1.Exploratory on Phase 0 Clinical Pharmacodynamics Trial in Chinese Materia Medica
Lizhe LIANG ; Guoxin LI ; Xuefeng YU
World Science and Technology-Modernization of Traditional Chinese Medicine 2017;19(5):851-857
Shu-Xue-Ning (SXN) injection was used as study subject in order to explore the feasibility of pharmacodynamics experiment of Phase 0 clinical trial in Chinese materia medica (CMM).This paper tried to establish key-technique standards which fit to the evaluation on CMM phase 0 (early) clinical evaluations.According to the established research methods,this research selected volunteers and assured low dose SXN injection inside their body.And then,serum before and after medication were collected for the HAEC in vitro experiment.Blood sample of the clinical dosage was used as control to verify the tendency consistency of pharmacodynamics in low dose and clinical dose.The results showed that in the H2O2 inducing HAEC damage experiment,low dose SXN injection can affect the cell proliferation,protect the shape of cells,reduce the release of ion owing to cell damages and influence the secretion in cells.Complete-sequence RNA gave differential multiterm expression before and after the low dose.It was concluded that compared with the clinical group,low dose medication had similar metabolic tendency.The pharmacodynamics experiment of phase 0 CMM clinical trial is feasible.
2.Establishment and preliminary analysis of fluid dynamics model of the subjects with micrognathia
Lizhe ZHU ; Bo YU ; Yu GUO ; Mingchao DING ; Yongming LI
Journal of Practical Stomatology 2015;(3):389-392
Objective:To establish a fluid dynamics model of upper airway before and after surgery and explore the changes of three-dimensional fluid dynamics in patients with micrognathia.Methods:A patient with micrognathia and severe obstructive sleep apnea-hypopnea syndrome(OSAHS)accepted CT scan before and six months after mandibular advancement operation.Computation-al fluid dynamics model was built on the base of CT scan by Mimics 1 0.01 and ANSYS ICEMCFD1 4.0.The internal flow of upper respiratory tract was simulated by ANSYS-FLUENT 1 4.0 and the results were analyzed by Tecplot.Results:Fluid dynamics model of upper airway was constructed before and after the surgery respectively.The volume of the upper airway of the patient increased from 37.284 cm3 to 44.498 cm3;the most narrow area of upper airway was located in the lower bound of pharyngopalatiae,and it was augmented from 1 .1 35 cm2 to 2.297 cm2;the minimum pressure was decreased from1 01 308 Pa to 1 01 272 Pa;the maximum air velocity increased from 3.476 m/s to 4.978 m/s.Conclusion:Mandibular advancement may correct the occlusal deformity,ex-panse the upper respiratory tract,decrease the negative pressure and maintain the patency of the airflow in the treatment of patients with micrognathia and OSAHS.
3.Gene mutation and protein expression of v-Raf murine sarcoma viral oncogene homolog B1 in esophageal cancer
Guangjie LIU ; Haoran ZHANG ; Shaonan XIE ; Lizhe LI ; Fang LIU ; Qingyi LIU
Chinese Journal of Digestion 2016;36(2):73-77
Objective To estimate the gene mutation and the protein expression of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) in esophageal cancer.Methods From February 2014 to September 2015,75 patients with esophageal cancer who received operation were enrolled.Tissues of cancer,adjacent to cancer and far from cancer were taken.The mutation and protein expression of BRAF were detected.The relationship between BRAF protein positive expression and clinical characteristics of patients with esophageal cancer was analyzed.The enumeration data was compared by chi-square test.Results The mutation of exon 11 and exon 15 of gene BRAF was not found in the tissues of esophageal cancer.Among 75 esophageal cancer,a base C or T inserted in the exon 11 was found in five Ⅲb TNM stage cases,and the expression of BRAF at protein level was positive in 46 cases (61.3%).Among 57 tissues adjacent to cancer,nine cases (15.8 %) was BRAF positive at protein level.Among 75 tissues far from cancer,five(6.7%) was BRAF positive at protein level.The difference among three groups was statistically significant (x2 =61.098,P<0.05).The positive rates of BRAF expression at protein level in patients with esophageal cancer at Ⅰ,Ⅱ and Ⅲ TNM stage were 21.7% (5/23),70.8% (17/24) and 85.7 % (24/28),respectively.The positive rates of BRAF expression at protein level in patients with and without lymph node metastasis were 81.6% (31/38) and 40.5% (15/37).The positive expression of BRAF at protein level was related with TNM stage and lymph node metastasis (x2 =23.136 and 13.313,both P<0.01),however it was not related with gender,age and the degree of tumor differentiation (all P>0.05).Conclusions There is base insertion in the exon 11 of gene BRAF in esophageal cancer,but gene mutation is not found.BRAF is highly expressed in esophageal cancer,which is related with TNM stage and lymph node metastasis,and BRAF could be an indicator of assessment of degree of malignancy and prognosis of esophageal cancer.
