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.Comparison of the effectiveness and safety profile of centrifugal and membrane plasma separation in artificial liver therapy with a dual plasma molecular adsorption system
Yuan LI ; Xiaolian LU ; Wancang XU ; Fang LI ; Xingyan MO ; Xiaoqin LAN ; Ling ZHOU ; Miaoxia LIU ; Junwei LIU ; Jinjun CHEN ; Beiling LI
Chinese Journal of Hepatology 2024;32(12):1109-1115
Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.
3.Comparison of the effectiveness and safety profile of centrifugal and membrane plasma separation in artificial liver therapy with a dual plasma molecular adsorption system
Yuan LI ; Xiaolian LU ; Wancang XU ; Fang LI ; Xingyan MO ; Xiaoqin LAN ; Ling ZHOU ; Miaoxia LIU ; Junwei LIU ; Jinjun CHEN ; Beiling LI
Chinese Journal of Hepatology 2024;32(12):1109-1115
Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.
4.Fluorescent antibiotics for real-time tracking of pathogenic bacteria
Lu MIAO ; Weiwei LIU ; Qinglong QIAO ; Xiaolian LI ; Zhaochao XU
Journal of Pharmaceutical Analysis 2020;10(5):444-451
The harm of pathogenic bacteria to humans has promoted extensive research on physiological processes of pathogens, such as the mechanism of bacterial infection, antibiotic mode of action, and bacterial antimicrobial resistance. Most of these processes can be better investigated by timely tracking of fluorophore-derived antibiotics in living cells. In this paper, we will review the recent development of fluorescent antibiotics featuring the conjugation with various fluorophores, and focus on their applica-tions in fluorescent imaging and real-time detection for various physiological processes of bacteria in vivo.
5. Effect of endoscopic sinus surgery on postoperative cognitive performance, quality of life and psychological status in patients with sinusitis and nasal polyps
Chinese Journal of Primary Medicine and Pharmacy 2019;26(15):1822-1825
Objective:
To explore the influence of endoscopic sinus surgery on postoperative cognitive performance, quality of life and psychological status of patients with sinusitis and nasal polyps.
Methods:
From January 2017 to January 2018, 300 patients with sinusitis and nasal polyps who underwent endoscopic sinus surgery in the Fifth Hospital of Shaoxing were selected.The quality of life, psychological status and cognitive performance of patients before and after surgery were compared.
Results:
After operation, 190 cases were cured, 90 cases were effective, and 20 cases were ineffective.The total effective rate was 93.33% (280/300 cases). After operation, the patients′ nasal endoscopy score was (3.23±0.34) points, which was significantly lower than before operation [(8.53±1.63)points] (
6.Third generation dual-source CT in early differential diagnosis of intracranial hemorrhage and iodinated contrast medium after endovascular treatment of acute ischemic stroke patients
Fang WU ; Xiangying DU ; Miao ZHANG ; Qi YANG ; Xiaolian ZHU ; Jie LU
Chinese Journal of Medical Imaging Technology 2018;34(5):770-774
Objective To investigate the value of third generation dual-source CT in early differential diagnosis of intracranial hemorrhage and iodinated contrast medium after endovascular treatment of acute ischemic stroke (AIS).Methods Totally 78 patients with AIS underwent endovascular treatment were prospectively enrolled.Dual-energy CT (DECT) examination (80 kV/Sn150 kV) of the head was performed after treatment with a third generation dual-source CT scanner.Iodine overlay maps and virtual non-contrast images were post-processed.Taking conventional brain CT images obtained 24 48 h after AIS attack as references,the accuracy,sensitivity,specificity,positive predictive value (PPV) and negative predictive value (NPV) of DECT for identifying hemorrhage were computed respectively.Results Totally 31 patients with 53 foci of intracranial hyper-attenuation were finally enrolled.Among 53 foci,26 were correctly diagnosed as hemorrhage by DECT,23 were correctly diagnosed as iodinated contrast medium,while 1 calcification was misdiagnosed as hemorrhage combined with iodinated contrast medium,3 were misdiagnosed as contrast medium which showed delayed hemorrhagic transformation.The sensitivity,specificity and accuracy of DECT was 89.66% (26/29),95.83% (23/24) and 92.45% (49/53),PPV and NPV was 96.30% (26/27) and 88.46% (23/26),respectively.Conclusion The third generation dual-source CT is available in early and accurate diagnosis of hemorrhagic transformation after endovascular treatment of AIS,which can help clinicians to adjust the subsequent treatment strategies in time.
