1.Exploring the management innovation mechanisms of emergency science and technology research projects in the medical field
Yujun CHEN ; Meiyangyi SU ; Qingxuan WANG ; Ran GAO
Chinese Journal of Comparative Medicine 2024;34(3):102-110
Objective Emergency technology research projects have two key aspects,"emergency"and"research",but it is not always clear how to effectively achieve the desired result.Organizations that undertake emergency technology research projects need to develop reasonable project management mechanisms to ensure their successful implementation.In this study,we investigated the current problems faced by those managing emergency technology research projects in the medical field.We researched and analyzed possible measures to improve the efficiency and quality of scientific research management.Methods This study leveraged the author's practical experience to investigate the current status of scientific research management in relevant units.Questionnaire surveys were conducted to ascertain the management aspects that most concern scientific managers and researchers.The problems raised by the survey were categorized and discussed.Results Through the research,we found that(1)at present,there are few management standards for emergency technology research projects;(2)the issue of greatest concern for scientific researchers is administrative approval and project funding;(3)the issue of greatest concern for scientific management personnel is how to meet the management requirements of higher-level units and the needs of scientific researchers under the premise of legal compliance.Conclusions Emergency technology research projects have unique characteristics distinct from those of conventional technology projects.Management optimization can be carried out in terms of project approval,funding use,resource allocation,and safety.This study has provided innovative solutions to improve the management of emergency technology research projects and a useful reference of the experiences of various scientific research units in managing such projects.
2.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.
3.Multi-course Iodine-131-meta-iodobenzylguanidine in the treatment of metastatic paraganglioma: a case report
Yun LI ; Hongbo GAO ; Longmin LI ; Yujun SHAO ; Xiayang ZHU
Clinical Medicine of China 2024;40(2):114-119
Paraganglioma (PGL) is a rare neuroendocrine tumor that causes endocrine hypertension. All paragangliomas had metastatic potential. The 5-year survival rate of patients with metastatic paraganglioma is less than 50%, and the treatment is a big problem. Metastatic PGL has a high specific uptake of iodine [ 131I]-meta-iodobenzylguanidine ( 131I-MIBG), so the treatment is effective, well tolerated, and has few adverse reactions. However, there is a lack of relevant detailed clinical diagnosis and treatment data in China. This article reports the diagnosis and treatment of a case of multi-site metastatic paraganglioma with multiple courses of 131I-MIBG, and discusses the efficacy, safety and tolerance of the treatment for clinical reference.
4.Sequential delivery of PD-1/PD-L1 blockade peptide and IDO inhibitor for immunosuppressive microenvironment remodeling via an MMP-2 responsive dual-targeting liposome.
Chuan HU ; Yujun SONG ; Yiwei ZHANG ; Siqin HE ; Xueying LIU ; Xiaotong YANG ; Tao GONG ; Yuan HUANG ; Huile GAO
Acta Pharmaceutica Sinica B 2023;13(5):2176-2187
Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.
5.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.