4.A new impulse noise filter based on pulse coupled neural network.
Yide MA ; Fei SHI ; Lian LI ; Lizhe AN
Journal of Biomedical Engineering 2004;21(6):1019-1023
This paper presents a new impulse noise filter based on pulse coupled neural networks according to the apparent difference of gray value between noised pixels and the pixels around them. Comparing with the state-of-the-art denoised PCNN filter, the step by step modifying algorithm based on PCNN also, the new PCNN filter suggested in this paper costs less computation and less execution time. At the same time this new PCNN filter has been compared with other nonlinear filters, such as median filter, the stack filter based on omnidirectional structural elements constrains, the Omnidirectional morphology Open-Closing maximum filter (OOCmax) and the Omnidirectional morphology Close-Opening minimum (OCOmin) filter. The results of simulation shows that this algorithm is superior to standard median filter, the state-of-the-art PCNN filter, the maximal, minimal morphological filter with omnidirectional structuring elements, and the optimal stack filter based on omnidirectional structural elements constrains in the aspect of the impulse noise removal. What is more important is that this algorithm can keep the details of images more effectively.
Computer Simulation
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Humans
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Neural Networks (Computer)
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Neurons
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cytology
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Plant Cells
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Pulse
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Signal Processing, Computer-Assisted
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instrumentation
5.A method based on image processing and analyzing technology for estimating the activity of mesenchymal stem cells.
Lizhe XIE ; Jiang WU ; Deyu LI ; Jiangli LIN ; Tianfu WANG ; Changqiong ZHENG
Journal of Biomedical Engineering 2006;23(2):279-281
Cell culture is one of the usual methods for studying living cell and tissue, the method presented in this paper is based on image processing and analyzing technology for activity estimation of mesenchymal stem cells (MSCs). The existing activity estimation methods are costly, complex and invasive. In this method, thresholding is used to preprocess image and to separate out the growth hallow. Then the area is calculated by counting the pixels of the growth hallow. The changes of the activity estimated by this method are similar to those by corresponding cellular experiments. Compared with the existing methods in biology, medicine or medical cellular science, this method is easier, faster, cost-effective and non-invasive. The proposed method has been proved to be efficient by primary experiments of MSCs.
