1.Logic-gated tumor-microenvironment nanoamplifier enables targeted delivery of CRISPR/Cas9 for multimodal cancer therapy.
Yongchun PAN ; Xiaowei LUAN ; Fei ZENG ; Xuyuan WANG ; Shurong QIN ; Qianglan LU ; Guanzhong HE ; Yanfeng GAO ; Xiaolian SUN ; Xin HAN ; Bangshun HE ; Yujun SONG
Acta Pharmaceutica Sinica B 2024;14(2):795-807
		                        		
		                        			
		                        			Recent innovations in nanomaterials inspire abundant novel tumor-targeting CRISPR-based gene therapies. However, the therapeutic efficiency of traditional targeted nanotherapeutic strategies is limited by that the biomarkers vary in a spatiotemporal-dependent manner with tumor progression. Here, we propose a self-amplifying logic-gated gene editing strategy for gene/H2O2-mediated/starvation multimodal cancer therapy. In this approach, a hypoxia-degradable covalent-organic framework (COF) is synthesized to coat a-ZIF-8 in which glucose oxidase (GOx) and CRISPR system are packaged. To intensify intracellular redox dyshomeostasis, DNAzymes which can cleave catalase mRNA are loaded as well. When the nanosystem gets into the tumor, the weakly acidic and hypoxic microenvironment degrades the ZIF-8@COF to activate GOx, which amplifies intracellular H+ and hypoxia, accelerating the nanocarrier degradation to guarantee available CRISPR plasmid and GOx release in target cells. These tandem reactions deplete glucose and oxygen, leading to logic-gated-triggered gene editing as well as synergistic gene/H2O2-mediated/starvation therapy. Overall, this approach highlights the biocomputing-based CRISPR delivery and underscores the great potential of precise cancer therapy.
		                        		
		                        		
		                        		
		                        	
2.Clinical Observation of Yinlian Gargle in the Prevention and Treatment of Acute Radiation-Induced Oropharyngeal Mucositis After Nasopharyngeal Carcinoma Radiotherapy
Caishan FANG ; Peiqi XIAO ; Yu ZHONG ; Yongchun WANG ; Chiming ZHANG ; Min ZHOU ; Yajie YAN ; Yan RUAN
Traditional Chinese Drug Research & Clinical Pharmacology 2024;35(1):141-147
		                        		
		                        			
		                        			Objective To observe the clinical efficacy of Yinlian Gargle in the treatment of acute radiation-induced oropharyngeal mucositis after nasopharyngeal carcinoma radiotherapy.Methods Thirty-two patients with nasopharyngeal carcinoma,who had received first radiation,were randomly split into two groups:the trial group(19 cases)and the control group(13 cases).After all groups were treated with radiotherapy and chemotherapy,the control group was given rinse treatment with saline whereas the trial group was given Yinlian Gargle.The incidence of severe acute radiation-induced oropharyngeal mucositis,the duration and intensity of oropharyngeal discomfort and pain(NRS score),quality of life(QOL-NPC score),duration and intensity of radiation-induced side effects(SE-QOL-NPC score)and symptoms of dry mouth(SE1 score)were monitored before and after intervention in two groups.Results The incidence of grade Ⅲ or above radiation-induced oropharyngeal mucositis until the sixth week of radiotherapy in the trial group was considerably lower than that in the control group(P<0.001),while the incidence of grade I or above radiation-induced oropharyngeal mucositis at 1 month after radiotherapy in the trial group was obviously lower than that in the control group(P<0.001).The NRS score of pharyngeal discomfort of the trial group was lower than that of the control group starting from the second week of radiotherapy(P<0.05).The NRS score of oral and oropharyngeal pain was lower than that of the control group starting from the fourth week of radiotherapy(P<0.05).The SE1 score of the trial group was higher than that of the control group starting from the fifth week of radiotherapy(P<0.05).After one month of the completion of the radiotherapy,the NRS score of pharyngeal discomfort and the NRS score of oral and oropharyngeal pain in the trial group were lower than those of the control group(P<0.001).The QOL-NPC score,SE-QOL-NPC score,and SE1 score were all higher than those in the control group(P = 0.05 or P<0.05).Conclusion Patients with nasopharyngeal cancer can greatly reduce their risk of developing severe acute radiation-induced oropharyngeal mucositis,effectively delay and relieve related symptoms,and enhance quality of life by consistently using Yinlian Gargle during radiotherapy.Additionally,a month after the completion of radiotherapy,it still has positive therapeutic effects on acute radiation-induced oropharyngeal mucositis.
		                        		
