1.Effects of targeting modification on intracellular transportation of PEG-PCL micelles in human cervical cancer cells
Jinjin YANG ; Qinghua YU ; Lingbo YU ; Yadong ZHANG ; Dongqin LIANG ; Yuyu SUN ; Huiyun WANG ; Yanan CUI
China Pharmacy 2024;35(12):1431-1436
OBJECTIVE To study the effects of transferrin-targeting peptide T7 (7pep) on intracellular transportation of polyethylene glycol-polycaprolactone (PEG-PCL) micelles in human cervical cancer HeLa cells. METHODS Using coumarin-6 (C6) as fluorescent indicator probe, both coumarin-6 (C6)-loaded PEG-PCL (PEG-PCL-C6) micelles and 7pep-modified PEG- PCL (7pep-PEG-PCL-C6) micelles were prepared by film-dispersion method. The particle size, polydispersity index and appearance morphology were compared between two types of micelles; the real-time uptake of two types of micelles by HeLa cells was compared, and the colocalization of two types of micelles with early endosomes (EE), endocytic recycling compartments (ERC) and late endosomes (LE) after entry into the cells was observed. RESULTS The particle sizes of PEG-PCL-C6 and 7pep-PEG-PCL- C6 micelles were(75.0±2.3)and(82.0±1.5)nm; the polymer dispersity indexes were 0.17±0.20 and 0.17±0.32, respectively, with a regular spherical appearance. The colocalization results showed that entry speed and amount of 7pep-PEG-PCL-C6 micelles were significantly faster/more than those of PEG-PCL-C6 micelles. 7pep-PEG-PCL-C6 micelles entered EE faster than PEG-PCL-C6 micelles, while PEG-PCL-C6 micelles entered ERC at a faster rate than 7pep-PEG-PCL-C6 micelles, and both PEG-PCL-C6 micelles and 7pep-PEG-PCL-C6 micelles tended to accumulate gradually in LE; Pearson coefficient, signal overlap ratio, and colocalization ratio of 7pep-PEG-PCL-C6 micelles with LE were significantly lower 60 minutes after entering the cell than those 30 minutes after entering the cell (P<0.05 or P<0.01). CONCLUSIONS Targeting 7pep modification can increase the entry speed and amount of PEG-PCL-C6 micelles, and also alter their intracellular transportation behavior.
2.Quality evaluation of registration data of Shenzhen Type 1 Diabetes Alliance: based on the collaborative research platform network of China Type 1 Diabetes Alliance
Xueting LIU ; Haiyan LI ; Lingbo LYU ; Mingzheng LI ; Yan HUANG ; Shu LI ; Hongmei WU ; Qin ZHANG ; Chuanqi CHEN ; Liao SUN ; Zhiguang ZHOU ; Xia LI ; Dewen YAN
Journal of Chinese Physician 2022;24(7):1060-1066
Objective:To evaluate the data quality of Shenzhen Type 1 Diabetes Alliance (SZT1D), and to provide a basis for evaluation and improvement for the continuous improvement of data quality.Methods:From December 2018 to July 2021, 697 first-visit type 1 diabetes (T1DM) patients (including 501 in Shenzhen and 196 out-of-Shenzhen) and 120 re-visited T1DM patients (including 113 in Shenzhen and 7 out-of-Shenzhen) who were registered by SZT1D in collaborative research platform network of China Type 1 Diabetes Alliance (hereinafter referred to as China T1D). The data quality was evaluated from three dimensions: data completion, accuracy and revisit. The data completion degree was evaluated by the overall data completion degree and the key indicator completion degree; the data accuracy was evaluated by the probability of abnormal blood glucose value; the patient′s return visit was evaluated by the return visit rate.Results:The main characteristics of T1DM in SZT1D were young and middle-aged adults [age: (34.4±17.1)years] with thin body [BMI: (19.80±3.52)kg/m 2)], half of male and female patients [proportion of male: 52.4%(365/697)]; the main types of diagnosis were classical T1DM [65.22%(150/230)] and latent autoimmune diabetes in adults(LADA) [26.08%(60/230)], and the fasting blood glucose (FPG) [(10.93±6.98)mmol/L] and glycosylated hemoglobin (HbA 1c) [(10.63±3.01)%] were high. The average completion rate of the overall data of the first diagnosed