Animals
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Cells, Cultured
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Femur
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cytology
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Image Processing, Computer-Assisted
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methods
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Mesenchymal Stromal Cells
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cytology
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Rats
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Rats, Sprague-Dawley
6.Antifungal efficacy of corneal collagen cross-linking on treating experimentally induced fungal keratitis of mice
Ziqian ZHU ; Shuanghao QIU ; Juan YUE ; Susu LIU ; Lizhe GU ; Hongmin ZHANG ; Zhijie LI ; Liya WANG
Chinese Journal of Experimental Ophthalmology 2018;36(5):344-350
Objective This study was to assess the efficacy of corneal collagen cross-linking treatment on fungal keratitis.Methods Eighty SPF male C57BL/6 mice aged 6-8 weeks were selected for the experiment.Fusarium solani infected model was established on the left eyes of all 80 mice.Forty mice were distributed randomly into sham operation group,model control group,scraped epithelium group and corneal collagen cross-linking (CXL)group (treated with epithelium scraped and CXL).Three days after modeling,the levels of the corncal disease sevcrity were scored by slit lamp microscopy.The fungal activity was confirmed by plate counts.The left 40 mice were divided randomly into sham operation group,model control group,scraped epithelium group and CXL group (treated with epithelium scraped and CXL).In 1 day and 2,3,4,5,6,7,14 days after modeling,the corneas were examined under the slit lamp microscope.The corneal pathological examination of each group were conducted with hematoxylin and eosin staining at postoperative 14 days.The animal feeding and use was in accordance with the standards set by the ARVO,and the experiment was approved by the Ethic Committee for Experimental Animal of Henan Eye Institute.Results The colony-forming units (CFUs) of fungal solutions in culture significantly decreased with CXL treatment (F =11.97,P =0.00).The Pearson correlation analysis of CFU and clinical scores in CXL group showed that inflammatory cells infiltration was positively correlated with corneal disease severity (r =0.723,P =0.043).Corneal inflammatory score was significantly lower in the CXL group in various time points,with a significant differences among the groups and time points (Fgroup =34.44,P=0.00;Ftime =17.49,P=0.00).Corneal lesion and the depth of ulceration in scraped epithelium group and CXL group were remarkably lower than that in the model control group (all at P < 0.05).Histopathology revealed that the degree of corneal collagen fibers destruction and the ratio of inflammatory cells infiltration in scraped epithelium group (59.33%) and CXL group (11.29%) were much lower than that in the model control group (73.65%).Conclusions CXL can inhibit the fungal activity effectively in the cornea of mice,and reduce the fungal induced keratitis reaction.
7.Risk factors for postoperative deep venous thrombosis in patients underwent craniotomy.
Renhua LI ; Na CHEN ; Chunyan YE ; Lizhe GUO ; E WANG ; Zhenghua HE
Journal of Central South University(Medical Sciences) 2020;45(4):395-399
OBJECTIVES:
To analyze the risk factors for postoperative deep vein thrombosis (DVT) in neurosurgical patients to provide the basis for the prevention of postoperative DVT.
METHODS:
A total of 141 patients underwent neurosurgery were enrolled. Thrombelastography (TEG) test was performed before and at the end of surgery. According to whether there was DVT formation after operation, the patients were divided into a thrombosis group and a non-thrombosis group. -test and rank sum test were used to compare the general clinical characteristics of the 2 groups, such as age, gender, intraoperative blood loss, -dimer, intraoperative crystal input, colloid input, blood product transfusion, operation duration, length of postoperative hospitalization. The application of chi-square test and rank-sum test were used to compared TEG main test indicators such as R and K values between the 2 groups. Logistic regression was used to analyze the possible risk factors for postoperative DVT in neurosurgical patients.
RESULTS:
There were significant differences in postoperative TEG index R, clotting factor function, intraoperative blood loss, hypertension or not, length of postoperative hospital stay, and postoperative absolute bed time (all <0.05). Logistic regression analysis showed hypercoagulability, more intraoperative blood loss and longer postoperative absolute bed time were risk factors for DVT formation after craniotomy.
CONCLUSIONS
Hypercoagulability in postoperative TEG test of patients is an important risk factor for the formation of postoperative DVT after neurosurgery, which can predict the occurrence of postoperative DVT to some extent.
Craniotomy
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adverse effects
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Humans
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Postoperative Complications
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epidemiology
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Postoperative Period
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Risk Factors
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Thrombophilia
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Venous Thrombosis
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epidemiology
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etiology
8.Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity
Guoshun LUO ; Zhenbang LI ; Xin LIN ; Xinyu LI ; Yu CHEN ; Kun XI ; Maoxu XIAO ; Hanlin WEI ; Lizhe ZHU ; Hua XIANG
Acta Pharmaceutica Sinica B 2021;11(5):1300-1314
HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC (