of Tau protein is an important hallmark of Alzheimer’s disease development, and changes in CDK5 expression are associated with Tau protein phosphorylation and nerve death, indicating that CDK5 is highly related to the development of the nervous system; in tumor diseases, the role of CDK5 in the proliferation, differentiation and migration and invasion of tumor cells marks the development of tumorigenesis, but different researchers hold different views, and further studies are needed in the follow-up. Therefore, the study of its mechanism of action in diseases can help to reveal the pathogenesis and pathological process of diseases. Appropriate exercise not only helps in the prevention of diseases, but also plays a positive role in the treatment of diseases. Exercise-induced mechanical stress can improve bone microstructure and increase bone mass in osteoporosis patients. In addition, exercise can effectively inhibit neuronal apoptosis and improve mitochondrial dysfunction, more importantly, appropriate exercise can inhibit the proliferation of cancer cells to a certain extent. It can be seen that exercise occupies a pivotal position in the prevention and treatment of pathologic diseases. It has been shown that exercise can reduce the expression of CDK5 and affect the pathological process of neurological diseases. Currently, there is a dearth of research on the specific mechanisms of CDK5’s role in improving disease outcomes through exercise. In order to understand its effects more comprehensively, subsequent studies need to employ diverse exercise modalities, targeting patients with various types of diseases or corresponding animal models for in-depth exploration. This article focuses on the pathological functions of CDK5 and its relationship with exercise, with a view to providing new insights into the prevention and treatment of disease by CDK5.
4.Exploration on the Medication Rules of HUANG Li in Treating Recurrent Angina Pectoris After Percutaneous Coronary Intervention for Coronary Heart Disease
Shi-Yi TAO ; Xian-Wen TANG ; Lin-Tong YU ; De-Shuang YANG ; Rui-Qi YAO ; Lan-Xin ZHANG ; Jia-Yun WU ; Li HUANG
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(6):1598-1606
Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.
5.The mediating effect of perceived social support in the relationship between maternal personality traits and pregnancy-related anxiety.
Jia Shu ZHU ; Rui WANG ; Ye LI ; You Juan FU ; Hong Ya LIU ; Jia Qi LI ; Gui Xiang YAO ; Su Zhen GUAN
Chinese Journal of Preventive Medicine 2023;57(2):187-192
Objective: Exploring the mediating effect of perceived social support between the maternal personality traits and pregnancy-related anxiety. Methods: Singleton pregnant women who underwent antenatal checkups in the obstetrics department of general hospital affiliated to Ningxia Medical University from July to December 2021 were enrolled in this study to investigate perceived social support, pregnancy-related anxiety and conscious personality traits. Pearson correlation analysis was used to analyze the association between the maternal personality traits, perceived social support, and pregnancy-related anxiety, and the mediating effect of perceived social support was analyzed using Bootstrap method. Results: A total of 1 259 subjects were included in the study, of which 170 (13.50%) pregnant women felt introverted. The total score of perceived social support was (46.37±8.38), and 31.45% of pregnant women had high perceived social support. The total score of pregnancy-related anxiety was (21.48±5.53). The score of worry about fetal health was (10.09±3.24), and 368 (29.23%) of pregnant women had pregnancy-related anxiety. Maternal personality traits and pregnancy-related anxiety were negatively correlated (r=-0.076, P<0.05) and positively correlated with perceived social support during pregnancy (r= 0.127, P<0.05). Perceived social support during pregnancy and pregnancy-related anxiety were negatively correlated (r=-0.236, P<0.05). Perceived social support partially mediated the relationship between the maternal personality traits and pregnancy-related anxiety, with a relative effect value of 37.50%. Conclusion: The maternal personality traits, level of perceived social support and pregnancy-related anxiety are all related. Perceived social support could mediate the relationship between the maternal personality traits and pregnancy-related anxiety.