patients in SZT1D was only 60% [(62.9±31.5)%]: the number of patients with overall data completion ≥80% in SZT1D was only 50.2%(350/697); the number of patients with overall data completion ≥80% in Shenzhen was less than that outside Shenzhen [44.3%(222/501) vs 65.3%(128/196), P<0.001]. The key indicators with better completion rate of first-visit were disease course [76.2%(531/697)], age of onset [75.8%(528/697)], family history of diabetes [74.9%(522/697)], etc., but none of them had a completion rate of more than 80%, and the diabetes self-management behavior assessment questionnaire and scale score were completely missing; the frequency of daily blood glucose monitoring [46.1%(231/501) vs 64.3%(126/196), P<0.001], current insulin regimen [44.3%(222/501) vs 63.3%(124/196), P<0.001], number of diabetic ketoacidosis (DKA) since the onset of the disease [45.7%(229/501) vs 64.8%(127/196), P<0.001] and the number of symptomatic hypoglycemia in the past 1 month [39.3%(197/501) vs 63.8%(125/196), P<0.001] were higher in Shenzhen than those reported outside Shenzhen. In addition, the probability of abnormal FPG and postprandial glucose (PPG) [5.2%(24/466); 3.8%(19/236)] were low. The revisit rate was not high [17.2%(120/697)], and the revisit rate in Shenzhen was higher than that outside Shenzhen [22.6%(113/501) vs 3.6%(7/196), P<0.001]. The first revisit rate was 16.2%(113/697) and the second revisit rate was seriously insufficient [1.0%(7/697)]. Conclusions:The data quality of T1DM patients recorded by SZT1D needs to be further improved. Improving the information interconnection between China-T1D and SZT1D, employing quality control personnel and building a systematic data quality evaluation analysis and feedback mechanism are methods to promote the comprehensive, accurate and efficient input of T1DM data and continuously improve the evaluation methods to improve the overall data quality.
3.Fluid-Structure Interaction Simulation of Multiple Overlapping Uncovered Stent Intervention in Aortic Dissection
Lingbo FENG ; Cuiru SUN ; Xiangchen DAI ; Haofei LIU
Journal of Medical Biomechanics 2021;36(5):E738-E746
Objective To propose a one-way fluid-structure interaction (FSI) method based on an idealized aortic dissection model, so as to analyze the hemodynamics and wall stress in the false lumen (FL) under the influence of multiple overlapping uncovered stents (MOUS). Methods Upon establishment of the numerical model, the models were divided into two categories according to whether the model involved FL perfused branch artery. The characteristics of hemodynamics and wall stress state in the post-operative scenarios were simulated under different surgical strategies. The wall stress state of the FL before and after thrombosis formation was also compared and analyzed. ResultsThe release process of the stents had little influence on wall stress of the FL. The high velocity and high wall shear stress (WSS) area in the FL could not be reduced by using the MOUS alone. If only the proximal entry tear was blocked with a covered stent-graft, the distal end would maintain a region of high flow rate and high WSS. The combination of covered stent-graft and MOUS would result in a region of low flow rate and low WSS, as well as reduced wall pressure and wall stress in the FL. Compared with the model with FL perfused branch arteries, the model without it was more likely to form a region of low flow rate and low WSS after surgery. However, blood pressure in the FL was relatively higher. The formation of thrombus in the FL could greatly reduce wall stress in the area covered by the thrombus. Conclusions The method proposed in this study can simultaneously investigate hemodynamics and wall stress characteristics of the FL, and provide support for studying mechanical mechanism of FL thrombolysis induced by MOUS and the post-operative aortic expansion.