7.Literature Analysis of Pediatric Drug-induced Liver Injury in China from 2007 to 2016
Xin ZHENG ; Xiongcai LU ; Xiaolian QIN ; Guanlin LI ; Jiyi WANG ; Fu LIU
China Pharmacy 2017;28(32):4507-4510
OBJECTIVE:To investigate the characteristics of pediatric drug-induced liver injury (DILI) in China,and to provide reference for reducing ADR.METHODS:Using"liver injury liver damage hepatotoxicity hepatitis liver disease""drug induced children" as keywords,related domestic literatures were retrieved from CNKI and Wanfang database during 2007-2016,clinical information of DILI children in literatures were recorded in detail and analyzed comprehensively.RESULTS:A total of 363 literatures were retrieved,including 13 effective literatures and 665 children in total.There were 424 boys (63.76%)and 241 girls (36.24%),with ratio of 1.76 ∶ 1.The youngest child was 1 month old,the oldest child was 14 years old;the average age was 7.87 years,337 children aged more then 7 years old,accounting for 50.68%.Top 3 primary diseases were respiratory tract infection (40 cases,31.50%),hematologic diseases (29 cases,22.83%) and tumor (14 cases,11.02%).Top 3 pediatric DILI-inducing drug types were antibiotics (245 cases,34.41%),TCM (143 cases,20.08%) and antipyretic analgesics (113 cases,15.87%).DILI usually happened within 4 weeks (332 cases,82.18%).The most common clinical classification was hepatocellular type (382 cases,65.30%).The severity of liver injury was mainly mild and moderate (505 cases,86.32%),and 80 cases were severe (13.68%),including 31 cases of hepatic failure (5.30%).Clinical symptoms mainly manifested as anorexia,jaundice,nausea,vomiting,hypodynamia and abdominal discomfort.After drug withdreawd and treatment,96.54% of the patients were recovered or cured,and 4 cases died (0.60%).CONCLUSIONS:Under the premise of rational use of drugs,it is necessary to carry out medication education and supervision for antibiotics,TCM and antipyretic analgesics which mainly induce pediatric DILI,pay attention to allergic history and evaluate the progress of extrahepatic symptoms.When ADR occurred,the timely and drug withdrawal intervention are conducted to improve good prognosis.
9."Introduction to the Application of Acupoint Sticking Therapy in the ""Treating Disease before Its Onset"""
Xiaolian LU ; Jie YU ; Xiaofeng MO
Journal of Zhejiang Chinese Medical University 2016;40(3):213-214
Objective] To summarize the clinical key points of acupoint sticking therapy in the application of treating disease before its onset. [Method] From the treatment timing, treatment principle, acupoint selection to expound the academic perspective and clinical experience of our department in the application of acupoint sticking therapy by consulting the ancient literature and summarizing clinical practice. [Result] Through the correct selection of treatment timing for acupoint sticking therapy, which is mainly used in summer, secondly used in winter, and focusing on tonifying Yang-qi, and point selection by pattern identification, paying attention to the accumulation of curative effect, this therapy has good curative effect in the treating disease before its onset.[Conclusion] Nowadays, there are more and more sub-health people. Since acupoint sticking therapy has advantages of“easy, convenient, cheap, uesful”and safe, it is a good therapy to apply for treating disease before its onset.
10.The Handbook of Nosocomial Infections Management:Evaluation of the Use and Effect
Xiaolian LU ; Wei TANG ; Liang LI ; Sheng ZHANG ; Jie CHEN
Chinese Journal of Nosocomiology 2009;0(24):-
OBJECTIVE To promote the management of nosocomial infections continuous improvement in the clinical and medical technology department.METHODS According to the regulation of nosocomial infections management,a handbook of nosocomial infections management for clinical and medical technology department was designed,and the monitors of nosocomial infection could perform real time inspection and record according require of the handbook.The department of nosocomial infections management examined the monitoring work of clinical and medical technology department every month and summarized every year,and the results were internalized to the valuation of medical quality management.RESULTS After 3 years of the usage of the handbook,the capability of the monitor groups of nosocomial infection and the quality of the all monitoring items were significantly improved;the qualified rates were all above 96.30%.CONCLUSIONS The handbook of nosocomial infections management is useful to improve the quality of nosocomial infections management in the clinical and medical technology department.

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