6.Analysis of urinary calculi composition in Longnan, Gansu province
Chaoming LI ; Haixia LI ; Jinwei GONG ; Penghui LI ; Guoshuai NAI ; Yajun ZHANG ; Wenjuan LI ; Yujun GAO ; Shenglong ZHAO ; Baojun ZHANG ; Shuntao LAN ; Tao ZHAO ; Bin YAO ; Xueren XU
Journal of Modern Urology 2023;28(12):1038-1041
【Objective】 To analyze the composition of urinary calculi in Longnan, Gansu province, and the relationship between the composition and clinical characteristics of patients, so as to provide reference for the prevention and treatment of this disease. 【Methods】 The composition of 500 cases of urinary calculi hospitalized in our department during Apr. 2021 and Feb.2023 were analyzed using the infrared spectrum stone composition analyzer. The clinical characteristics of the patients were evaluated and analyzed. 【Results】 The male-to-female ration of patients was 2.70∶1. Most patients aged 21 to 60 years (437, 87.4%). Most cases were ureteral calculi (72.8%), followed by renal calculi (22.2%), and bladder calculi (5.0%). There were 166 cases of calcium oxalate calculi, 293 cases of calcium oxalate + carbonated apatite calculi, 24 cases of calcium oxalate + carbonated apatite + hydroxyl apatite calculi, 4 cases of calcium oxalate + calcium bicarbonate calculi, 7 cases of urate calculi, 6 cases of carbonated apatite + struvite calculi. Oxalate calculi were the most common in all age groups, and urate calculi were the most common in the 21 to 40 age group. Calcium oxalate calculi were most common in the ureter (127, 76.5%), significantly higher than in other sites (χ2=3.222, P=0.020). Calcium oxalate + calcium hydrogen phosphate calculi was the least common in the bladder, significantly different from the other parts (χ2=2.092, P=0.037). Magnesium ammonium phosphate hexahydrate and/or calcium carbonate or calcium oxalate calculi were the most common in the kidney (50.0%), significantly different from the other parts (χ2=9.448, P=0.007). 【Conclusion】 In Longnan area, the incidence of urinary calculi is significantly higher in male than in female. Ureteral calculi are mainly composed of calcium oxalate + carbonated apatite and calcium oxalate. According to different risk factors, individual prevention programs should be developed.
7.Effects of personalized rehabilitation exercise program customized under cardiopulmonary exercise test on cardiac function and prognosis of patients with chronic heart failure
Huizhi WU ; Haixia YU ; Yujun GAO ; Jingxia ZHOU ; Yishu ZHAO
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2023;30(5):551-556
Objective To evaluate the impact of customized rehabilitation exercise plans based on the results of cardiopulmonary exercise test(CPET)on cardiac function and prognosis in patients with chronic heart failure(CHF).Methods A total of 52 CHF patients admitted to Chengde Central Hospital from February 2020 to September 2021 were selected as the study subjects,and the patients were divided into observation group and control group according to the principle of randomized controlled study,with 26 cases in each group.The control group received rehabilitation treatment excluding exercise.The observation group was given routine rehabilitation treatment and high-intensity rehabilitation exercise plans based on CPET guidance.Above anaerobic threshold Δ50%power was exercise intensity,exercise time was 30 minutes/day,4 days/week,and intervention period was 12 weeks.Before and 12 weeks after intervention,CPET functional indicators,serum brain natriuretic peptide(BNP),left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),and 6-minute walking distance(6MWD)were measured.The Minnesota CHF quality of life questionnaire(LiHFe)was used to evaluate patient's quality of life,readmission rate and cardiogenic mortality within 1 year of follow-up,and univariate and multivariate Logistic regression analysis was used to analyze factors affecting readmission of CHF patients.Results ① Cardiopulmonary function indicators:there was no statistically significant difference in the anaerobic threshold,peak oxygen uptake,and peak oxygen pulse of CPET functional indicators before and after intervention in the control group,after intervention,the CPET functional indicators in the observation group were significantly higher than those before intervention,and the above indexes in the observation group were significantly higher than those of the control group[anaerobic threshold(mL·min-1·kg-1):10.77±1.40 vs.9.59±1.11,anaerobic threshold(%ped):78.95±11.39 vs.70.09±6.48,peak oxygen uptake(mL·min-1·kg-1):15.63±1.36 vs.14.27±1.72,peak oxygen uptake(%ped):72.42±6.91 vs.63.41±7.31,peak oxygen pulse(mL/order):11.38±1.29 vs.9.05±1.64,peak oxygen pulse(%ped):90.23±10.16 vs.80.53±6.73,all P<0.05].