4.Prevalence and characteristics of clinical Aeromonas isolates carrying mcr-3 gene
Yajie ZHAO ; Lingbo WANG ; Yishuai LIN ; Shixing LIU ; Yao SUN ; Tieli ZHOU ; Jianming CAO
Chinese Journal of Microbiology and Immunology 2020;40(9):697-702
Objective:To investigate the prevalence and characteristics of mcr genes in clinical isolates of Aeromonas spp. in our hospital, and provide reference for clinical analysis of the prevalence and expression of colistin resistance genes. Methods:Polymerase chain reaction (PCR) was used to detect mcr genes in 183 Aeromonas spp. strains. The minimum inhibitory concentrations (MICs) of colistin and polymyxin against mcr-positive Aeromonas spp. were detected by micro broth dilution method. Broth conjugation and filter mating conjugation were performed. Whole genome sequencing was used to analyze the genetic environment of mcr-3 gene in Aeromonas spp.. A recombinant Escherichia coli ( E. coli) DH5α-pGEM-T: : p mcr-3 strain was constructed to verify the expression of mcr-3 gene. Results:The positive rate of mcr-3 gene in 183 strains of Aeromonas spp. was 2.19% (4/183). No mcr-1 or mcr-2 gene was detected among these isolates. Antimicrobial susceptibility test showed that four mcr-3-carrying Aeromonas hydrophilia ( A. hydrophilia) strains were sensitive to colistin and polymyxin (MIC<2 μg/ml). Conjugation experiments indicated that mcr-3 gene could not be transferred between strains. Whole-genome sequencing analysis suggested that the mcr-3 genes carried by the A. hydrophilia isolates belonged to mcr-3.2 and mcr-3-like variants, and no adjacent transfer element was detected upstream and downstream. The recombinant E. coli DH5α-pGEM-T: : p mcr-3 strain was sensitive to colistin (MIC=2 μg/ml). Conclusions:The clinical isolates of A. hydrophilia in our hospital carried mcr-3 gene, but does not exhibit colistin resistance, and no evidence supported the transfer of mcr-3 gene for the time being.
5.Present situation and development direction of home healthcare
Wenjie YAN ; Lingbo SUN ; Jing LI
Chinese Journal of General Practitioners 2017;16(3):240-243
With the population ageing,increasing health needs and demands,changing family structure and the transformation of general hospital service model,home care as an important part of primary care,has been brought more and more attention.Home healthcare would relieve the pressure caused by increasing needs of elderly care and transformation of hospital functions,so it should have greater development in the future.This article reviews the present situation and the future development direction of home healthcare in China.
6.Analysis of clinical outcomes of different embryo stage biopsy in array comparative genomic hybridization based preimplantation genetic diagnosis and screening
Jiandong SHEN ; Wei WU ; Li SHU ; Lingbo CAI ; Jiazi XIE ; Long MA ; Xueping SUN ; Yugui CUI ; Jiayin LIU
Chinese Journal of Obstetrics and Gynecology 2017;52(12):828-834
Objective To evaluate the efficiency of the application of array comparative genomic hybridization (array-CGH) in preimplantation genetic diagnosis or screening (PGD/PGS), and compare the clinical outcomes of different stage embryo biopsy. Methods The outcomes of 381 PGD/PGS cycles referred in the First Affiliated Hospital of Nanjing Medical University from July 2011 to August 2015 were retrospectively analyzed. There were 320 PGD cycles with 156 cleavage-stage-biopsy cycles and 164 trophectoderm-biopsy cycles, 61 PGS cycles with 23 cleavage-stage-biopsy cycles and 38 trophectoderm-biopsy cycles.Chromosomal analysis was performed by array-CGH technology combined with whole genome amplification.Single embryo transfer was performed in all transfer cycles.Live birth rate was calculated as the main clinical outcomes. Results The embryo diagnosis rate of PGD/PGS by array-CGH were 96.9%-99.1%. In PGD biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were 50.0%(58/116) and 37.2%(58/156) in cleavage-stage-biopsy group, 67.5%(85/126) and 51.8%(85/164) in trophectoderm-biopsy group (both P<0.01). In PGS biopsy cycles, the live birth rate per embryo transfer cycle and live birth rate per embryo biopsy cycle were the same as 34.8%(8/23) in cleavage-stage-biopsy group, the same as 42.1%(16/38) in trophectoderm-biopsy group (both P>0.05). Conclusions High diagnosis rate and idea live birth rate are achieved in PGD/PGS cycles based on array-CGH technology.The live birth rate of trophectoderm-biopsy group is significantly higher than that of cleavage-stage-biopsy group in PGD cycles;the efficiency of trophectoderm-biopsy is better.