Female
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Pregnancy
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Humans
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Anxiety
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Pregnant Women
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Personality
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Social Support
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Prenatal Care
6.Clinical Effect of Bushen Shengxue Prescription on Chronic Aplastic Anemia and Its Effect on T Cell Subsets and Expression of T-bet and GATA3
Rui LI ; Yubin DING ; Wenru WANG ; Peizhen JIANG ; Jinhuan WANG ; Ruirong XU ; Shulian YANG ; Tao WANG ; Qifeng LIU ; Haixia WANG ; Antao SUN ; Jianping SHEN ; Yamei XU ; Jianying LI ; Yuhong YAO ; Xiaoqing DING ; Zhexin SHI ; Yongming ZHOU ; Qi HU ; Xiaohui SHEN ; Yonggang XU ; Feng LIU ; Rou MA ; Xudong TANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):94-101
ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells (T-bet) and GATA binding protein 3 (GATA3). MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective, double-blind and randomized control methods, the patients were randomized into three groups: kidney deficiency group, Qi and blood deficiency group, and control group. The three groups were respectively treated with Bushen Shengxue prescription granule, Yiqi Yangxue prescription granule, and Placebo (half the dose of Bushen Shengxue formula granules). In addition, all of them were given oral cyclosporin and androgen. The treatment lasted 6 months, with 3 months as a course. The blood routine indexes, T cell subsets, and fusion genes T-bet and GATA3 before and after treatment were analyzed, and the safety indexes were monitored. ResultDuring the observation, a total of 75 cases dropped out and 18 were rejected. Finally, 161 cases in the kidney deficiency group, 164 in the Qi and blood deficiency group, and 167 in the control group were included. After 6 months of treatment, the total effective rate was 98.8% (159/161) in the kidney deficiency group, which was higher than the 79.9% (131/164) in the Qi and blood deficiency group (χ2=30.135, P<0.01) and the 61.7% (103/167) in the control group (χ2=70.126, P<0.01). The total effective rate was higher in the Qi and blood deficiency group than in the control group (χ2=13.232, P<0.01). After treatment, the hemoglobin (HGB) content increased significantly in three groups (P<0.05) as compared with that before treatment, particularly the kidney deficiency group (P<0.01). After treatment, the white blood cell (WBC) count and platelet (PLT) count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group (P<0.01). There was no specific difference in neutrophils (ANC) after treatment among the three groups. At the same time point, the level of T helper type 1 (Th1) cells, Th1/Th2 ratio (P<0.05), level of CD4+, and CD4+/CD8+ ratio (P<0.05) were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19-, HLA/DR+, and CD25+ between the kidney deficiency group and the other two groups, but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group (P<0.05). ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism, inhibiting the activity of immune system, modulating T cell subsets, suppressing Th1 and CD4+, and promoting bone marrow hematopoiesis. Moreover, it is safe with little side effects, which is worthy of further promotion.
7.Impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease.