②Serum indicators,cardiac function indicators,exercise ability indicators,and quality of life evaluation:there was no statistically significant difference in serum indicators BNP,cardiac function indicators LVEDD,LVEF,exercise ability indicators 6MWD,and quality of life LiHFe scores between the two groups before intervention.After intervention,BNP and LiHFe scores were significantly reduced compared with before intervention,while LVEF and 6MWD were both increased compared with before intervention,and the changes of the above indexes in the observation group were more significant than those in the control group[BNP(ng/L):313.25±77.91 vs.445.89±110.67,LVEF:0.41±0.08 vs.0.37±0.06,6MWD(m):495.62±91.35 vs.416.04±65.29,LiHFe score:23.27±6.02 vs.29.50±4.61,all P<0.05].③ Prognostic follow-up:the readmission rate within 1 year in the observation group was significantly lower than that in the control group(23.08%vs.53.85%),and there was no statistically significant difference in the mortality rate of cardiogenic diseases between the two groups.④Logistic univariate analysis showed that hyperlipidemia,New York Heart Association(NYHA)grading,BNP,and rehabilitation exercise were factors that affect the prognosis of CHF patients[odds ratio(OR)and 95%confidence interval(95%CI)were 0.098(0.019-0.494),0.069(0.016-0.294),1.018(1.007-1.029),and 3.889(1.178-12.841),respectively,all P<0.05].Multivariate analysis showed that after adjusting for other factors,hyperlipidemia,NYHA grading,and BNP were risk factors affecting the prognosis of CHF patients(OR and 95%CI were 0.068(0.007-0.687),0.048(0.005-0.415),1.016(1.002-1.030),respectively,with P<0.05],the use of rehabilitation exercise therapy was a protective factor affecting the prognosis of CHF patients[OR and 95%CI were 11.179(1.135-10.124),P<0.05].Receiver operator characteristic curve(ROC curve)analysis showed that hyperlipidemia,NYHA grading,BNP,rehabilitation exercise therapy,and combined testing all had predictive value for the patient's prognosis(all P<0.05),and the prediction value of joint detection was the highest,with the area under the ROC curve(AUC)=0.984 and P = 0.000.Conclusion Developing a high-intensity individualized cardiac exercise rehabilitation plan under the guidance of CPET can help improve the cardiopulmonary function,cardiac function,and quality of life of CHF patients,which is of great benefit for improving the long-term prognosis of CHF patients and has high safety.
8.Clinical characteristics and prognosis of pregnancy complicated with pheochromocytoma/paraganglioma
Yun LI ; Na LI ; Ning GUO ; Longmin LI ; Haichun LIU ; Hongbo GAO ; Xiaoyong ZHANG ; Yujun SHAO
Clinical Medicine of China 2022;38(1):24-29
Pheochromocytoma/paraganglioma is an adrenal tumor that secrets catecholamines and is extremely rare in pregnant women. Its clinical presentation is lack of specificity, and the combination of low prevalence and nonspecific clinical presentation makes diagnosis and treatment difficult. In this study, the clinical data and prognosis of 5 pregnant patients with pheochromocytoma/paraganglioma were analyzed. It was found that hypertension first occurred in 4 patients during pregnancy, and the clinical manifestations of each case were different. Surgical treatment is the first choice in the treatment, patients who cannot operate can choose radionuclide therapy, chemotherapy and targeted therapy. Through follow-up, they all showed recurrence and metastasis at different times. Among them, the patients who continued to be pregnant to the middle and late stages of surgical treatment progressed rapidly, and there were multiple bone metastases throughout the body in a short period of time, and two cases died in a short period of time. Therefore, effective diagnosis, individualized treatment and lifelong follow-up are particularly important.