		                        		
		                        		
		                        	
3.Research progress in perioperative nursing for patients undergoing neurointerventional therapy via radial artery access
Wenlong PAN ; Fang WANG ; Yongchun LUO
Journal of Interventional Radiology 2024;33(10):1142-1146
		                        		
		                        			
		                        			In recent years,with the rapid development of minimally-invasive interventional therapy technology,the effectiveness of neurointerventional therapy through radial artery puncture has been highlighted in clinical application.Compared with the commonly-used femoral artery puncture,transradial access can let the patients have a better comfort and willingness to accept the operation,which can also reduce postoperative complications and improve the quality of diagnosis and treatment.However,the perioperative nursing measures have always been based on the measures used in coronary interventional therapy,the nursing measures of neurointerventional therapy are still in the experience summary stage,and there is still a lack of unified,normative and guiding documents for formulating the clinical nursing care.This paper reviews the perioperative nursing measures of neurointerventional procedures via radial artery puncture,focusing on the advantages of radial artery puncture approach,the key points of preoperative care assessment,the intraoperative nursing strategy,the prevention and treatment of postoperative complications,etc.so as to provide evidence-based references for clinical nursing practice.
		                        		
		                        		
		                        		
		                        	
4.The early warning value of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure in patients with pressure injury in ICU
Zhiqiang GUO ; Jian LAN ; Yili DENG ; Xiaochuan WANG ; Yun WANG ; Yongchun WANG
Chinese Journal of Emergency Medicine 2024;33(5):698-703
		                        		
		                        			
		                        			Objective:To investigate the early warning value of transcutaneous oxygen pressure and transcutaneous carbon dioxide pressure (TcPO 2/TcPCO 2) monitoring in patients with pressure injury in ICU. Methods:A prospective clinical observation study was conducted. Patients were selected in the department of critical care medicine of Shenzhen Hospital Affiliated to University of Chinese Academy of Sciences from December 2020 to June 2022. The general information of all patients were recorded. The data of TcPO 2 and TcPCO 2 were monitored respectively in left lying position, supine position and right lying position. According to the Braden score of patients, they were divided into low risk group and high risk group, and the monitoring results of TcPO 2/TcPCO 2 were analyzed. Results:The study included a total of 80 patients, with 46 patients in the low risk group and 34 patients in the high risk group. There were no significant differences in gender and age between the two groups (both P>0.05). There were significant differences in the Braden score and the incidence of pressure injury between the two groups (both P<0.05). There were statistically significant differences in TcPO 2 at various time points in the left lying position, supine position and right lying position between the low risk and the high risk groups (all P<0.001). Except for the 15th minute of the left lying position and right lying position, there were statistically significant differences in TcPCO2 at all other time points in the supine and right lying positions between two groups (all P<0.05). There were statistically significant differences in TcPO 2/TcPCO 2 values at various time points in different positions between two groups (all P<0.001). In supine position, TcPO 2 and TcPO 2/TcPCO 2 were positively correlated with the Braden score ( r=0.680, 0.741). TcPCO 2 was negatively correlated with the Braden score ( r=-0.771). The Braden score, TcPO 2, TcPCO 2 and TcPO 2/TcPCO 2 all have moderate diagnostic value. The cut-off values were 12.50, 41.48 mmHg, 52.29 mmHg and 0.91, respectively. And the AUC were 0.899, 0.727, 0.816 and 0.719, respectively. However, there were no significant differences in AUC between the TcPO 2, TcPCO 2, TcPO 2/TcPCO 2 and Braden score (all P>0.05). Conclusions:TcPO 2, TcPCO 2 and TcPO 2/TcPCO 2 values all have higher diagnostic value about pressure injury for patients in ICU. TcPO 2/TcPCO 2 monitoring has early risk warning value for the occurrence of pressure injury in ICU, which is worthy of clinical promotion.
		                        		
		                        		
		                        		
		                        	
5.Applicability evaluation of resting energy expenditure estimation equations for elderly people in pension institution
Lu WANG ; Mengjia YUE ; Yuchang TAO ; Tingting YANG ; Hongyan DUAN ; Yongchun CHEN
Journal of Clinical Medicine in Practice 2024;28(23):91-95
		                        		
		                        			
		                        			Objective To compare the consistency between the estimated values of nine common resting energy expenditure estimation equations and the measured values among the elderly population in pension institutions. Methods A total of 181 elderly individuals from Henan Guangda Ouan Leling Nursing Center were recruited as study objects through cluster sampling. The differences between the estimated values of nine common equations and the measured values obtained by indirect calorimetry were compared, and subgroup analyses were conducted to compare their consistency across different subgroups. Results Among the nine equations, the Cunningham equation and the Owen equation showed relatively small deviations from the measured values, with no significant differences (deviation rates of -1.9% and -2.0%, root mean square errors of 222.7 kcal/d and 239.4 kcal/d, and coincidence rates of 48.4% and 47.5%, respectively). In subgroups stratified by gender and body mass index (BMI), the Cunningham equation showed no significant difference compared with the measured values. The Owen equation showed no significant difference compared with the measured values only in some subgroups [males with BMI of 20~ < 27 kg/m2 and ≥27 kg/m2, and females with BMI < 20 kg/m2]. Conclusion The Cunningham equation, which utilizes body composition data, can assess the resting energy expenditure of the elderly in pension institutions with relatively high accuracy and speed, demonstrating strong applicability in this population.
		                        		
