1.Identification of tissue distribution components and mechanism of antipyretic effect of famous classical formula Dayuanyin.
Yu-Jie HOU ; Kang-Ning XIAO ; Jian-Yun BI ; Xin-Rui LI ; Ming SU ; Li-Jie WANG ; Yu-Qing WANG ; Dan-Dan SUN ; Hui ZHANG ; Xin-Jun ZHANG ; Shan-Xin LIU
China Journal of Chinese Materia Medica 2025;50(10):2810-2824
Based on the ultra performance liquid chromatography-quadrupole Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology, combined with related literature, databases, and reference material information, this study qualitatively analyzed the components of Dayuanyin in the tissue of rats after gavage and employed molecular docking technology to predict the rationality of the mechanism behind the antipyretic effect of the in vivo components in Dayuanyin. A total of 21, 26, 20, 21, 14, and 31 prototype components and 3, 16, 3, 7, 5, and 24 metabolites were identified from the heart, liver, spleen, lung, kidney, and hypothalamus of the rats, respectively, and the binding ability of key components and targets was further verified by molecular docking. The results showed that all components had good binding ability with targets. The established UPLC-Q-Exactive Orbitrap-MS could effectively and quickly identify the Dayuanyin components distributed in tissue and preliminarily identify their metabolites. Many components were identified in the hypothalamus, which suggested that the components delivered to the brain should be focused on in the study on Dayuanyin in the treatment of febrile diseases. The molecular docking technology was used to predict the rationality of the mechanism behind its antipyretic effect, which lays the foundation for the clarification of the material basis and action mechanism of Dayuanyin, the development of new preparations, and the prediction of quality markers.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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Molecular Docking Simulation
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Male
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Antipyretics/metabolism*
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Rats, Sprague-Dawley
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Tissue Distribution
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Mass Spectrometry
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Chromatography, High Pressure Liquid
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Hypothalamus/metabolism*
2.Mechanism of Chaijin Jieyu Anshen Formula in regulating synaptic damage in nucleus accumbens neurons of rats with insomnia complicated with depression through TREM2/C1q axis.
Ying-Juan TANG ; Jia-Cheng DAI ; Song YANG ; Xiao-Shi YU ; Yao ZHANG ; Hai-Long SU ; Zhi-Yuan LIU ; Zi-Xuan XIANG ; Jun-Cheng LIU ; Hai-Xia HE ; Jian LIU ; Yuan-Shan HAN ; Yu-Hong WANG ; Man-Shu ZOU
China Journal of Chinese Materia Medica 2025;50(16):4538-4545
This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals
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Male
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Rats
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Nucleus Accumbens/metabolism*
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Drugs, Chinese Herbal/administration & dosage*
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Depression/complications*
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Membrane Glycoproteins/genetics*
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Rats, Sprague-Dawley
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Sleep Initiation and Maintenance Disorders/complications*
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Neurons/metabolism*
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Receptors, Immunologic/genetics*
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Signal Transduction/drug effects*
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Synapses/metabolism*
4.Pharmacokinetics study of Dayuanyin in normal and febrile rats.
Yu-Jie HOU ; Kang-Ning XIAO ; Jian-Yun BI ; Xin-Jun ZHANG ; Xin-Rui LI ; Yu-Qing WANG ; Ming SU ; Xin-Ru SUN ; Hui ZHANG ; Bo-Yang WANG ; Li-Jie WANG ; Shan-Xin LIU
China Journal of Chinese Materia Medica 2025;50(2):527-533
Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals
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Rats
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Drugs, Chinese Herbal/administration & dosage*
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Male
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Rats, Sprague-Dawley
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Fever/metabolism*
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Tandem Mass Spectrometry
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Chromatography, High Pressure Liquid
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Glucosides/pharmacokinetics*
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Monoterpenes
5.Colon Dialysis with Yishen Decoction Improves Autophagy Disorder in Intestinal Mucosal Epithelial Cells of Chronic Renal Failure by Regulating SIRT1 Pathway.
Yan-Jun FAN ; Jing-Ai FANG ; Su-Fen LI ; Ting LIU ; Wen-Yuan LIU ; Ya-Ling HU ; Rui-Hua WANG ; Hui LI ; Da-Lin SUN ; Guang ZHANG ; Zi-Yuan ZHANG
Chinese journal of integrative medicine 2025;31(10):899-907
OBJECTIVE:
To explore the mechanism of colon dialysis with Yishen Decoction (YS) in improving the autophagy disorder of intestinal epithelial cells in chronic renal failure (CRF) in vivo and in vitro.
METHODS:
Thirty male SD rats were randomly divided into normal, CRF, and colonic dialysis with YS groups by a random number table method (n=10). The CRF model was established by orally gavage of adenine 200 mg/(kg•d) for 4 weeks. CRF rats in the YS group were treated with colonic dialysis using YS 20 g/(kg•d) for 14 consecutive days. The serum creatinine (SCr) and urea nitrogen (BUN) levels were detected by enzyme-linked immunosorbent assay. Pathological changes of kidney and colon tissues were observed by hematoxylin and eosin staining. Autophagosome changes in colonic epithelial cells was observed with electron microscopy. In vitro experiments, human colon cancer epithelial cells (T84) were cultured and divided into normal, urea model (74U), YS colon dialysis, autophagy activator rapamycin (Ra), autophagy inhibitor 3-methyladenine (3-MA), and SIRT1 activator resveratrol (Re) groups. RT-PCR and Western blot were used to detect the mRNA and protein expressions of zonula occludens-1 (ZO-1), Claudin-1, silent information regulator sirtuin 1 (SIRT1), LC3, and Beclin-1 both in vitro and in vivo.
RESULTS:
Colonic dialysis with YS decreased SCr and BUN levels in CRF rats (P<0.05), and alleviated the pathological changes of renal and colon tissues. Expressions of SIRT1, ZO-1, Claudin-1, Beclin-1, and LC3II/I were increased in the YS group compared with the CRF group in vivo (P<0.05). In in vitro study, compared with normal group, the expressions of SIRT1, ZO-1, and Claudin-1 were decreased, and expressions of Beclin-1, and LC3II/I were increased in the 74U group (P<0.05). Compared with the 74U group, expressions of SIRT1, ZO-1, and Claudin-1 were increased, whereas Beclin-1, and LC3II/I were decreased in the YS group (P<0.05). The treatment of 3-MA and rapamycin regulated autophagy and the expression of SIRT1. SIRT1 activator intervention up-regulated autophagy as well as the expressions of ZO-1 and Claudin-1 compared with the 74U group (P<0.05).
CONCLUSION
Colonic dialysis with YS could improve autophagy disorder and repair CRF intestinal mucosal barrier injury by regulating SIRT1 expression in intestinal epithelial cells.
Animals
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Sirtuin 1/metabolism*
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Drugs, Chinese Herbal/therapeutic use*
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Autophagy/drug effects*
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Male
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Intestinal Mucosa/drug effects*
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Rats, Sprague-Dawley
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Epithelial Cells/metabolism*
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Colon/drug effects*
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Humans
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Kidney Failure, Chronic/drug therapy*
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Signal Transduction/drug effects*
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Renal Dialysis
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Rats
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Kidney/drug effects*
6.Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024)
Xiao CHEN ; Hao ZHANG ; Man WANG ; Guangchao WANG ; Jin CUI ; Wencai ZHANG ; Fengjin ZHOU ; Qiang YANG ; Guohui LIU ; Zhongmin SHI ; Lili YANG ; Zhiwei WANG ; Guixin SUN ; Biao CHENG ; Ming CAI ; Haodong LIN ; Hongxing SHEN ; Hao SHEN ; Yunfei ZHANG ; Fuxin WEI ; Feng NIU ; Chao FANG ; Huiwen CHEN ; Shaojun SONG ; Yong WANG ; Jun LIN ; Yuhai MA ; Wei CHEN ; Nan CHEN ; Zhiyong HOU ; Xin WANG ; Aiyuan WANG ; Zhen GENG ; Kainan LI ; Dongliang WANG ; Fanfu FANG ; Jiacan SU
Chinese Journal of Trauma 2024;40(3):193-205
Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.