Ruo Nan WANG ; Ping WU ; Fei YAO ; Shi Hao HUANGFU ; Jun ZHANG ; Chu Xin ZHANG ; Li LI ; Hai Tao ZHOU ; Qi Ting SUN ; Rui YAN ; Zhi Fang WU ; Min Fu YANG ; Yue Tao WANG ; Si Jin LI
Chinese Journal of Cardiology 2022;50(11):1080-1086
Objective: This study sought to investigate the impact of different obesity patterns on coronary microvascular function in male patients with non-obstructive coronary artery disease. Methods: We retrospectively analyzed clinical data of male patients diagnosed with suspected coronary microvascular dysfunction (CMD) in the First Hospital of Shanxi Medical University between December 2015 and August 2021. All patients underwent the one-day rest and stress 13N-ammonia positron emission tomography myocardial perfusion imaging. Overall obesity was defined by body mass index (BMI) ≥28 kg/m2 and abdominal obesity was defined by waist circumference ≥90 cm. Hyperemic myocardial blood flow (MBF)<2.3 ml·min-1·g-1 or coronary flow reserve (CFR)<2.5 were referred as CMD. All patients were grouped based on their BMI and waist circumference. MBF, CFR, the incidence of CMD, hemodynamic parameters, and cardiac function were compared among the groups. Results: A total of 136 patients were included. According to BMI and waist circumference, patients were categorized into 3 groups: control group (n=45), simple abdominal obesity group (n=53) and compound obesity group (n=38). Resting MBF did not differ between groups (F=0.02,P=0.994). Compared with the control group, hyperemic MBF was significantly lower in the simple abdominal obesity and compound obesity groups ((2.82±0.64) ml·min-1·g-1, (2.44±0.85) ml·min-1·g-1 and (2.49±0.71) ml·min-1·g-1, both P<0.05, respectively). Hyperemic MBF was comparable among the groups of patients with obesity (P=0.772). CFR was significantly lower in the simle abdominal obesity group compared with the control group (2.87±0.99 vs. 3.32±0.62,P=0.012). Compared with the control group, CFR tended to be lower in the compound obesity group (3.02±0.91 vs. 3.32±0.62,P=0.117). The incidence of CMD was significantly higher in both the simple abdominal obesity and compound obesity groups than in the control group (62.3%, 52.6% vs. 22.2%, both P<0.01, respectively). Waist circumference was an independent risk factor for male CMD (OR=1.057, 95%CI: 1.013-1.103, P=0.011). Conclusions: In male patients with non-obstructive coronary artery disease, abdominal obesity is associated with decreased coronary microvascular function. Male patients with simple abdominal obesity face the highest risk of CMD.
Humans
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Male
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Coronary Artery Disease
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Coronary Circulation/physiology*
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Obesity, Abdominal
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Retrospective Studies
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Obesity/epidemiology*
;
Hyperemia
8.Risk assessment for noise-induced hearing loss in automotive assembly workers
Liang-liang GUO ; Jia-bing WU ; Kun WU ; Yong MEI ; Liang-ying MEI ; Rui-jie LING ; Cheng QI ; Jian-ru ZHENG ; Rong-bin SUN ; Liang-liang ZHU ; Wei-wei SHI ; Shao-hua YANG ; Jing CHEN ; Li YAO ; Yan-ping YAO ; Hong YIN ; Li-hua DING ; Xiao-juan WU
Journal of Public Health and Preventive Medicine 2022;33(6):63-67
Objective To evaluate the risk of hearing loss of assembly workers in an automobile manufacturing factory. Methods An 8-hour equivalent sound level monitoring was carried out for assembly posts in an automobile factory. The risk of noise-induced hearing loss of assembly workers was measured using the method specified in ISO 1999:2013(E). The risk of noise-induced hearing loss was assessed in a graded manner according to the Guidelines for the Management of Occupational Disease Hazards from Noise. The results were statistically analyzed using Pearson correlation analysis. Results The average 8-hour equivalent sound level of the assembly work post in this automobile manufacturing factory was 89.5 dB (A). At 4000 Hz, the hearing loss N50 (dB) of assembly workers reached the maximum. The longer the exposure time, the higher the risk of high-frequency standard hearing threshold shift. The risk of high-frequency standard hearing threshold shift was at a relatively high level at 30 years of work, while the risk of noise deafness reached a higher level after 40 years of work. Conclusion The 8-hour equivalent sound level (LEX,8h) of assembly workers in the automobile factory exceeds the occupational exposure limit. With the increase of exposure years, the risk of high-frequency standard hearing threshold shift and noise deafness increases.
9.Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure.
Shi Xu WANG ; Yan KE ; Yu Meng LIU ; Si Yao LIU ; Shi Bo SONG ; Shun HE ; Yue Ming ZHANG ; Li Zhou DOU ; Yong LIU ; Xu Dong LIU ; Hai Rui WU ; Fei Xiong SU ; Feng Ying ZHANG ; Wei ZHANG ; Gui Qi WANG
Chinese Journal of Oncology 2022;44(5):395-401
Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.