7.The value of MSCT in diagnosis of gastrointestinal vascular malformation
Lingbo DENG ; Xiaoguang LI ; Hao SUN ; Zhiwei WANG
Journal of Practical Radiology 2015;(6):942-946
Objective To explore the characteristics of gastrointestinal vascular malformation on contrast-enhanced multi-slice spiral computed tomography(MSCT)and assess the value of MSCT in diagnosis of gastrointestinal vascular malformation.Methods Forty-four patients with the final diagnosis of gastrointestinal vascular malformation were collected and analyzed retrospectively.We summarized the characteristics of contrast-enhanced MSCT in gastrointestinal vascular malformation and evaluated the value of MSCT in the diagnosis of gastrointestinal vascular malformation combined with image reconstructions such as MPR,MIP and VRT. Results Among 44 cases who received contrast-enhanced MSCT examination,18 cases were negative(40.9%),26 cases had positive signs(59.1%).In the 26 cases,1 case with diffuse lesions,1 case with multiple lesions,the others were local-type cases,in which 2 cases were showed contrast medium extravasations,6 cases were not only showed local mural hyper-intensification,but also multi-ple dilated small vessels around intestinal tract,10 cases were showed only local mural hyper-intensification,6 cases were showed only multiple dilated small vessels around intestinal tract.In the 24 local-type cases,lesions located at the stomach in 2 cases,the du-odenum 1 case,the jejunum 10 cases,the ileum 3 cases,the ileocecal junction 1 case,the colon 2 cases,the sigmoid colon-rectum 5 cases,respectively.Conclusion Contrast-enhanced MSCT can show the location,extent,patterns features of gastrointestinal vascu-lar malformation.It is helpful for detection and localization of the gastrointestinal vascular malformation with gastrointestinal bleed-ing.
8.Effect of prone position ventilation on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome concurrent with interstitial lung disease
Qingwen SUN ; Mangui ZHU ; Yin XI ; Yuheng YU ; Xuesong LIU ; Ling SANG ; Yonghao XU ; Sibei CHEN ; Lingbo NONG ; Weiqun HE ; Yuanda XU ; Yimin LI ; Xiaoqing LIU
Chinese Critical Care Medicine 2015;(10):785-790
ObjectiveTo explore the effect of prone position ventilation (PPV) on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome (ARDS) concurrent with interstitial lung disease (ILD). Methods The data of 36 severe ARDS patients admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University from February 2013 to January 2015, were retrospectively analyzed. They were then divided into two groups according to the presence of ILD or not. The changes in respiratory mechanics and oxygenation indexes were compared before and after PPV treatment in all the patients. Kaplan-Meier method was applied to draw the 60-day survival curves of both groups.Results There were 17 cases with ILD among these 36 severe ARDS patients.① No significant difference was found in baseline data between ILD group and non-ILD group.② Respiratory mechanics and oxygenation pre-PPV and post-PPV: compared with pre-PPV, oxygenation index (PaO2/FiO2, mmHg, 1 mmHg = 0.133 kPa) post-PPV was significantly increased in both groups [ILD group : 132.0 (93.5, 172.0) vs. 118.7 (92.0, 147.8); non-ILD group: 126.1 (100.9, 170.0) vs. 109.2 (89.0, 135.0), bothP< 0.05]. Compared with pre-PPV, positive end-expiratory pressure (PEEP, cmH2O,1 cmH2O = 0.098kPa) post-PPV was significantly higher in ILD group [10.0 (10.0, 12.0) vs. 10.0 (9.2, 12.0),P< 0.05], and respiratory rate (RR, times/min) was significantly lower in non-ILD group [24.5 (22.0, 27.0) vs. 25.5 (22.8, 28.0),P< 0.05]. The compliance of the respiratory system (Crs, mL/cmH2O) post-PPV in non-ILD group was significantly lower than that of the ILD group [19.7 (16.1, 28.6) vs. 23.0 (19.0, 29.7),P< 0.05].③ Respiratory mechanics and oxygenation pre-PPV and post-PPV in total: after all the PPV therapy, PaO2/FiO2 (mmHg) was significantly increased in non-ILD group [135.0 (86.0, 200.0) vs. 97.4 (69.2, 127.5), P< 0.05], PaO2/FiO2 after all the PPV therapy in non-ILD group was also higher than that in ILD group [135.0 (86.0, 200.0) vs. 78.7 (59.3, 114.9),P< 0.05]. No significant difference in Crs (mL/cmH2O) before PPV treatment was found between non-ILD and ILD groups [24.3 (15.9, 48.9) vs. 18.9 (12.7, 27.3),P> 0.05], and Crs was lower after PPV treatment in both groups, but without significant difference [non-ILD group: 22.7 (15.2, 27.1) vs. 24.3 (15.9, 48.9); ILD group: 16.2 (12.8, 25.6) vs. 18.9 (12.7, 27.3), bothP> 0.05].④ The 60-day mortality in ILD group was significantly higher than that in non-ILD group [88.2% (15/17) vs. 57.9% (11/19),P = 0.047). It was shown by Kaplan-Meier curves that 60-day survival patients in ILD group was significantly lower than those in non-ILD group (χ2 = 5.658,P = 0.017). Conclusions PPV can improve oxygenation in severe ARDS. Compared with non-ILD group, though the compliance of respiratory system in ILD group is increased during PPV, long-term effect is better in non-ILD group.