7.Study on the catalytic mechanism of triterpene C-29 carboxylases from Tripterygium wilfordii based on directed evolution
Pan-ting LIU ; Yi-feng ZHANG ; Yuan LIU ; Jie GAO ; Lin MA ; Xiao-yi WU ; Ya-ting HU ; Ping SU ; Shi-jun YUAN ; Xia-nan ZHANG ; Wei GAO
Acta Pharmaceutica Sinica 2024;59(6):1883-1893
Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from
8.Correlation of platelet parameter changes and prognosis in children with severe community-acquired pneumonia
Yiyang MAO ; Suyun QIAN ; Hengmiao GAO ; Boliang FANG ; Rubo LI ; Guoyun SU ; Jun LIU ; Gang LIU ; Chaonan FAN
Chinese Pediatric Emergency Medicine 2024;31(2):120-125
Objective:To investigate the dynamic trend of platelet(PLT)count and mean platelet volume(MPV)in children with severe community-acquired pneumonia(SCAP)in PICU and their correlation with prognosis.Methods:A retrospective study was conducted in 215 SCAP children who were admitted to the PICU of Beijing Children's Hospital Affiliated to Capital Medical University from January 2016 to December 2019.According to the disease outcome,the patients were divided into improvement group ( n=184) and unrecovered group ( n=31).The changes of PLT count and MPV at admission,on the 2nd,3rd,and 7th days of hospitalization and before discharge were observed,and the relationship between changes in PLT parameters and poor prognosis was analyzed. Meanwhile,the correlation between thrombocytopenia on admission and on the 7th day of hospitalization and prognosis was further explored. Results:The PLT count of improvement group at admission,on the 2nd,3rd,and 7th days of hospitalization and at discharge[(328±159, 329±137, 362±159, 439±168, 510±171)×10 9/L] were significantly higher than those of unrecovered group [(210±142, 207±152, 267±143, 260±162, 343±159)×10 9/L]( P<0.05).Although the MPV of improvement group [(10.9±1.9)fL] on admission was significantly lower than that of the unrecovered group[(12.7±2.5) fL]( P<0.05),there was no significant difference in MPV between two groups on the 2nd,3rd,7th days of hospitalization and discharge( P>0.05).In addition,compared with the admission,children in improvement group had significantly higher PLT count on the 7th day of hospitalization and before discharge( P<0.05),but there was no significant change in unrecovered group( P>0.05).Compared with SCAP patients with thrombocytopenia at admission (PLT<100×10 9/L)( n=22),those with thrombocytopenia on 7th day of hospitalization had a significant higher rate of non recovery( P<0.05). Conclusion:The occurrence of thrombocytopenia on admission and after 7 days of hospitalization in children with SCAP is associated with poor prognosis.No significant increase or decrease in PLT count after 7 days of hospitalization is often indicative of poor prognosis.Dynamic monitoring of PLT parameter changes may help to better judge the prognosis of severe pneumonia.
9.Mechanism of Xibining Ⅱ Combined with ADSC-Exos in Improving Knee Osteoarthritis by Regulating Mitochondrial Autophagy
Junfeng KANG ; Lishi JIE ; Houyu FU ; Taiyang LIAO ; Lei SHI ; Zishan SU ; Likai YU ; Yibao WEI ; Deren LIU ; Di TIAN ; Jun MAO ; Peimin WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(11):111-119
ObjectiveTo observe the effects of Xibining (XBN) and adipose stem cell exosome (ADSC-Exos) in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis (KOA). MethodSD rats were divided into a sham operation group (sham group), a model group, an ADSC-Exos group (Exos group), an XBN group, and an ADSC-Exos+XBN group (Exos+XBN group). KOA model was established by using anterior cruciate ligament transection (ACLT). The pain sensitivity status of rats was evaluated, and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence, and the serum levels of TNF-α, IL-1β, IL-6, and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3, MMP-13, ADAMTS5, ColⅡ, TIMP, ACAN, PINK1, Parkin, p62, and LC3A/B. ResultCompared with the sham group, rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, varying degrees of abrasion and loss of cartilage tissue, degeneration of cartilage tissue, elevated serum IL-1β, IL-6, IL-15, and TNF-α levels (P<0.01), and increased protein expression of MMP-3, MMP-13, and ADAMTS5 in cartilage tissue. In addition, the protein expression of ColⅡ, TIMP1, and ACAN was decreased (P<0.01). Compared with the model group, rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds, reduced cartilage tissue degeneration, lower serum levels of IL-1β, IL-6, IL-15, and TNF-α (P<0.05,P<0.01), decreased protein expression of MMP-3, MMP-13, and ADAMTS5, and higher protein expression of Cold, TIMP1, and ACAN in cartilage tissue (P<0.05,P<0.01). Moreover, the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway, and the combination of the two can enhance the therapeutic effect.