		                        		
		                        		
		                        	
6.Pharmacodynamic Material Basis of Astragali Radix and Angelicae Sinensis Radix Drug Pair in Supplementing Qi and Activating Blood Circulation
Shan LIU ; Wenyue WANG ; Yongchun WANG ; Kaiyong XU ; Dandan XU ; Jialin TENG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):28-36
		                        		
		                        			
		                        			ObjectiveTo evaluate the effect of Astragali Radix (AR)-Angelicae Sinensis Radix (ASR) drug pair on supplementing Qi and activating blood circulation in rats with Qi deficiency and blood stasis and provide a theoretical basis for clinical rational medication and identification and quality control of compound pharmacodynamic substances from the three aspects of characteristic map, identification of pharmacodynamic substances, and comparison of blood components. MethodHigh-performance liquid chromatography (HPLC) was employed to establish the fingerprint of AR∶ASR (3∶1), and ultra-high performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry (UPLC-Q-Exactive Orbitrap-MS) was employed to analyze the ingredients of the decoction. Adult male Wistar rats with SPF grades were selected and randomly divided into a blank group, a model group, a 3∶1 group, and a 5∶1 group. The rat model of Qi deficiency and blood stasis syndrome was prepared by controlling food intake and swimming in cold water every day. In parallel, each group was given medicine (or water) once a day. The dose of drug groups was 10.2 g∙kg-1, and the model group and blank group were given the same amount of distilled water for 15 d. Animal behavior, body weight, whole blood and plasma viscosity, thymus index, spleen index, the levels of adenosine triphosphate (ATP), adenosine diphosphate(ADP), von willebrand factor (vWF), and ATP/ADP value in serum of rats were recorded. The morphology of vascular endothelium was observed by hematoxylin-eosin (HE) staining and scanning electron microscopy. UPLC-Q-Exactive Orbitrap-MS was used to analyze prototype and metabolic components in serum. ResultThe fingerprint of AR-ASR drug pair (AR-ASR 3∶1) was established. UPLC-Q-Exactive Orbitrap MS identified 49 chemical components in vitro and preliminarily identified 11 prototype components absorbed into blood in vivo. As compared with the blank group, the body mass decreased significantly (P<0.01), the whole blood (high shear, middle shear, and low shear) viscosity and plasma viscosity were significantly increased (P<0.05, P<0.01), the thymus index and spleen index decreased significantly (P<0.05, P<0.01), serum ATP content decreased significantly (P<0.01), ADP content increased significantly (P<0.01), ATP/ADP value decreased significantly (P<0.01), and vWF content increased significantly (P<0.01). The results of HE staining and scanning electron microscopy showed that the vessels were partially damaged, showing the structural disorder of the intima, the bulge, defect, and roughness of the endothelium, and the obvious cell adhesion and migration in the model group. As compared with the model group, the body mass also increased significantly (P<0.01). The results of whole blood and plasma viscosity showed that the whole blood low shear viscosity was significantly decreased in the 3∶1 group (P<0.05). The results of thymus index and spleen index showed that 5∶1 group significantly increased the thymus index of rats (P<0.05). The results of serum ATP and ADP levels showed that the 5∶1 group had more significant effects on ATP and ADP levels (P<0.05), and both groups significantly reduced ATP/ADP values (P<0.01). The results of serum vWF level showed that the vWF content in the 3∶1 group decreased significantly (P<0.05). The results of HE staining and scanning electronic microscopy showed that the damage of vascular endothelium was improved in the treatment group and the structure of intima was neat. ConclusionAR-ASR drug pair can improve the macro and micro indexes of rats with qi deficiency and blood stasis in the 3∶1 and 5∶1 groups. Overall, the 5∶1 ratio has a better effect on supplementing Qi but 3∶1 ratio has a better effect on promoting blood circulation. 
		                        		
		                        		
		                        		
		                        	
7.Design and Research of Wearable Fall Protection Device for the Elderly.
Jie WANG ; Yeke SUN ; Zhenglong CHEN ; Yongchun JIN ; Yunhua XU
Chinese Journal of Medical Instrumentation 2023;47(3):278-283
		                        		
		                        			
		                        			A protective device was designed that can be worn on the elderly, which consists of protective airbag, control box and protective mechanism. The combined acceleration, combined angular velocity and human posture angle are selected as the parameters to determine the fall, and the threshold algorithm and SVM algorithm are used to detect the fall. The protective mechanism is an inflatable device based on CO2 compressed air cylinder, and the equal-width cam structure is applied to its transmission part to improve the puncture efficiency of the compressed gas cylinder. A fall experiment was designed to obtain the combined acceleration and angular velocity eigenvalues of fall actions (forward fall, backward fall and lateral fall) and daily activities (sitting-standing, walking, jogging and walking up and down stairs), showing that the specificity and sensitivity of the protection module reached 92.1% and 84.4% respectively, which verified the feasibility of the fall protection device.
		                        		