9.Compliance of sepsis hour-1 bundle strategy for patients with septic shock in emergency department
Liang XU ; Zhiwei GAO ; Weiqin WU ; Yadong YU ; Weijun GUO ; Qi LI ; Changming ZHAO ; Yujun CHEN ; Siwei WANG ; Hongmei ZHAO ; Hong SUN ; Jinsong ZHANG
Chinese Journal of General Practitioners 2022;21(1):42-47
Objective:To investigate the implementation status of sepsis hour-1 bundle strategy for patients with septic shock in emergency department.Methods:A total of 116 septic shock patients admitted to the emergency department from January 2020 to December 2020 were included in this prospective study, and the implementation of sepsis bundles and the clinical outcomes of patients were recorded.Results:Among 116 patients, 20 cases (17.2%) had lactic acid monitored within 1 h, 20 cases (17.2%) had blood culture before antibiotics, 82 cases (70.1%) received broad-spectrum antibiotics, 16 cases (13.8%) received fluid resuscitation ≥30 ml/kg, and 57 cases (49.1%) received vasoactive drugs during resuscitation. Finally, the sepsis hour-1 bundle strategy was fully implemented only in 13 cases (11.2%). Compared with the group with incomplete implementation of sepsis hour-1 bundle strategy, the volume of fluid recovery in the group with full implementation was significantly increased [33.7 (30.0,37.5) vs. 8.9(7.3,10.8) ml/kg, Z=-4.78, P<0.001], mean artery blood pressure significantly increased [70.0 (70.0,76.7) vs. 67.7 (61.7,76.7)mmHg(1 mmHg=0.133 kPa) , Z=-2.00, P<0.001], and lactic acid significantly decreased [3.0 (2.0,3.2) vs. 4.4 (3.7,7.2) mmol/L, Z=-2.76, P=0.006]. However, there were no significant differences in ICU mortality, in-hospital mortality and 28-day mortality between the two groups ( P>0.05). Conclusions:Septic shock patients in emergency department have poor compliance with the implementation of sepsis hour-1 bundle strategy, and relevant management training should be strengthened.
10.Preliminary experience of flexible vacuum-assisted ureteral access sheath(FV-UAS) in retrograde intrarenal lithotripsy
Yujun CHEN ; Renrui KUANG ; Liang GAO ; Liangliang ZHENG ; Longlong KE ; Jie CHEN
Chinese Journal of Urology 2022;43(6):447-450
Objective:Objectives To introduce the preliminary experience of flexible vacuum-assisted ureteral access sheath(FV-UAS) in the treatment of upper urinary calculi in retrograde intrarenal lithotripsy(RIRS).Methods:The clinical data of 11 patients with upper urinary calculi who were treated in Jiangxi Provincial People's Hospital from August to September 2021 were analyzed retrospectively. There were 6 males and 5 females, with the mean age of 48 years (32-72 years), the mean size of stone of 15.5 mm (11-20mm), and the mean stone volume of 1 958 mm3 (1 108-4 036 mm3), including 1 case with upper ureteral calculi, 10 cases with renal calculi, and 2 cases with calculi in multiple renal calyces. Ureteral stents were placed in 2 cases preoperatively. There were 2 cases of grade Ⅱ hydronephrosis according to Grignon classification. All patients were treated by retrograde intrarenal lithotripsy, and the FV-UAS(F12/14) was used during the operation. FV-UAS can be passively bent(>90°) with the bending of the flexible ureteroscopy(f-URS), and connect vacuum suction devices. The method of placing the FV-UAS during the operation was the same as traditional ureteral access sheath. The FV-UAS should be as close to the target stone as possible by the f-URS during the operation. F6 ureteral stent was routinely indwelled for 2-4 weeks. The operation time, postoperative complications, and stone volume clearance rate were summarized and analyzed, and stone volume clearance rate was calculated as(1-residual stone volume/preoperative stone volume)×100%. The stone volume was obtained by CT 3-D reconstruction preoperatively and first day postoperatively.Results:All patients underwent RIRS successfully at the first stage, with the usage of FV-UAS(F12/14)during the operation. The mean operation time was 57.1 minutes(34-90 minutes), and the mean stone volume clearance rate was 98.9%(94.8%-100.0%)on the first day postoperatively. Seven cases reached 100.0% stone-free rate, and 4 cases presented residual calculi. The mean hemoglobin drop was 0.8 g/L, and 1 case presented vomiting without fever on the first day postoperatively. For the 4 cases with residual calculi, no residual stone was found by B-ultrasound when the ureteral stent was removed.Conclusions:Our preliminary study found that it is feasible and safe to use FV-UAS in RIRS, which can follow the f-URS to extend into the renal pelvis and renal calyces. Vacuum-assist can increase the probability of stone-free.

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