10.Development of the robotic digestive endoscope system and an experimental study on mechanistic model and living animals (with video)
Bingrong LIU ; Yili FU ; Kaipeng LIU ; Deliang LI ; Bo PAN ; Dan LIU ; Hao QIU ; Xiaocan JIA ; Jianping CHEN ; Jiyu ZHANG ; Mei WANG ; Fengdong LI ; Xiaopeng ZHANG ; Zongling KAN ; Jinghao LI ; Yuan GAO ; Min SU ; Quanqin XIE ; Jun YANG ; Yu LIU ; Lixia ZHAO
Chinese Journal of Digestive Endoscopy 2024;41(1):35-42
Objective:To develop a robotic digestive endoscope system (RDES) and to evaluate its feasibility, safety and control performance by experiments.Methods:The RDES was designed based on the master-slave control system, which consisted of 3 parts: the integrated endoscope, including a knob and button robotic control system integrated with a gastroscope; the robotic mechanical arm system, including the base and arm, as well as the endoscopic advance-retreat control device (force-feedback function was designed) and the endoscopic axial rotation control device; the control console, including a master manipulator and an image monitor. The operator sit far away from the endoscope and controlled the master manipulator to bend the end of the endoscope and to control advance, retract and rotation of the endoscope. The air supply, water supply, suction, figure fixing and motion scaling switching was realized by pressing buttons on the master manipulator. In the endoscopy experiments performed on live pigs, 5 physicians each were in the beginner and advanced groups. Each operator operated RDES and traditional endoscope (2 weeks interval) to perform porcine gastroscopy 6 times, comparing the examination time. In the experiment of endoscopic circle drawing on the inner wall of the simulated stomach model, each operator in the two groups operated RDES 1∶1 motion scaling, 5∶1 motion scaling and ordinary endoscope to complete endoscopic circle drawing 6 times, comparing the completion time, accuracy (i.e. trajectory deviation) and workload.Results:RDES was operated normally with good force feedback function. All porcine in vivo gastroscopies were successful, without mucosal injury, bleeding or perforation. In beginner and advanced groups, the examination time of both RDES and ordinary endoscopy tended to decrease as the number of operations increased, but the decrease in time was greater for operating RDES than for operating ordinary endoscope (beginner group P=0.033; advanced group P=0.023). In the beginner group, the operators operating RDES with 1∶1 motion scaling or 5∶1 motion scaling to complete endoscopic circle drawing had shorter completion time [1.68 (1.40, 2.17) min, 1.73 (1.47, 2.37) min VS 4.13 (2.27, 5.16) min, H=32.506, P<0.001], better trajectory deviation (0.50±0.11 mm, 0.46±0.11 mm VS 0.82±0.26 mm, F=38.999, P<0.001], and less workload [42.00 (30.00, 50.33) points, 43.33 (35.33, 54.00) points VS 52.67 (48.67, 63.33) points, H=20.056, P<0.001] than operating ordinary endoscope. In the advanced group, the operators operating RDES with 1∶1 or 5∶1 motion scaling to complete endoscopic circle drawing had longer completion time than operating ordinary endoscope [1.72 (1.37, 2.53) min, 1.57 (1.25, 2.58) min VS 1.15 (0.86, 1.58) min, H=13.233, P=0.001], but trajectory deviation [0.47 (0.13, 0.57) mm, 0.44 (0.39, 0.58) mm VS 0.52 (0.42, 0.59) mm, H=3.202, P=0.202] and workload (44.62±21.77 points, 41.24±12.57 points VS 44.71±17.92 points, F=0.369, P=0.693) were not different from those of the ordinary endoscope. Conclusion:The RDES enables remote control, greatly reducing the endoscopists' workload. Additionally, it gives full play to the cooperative motion function of the large and small endoscopic knobs, making the control more flexible. Finally, it increases motion scaling switching function to make the control of endoscope more flexible and more accurate. It is also easy for beginners to learn and master, and can shorten the training period. So it can provide the possibility of remote endoscopic control and fully automated robotic endoscope.

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