9.Effect of hyperbaric oxygen treatment on the expression of FasL and caspase-3 in renal tissue after renal ischemia reperfusion injury
Hui SUN ; Xinbing XU ; Lingbo MA ; Guangrong HU ; Ying DENG ; Xinchun WANG ; Fengping WANG
Chinese Journal of Nephrology 2012;(10):808-812
Objective To observe the effects of hyperbaric oxygen (HBO) on the expression of FasL mRNA and caspase-3 protein in renal tissue after renal ischemia-reperfusion injury (IRI) in order to elucidate the underlying mechanisms.Methods Rats were randomly divided into thrcc groups: sham group(n=8),IRI group(n=8) and IRI+HBO group(n=8).The IRI group and the IRI+HBO group recieved 45 minutes hibateral renal ischima and the IRI +HBO group received additional HBO therapy at the 1st,24th and 48th hour after ischemia.The kidneys were removed at the end of HBO therapy.Malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured to determine the extent of oxidative stress.The expression of FasL mRNA and caspase-3 protein was detected by quantitative real-time PCR and immunohistochemical staining in renal tissue respectively.Results Compared with the sham group,MDA level increased markedly and SOD activity decreased markedly after ischemia.After HBO treatment,MDA level decreased and SOD activity increased significantly (P <0.05).In IRI group,the expression of FasL mRNA and caspase-3 protein were higher than those in the sham group (P<0.01),which were reduced significantly by HBO treatment (P<0.01).Conclusion The expression of FasL mRNA and caspase-3 protein increases along with the lasting of reperfusion and HBO exhibites protection against cell apoptosis through improving the antioxidant-oxidant balance and reducing IRI in acute stage of IRI.
10.Clinical application of extracorporeal membrane oxygenation circuit in place of cardiopulmonary bypass
Yan LI ; Wen ZENG ; Lingbo SUN ; Jie HAN ; Chunlei XU ; Haibo ZHANG ; Jiangang WANG ; Feng GAO ; Yixin JIA ; Xu MENG
Clinical Medicine of China 2008;24(5):478-480
Objective To summarize the clinical experiences in setting up cardiopulmonary bypass(CPB)using extracorporeal membrane oxygenation(ECMO)circuit and turning CPB to ECMO after open heart operations in 16 cases.Methods In the group of 16 cases,the annulations were via femoral vessels:by Medtronic ECMO machine and membrane oxygenator was used in all patients.All patients accepted A-V bypass.Results CPB was running smoothly during the operations,and converted to ECMO after the surgeries without complications,and the rate of ECMO withdraw was 93.75%.Mortality was 18.5%,and 81.25%of patients were discharged.Conclusion ECMO is an effective device for cardio and pulmonary support.Many patients with severe cardiac diseases and marginal cardiac function will need mechanical support after surgery.For these patients,setting up CPB using ECMO circuit during the operation and converting it to ECMO after surgery can prevent patients from additional exposure to a standard CPB circuitry.It helps decrease the inflammatory response,avoid dilution of patient's volume of cells and factors,and reduce expenses.

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