Artificial Intelligence
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Endoscopy/methods*
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Esophageal Neoplasms/pathology*
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Esophageal Squamous Cell Carcinoma/diagnostic imaging*
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Humans
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Narrow Band Imaging
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Precancerous Conditions/diagnostic imaging*
;
Sensitivity and Specificity
10.Therapeutic effects of alkaloids in Tibetan medicine Bangna (Aconiti Penduli et Aconiti Flavi Radix) on osteoarthritis rats and mechanisms.
Qi WANG ; Jing PENG ; Yang LIU ; Yang TIAN ; Jie LI ; Yao-Yao REN ; Jian GU ; Rui TAN
China Journal of Chinese Materia Medica 2022;47(17):4715-4722
This study aims to investigate the therapeutic effects of alkaloids in Tibetan medicine Bangna(Aconiti Penduli et Aconiti Flavi Radix) on osteoarthritis(OA) rats in vitro and in vivo and the underlying mechanisms. Chondrocytes were isolated from 2-3 week-old male SD rats and lipopolysaccharide(LPS) was used to induce OA in chondrocytes in vitro. Methyl thiazolyl tetrazolium(MTT) assay was used to investigate the toxicity of seven alkaloids(12-epi-napelline, songorine, benzoylaconine, aconitine, 3-acetylaconitine, mesaconitine, and benzoylmesaconine) to chondrocytes. Chondrocytes were classified into the control group, model group(induced by LPS 5 μg·mL~(-1) for 12 h), and administration groups(induced by LPS 5 μg·mL~(-1) for 12 h and incubated for 24 h). The protein expression of inflammatory factors cyclooxygenase-2(COX-2), inducible nitric oxide synthetase(iNOS), tumor necrosis factor-α(TNF-α), and interleukin-1β(IL-1β) in each group were detected by Western blot, and the protein expression of matrix metalloprotease-13(MMP-13), aggrecan, collagen Ⅱ, fibroblast growth factor 2(FGF2) by immunofluorescence staining. For the in vivo experiment, sodium iodoacetate was used to induce OA in rats, and the expression of MMP-13, TNF-α, and FGF2 in cartilage tissues of rats in each group was detected by immunohistochemistry. The results showed that the viability of chondrocytes could reach more than 90% under the treatment of the seven alkaloids in a certain dose range. Aconitine, 12-epi-napelline, songorine, 3-acetylaconitine, and mesaconitine could decrease the protein expression of inflammatory factors COX-2, iNOS, TNF-α and IL-1β compared with the model group. Moreover, 12-epi-napelline, aconitine, and mesaconitine could down-regulate the expression of MMP-13 and up-regulate the expression of aggrecan and collagen Ⅱ. In addition, compared with the model group and other Bangna alkaloids, 12-epi-napelline significantly up-regulated the expression of FGF2. Therefore, 12-epi-napelline was selected for the animal experiment in vivo. Immunohistochemistry results showed that 12-epi-napelline could significantly reduce the expression of MMP-13 and TNF-α in cartilage tissues, and up-regulate the expression of FGF2 compared with the model group. In conclusion, among the seven Bangna alkaloids, 12-epi-napelline can promote the repair of OA in rats by down-regulating the expression of MMP-13 and TNF-α and up-regulating the expression of FGF2.
Aconitine/therapeutic use*
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Aconitum/chemistry*
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Aggrecans/metabolism*
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Alkaloids/therapeutic use*
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Animals
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Cells, Cultured
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Cyclooxygenase 2/metabolism*
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Fibroblast Growth Factor 2/therapeutic use*
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Interleukin-1beta/metabolism*
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Iodoacetic Acid/therapeutic use*
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Lipopolysaccharides
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Male
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Matrix Metalloproteinase 13/metabolism*
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Medicine, Tibetan Traditional
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NF-kappa B/metabolism*
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Osteoarthritis/drug therapy*
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Rats
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Rats, Sprague-Dawley
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Tumor Necrosis Factor-alpha/metabolism*


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