		                        		
		                        		
		                        			Humans
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		                        			Aged
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		                        			Monitoring, Ambulatory
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		                        			Activities of Daily Living
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		                        			Wearable Electronic Devices
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		                        			Walking
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		                        			Acceleration
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		                        			Algorithms
		                        			
		                        		
		                        	
8.Emerging trends in organ-on-a-chip systems for drug screening.
Yanping WANG ; Yanfeng GAO ; Yongchun PAN ; Dongtao ZHOU ; Yuta LIU ; Yi YIN ; Jingjing YANG ; Yuzhen WANG ; Yujun SONG
Acta Pharmaceutica Sinica B 2023;13(6):2483-2509
		                        		
		                        			
		                        			New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.
		                        		
		                        		
		                        		
		                        	
9.Progress in use of pigs as model animals
Yan WANG ; Yongchun CAO ; Kai XING
Acta Laboratorium Animalis Scientia Sinica 2023;31(12):1636-1645
		                        		
		                        			
		                        			Animal models of human diseases include experimental animals and related materials established during biomedical research,which in turn play a vital role in medical research.Pigs and humans are similar in terms of their anatomy,physiology,immunology,and genetics.Pigs are thus suitable model animals for biomedical research and have various advantages compared with other model animals.Recent advances in biotechnology,such as genetic engineering,have contributed to a rapid increase in the use of pig models for human disease research.In addition to serving as xenotransplant organ donors and as tools in drug-design studies,pigs can also be used as model animals to study human developmental processes,congenital diseases,and disease-response mechanisms,thus making important contributions to improving human health.This review considers the current status and future applications of pigs as research models for studies of human cardiovascular diseases,cancer,ophthalmology,craniofacial,musculoskeletal,and skin research,reproductive and fetal development,nutrition,microbiome research,brain and neurodegenerative diseases,diabetes,infectious diseases,and vaccine design,as well as for xenotransplantation.
		                        		
		                        		
		                        		
		                        	
10.Construction and Verification of Quality Evaluation Indicator System for Extracorporeal Membrane Oxygenation Animal Experimental Platform
Shuo WANG ; Yunhui LÜ ; Xiaokang WANG ; Zhenhao ZHANG ; Yongchun CUI
Laboratory Animal and Comparative Medicine 2023;43(6):604-611
		                        		
		                        			
		                        			 ObjectiveTo establish a standardized and professional service quality evaluation index system for extracorporeal membrane oxygenation (ECMO) animalexperimental platform.Methods The literature research and expert consultation were used to establish a factor set for the quality evaluation of ECMO animal experimental platform. Then, experts used the 1/9-9 scale method to compare and score pair-two indicators. Based on the principles of fuzzy analytic hierarchy process and expert scoring results, the ECMO animal experimental platform quality evaluation system was constructed. In order to verify the actual efficacy of this system, a case study was carried out on the ECMO animal experiment platform of FW Animal Experimental Center (FAEC) laboratory.Results A total of 10 experts were included in this study, the questionnaire recovery rate was 100%, the judgment coefficient (Ca) and familiarity coefficient (Cs) were both greater than 0.50, the expert authority was high (Cr>0.80), the validity test was P<0.01, and the coordination was good. The quality evaluation system of ECMO animal experiment platform includes two levels. There are 4 first-level indicators, with professionalism, safety, functionality, and stability ranked from high to low in terms of their weights. There are 15 second-level indicators, and the top 5 weights are personnel's technical expertise, attractiveness of hardware facility, auditability of data, confidentiality capabilities of data, and professionalism in service process. To facilitate the popularization and application of the system, this study also proposed a "star" system to represent the evaluation results of an ECMO animal experimental platform quality. The quality evaluation system established in this study was used to evaluate the FAEC laboratory as a case study, and the evaluation result was five-star. The actual potency value of FAEC laboratory was 0.910, reaching the five-star level, but the average actual appraisal valuesof "service continuity" and "sufficiency of project completion" were lower than 0.80, which needs to be improved.ConclusionA standardized and professional ECMO animal experimental platform quality evaluation system was established in this study, which would provide a measurable basis for the demander to select the supplier and a method for the supplier to complete the animal experiment of ECMO research and development with high quality.
		                        		
		                        		
		                        		
		                        	
            

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