1.Protection of Ndrg2 deficiency on renal ischemia-reperfusion injury via activating PINK1/Parkin-mediated mitophagy
Min LIU ; Jianwen CHEN ; Miao SUN ; Lixia ZHANG ; Yao YU ; Weidong MI ; Yulong MA ; Guyan WANG
Chinese Medical Journal 2024;137(21):2603-2614
Background::Renal ischemia-reperfusion (R-I/R) injury is the most prevalent cause of acute kidney injury, with high mortality and poor prognosis. However, the underlying pathological mechanisms are not yet fully understood. Therefore, this study aimed to investigate the role of N-myc downstream-regulated gene 2 ( Ndrg2) in R-I/R injury. Methods::We examined the expression of Ndrg2 in the kidney under normal physiological conditions and after R-I/R injury by immunofluorescence staining, real-time polymerase chain reaction, and western blotting. We then detected R-I/R injury in Ndrg2-deficient ( Ndrg2-/-) mice and wild type ( Ndrg2+/+) littermates in vivo, and detected oxygen and glucose deprivation and reperfusion (OGD-R) injury in HK-2 cells. We further conducted transcriptomic sequencing to investigate the role of Ndrg2 in R-I/R injury and detected levels of oxidative stress and mitochondrial damage by dihydroethidium staining, biochemical assays, and western blot. Finally, we measured the levels of mitophagy in Ndrg2+/+ and Ndrg2-/- mice after R-I/R injury or HK-2 cells in OGD-R injury. Results::Ndrg2 was primarily expressed in renal proximal tubules and its expression was significantly decreased 24 h after R-I/R injury. Ndrg2-/- mice exhibited significantly attenuated R-I/R injury compared to Ndrg2+/+ mice. Transcriptomics profiling showed that Ndrg2 deficiency induced perturbations of multiple signaling pathways, downregulated inflammatory responses and oxidative stress, and increased autophagy following R-I/R injury. Further studies revealed that Ndrg2 deficiency reduced oxidative stress and mitochondrial damage. Notably, Ndrg2 deficiency significantly activated phosphatase and tensin homologue on chromosome ten-induced putative kinase 1 (PINK1)/Parkin-mediated mitophagy. The downregulation of NDRG2 expression significantly increased cell viability after OGD-R injury, increased the expression of heme oxygenase-1, decreased the expression of nicotinamide adenine dinucleotide phosphate oxidase 4, and increased the expression of the PINK1/Parkin pathway. Conclusion::Ndrg2 deficiency might become a therapy target for R-I/R injury by decreasing oxidative stress, maintaining mitochondrial homeostasis, and activating PINK1/Parkin-mediated mitophagy.
2.Study on Tongue Image Characteristics of TCM Symptoms in Patients with Different Fatigue Degree
Fangfang XIE ; Chaoqun XIE ; Jianwen MA ; Hongyu YUE ; Ruiqi XU ; Xiaojuan HU ; Fei YAO ; Jiatuo XU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(11):158-165
Objective To investigate the characteristics and rules of tongue image in patients with chronic fatigue syndrome(CFS)with different fatigue degree.Methods Totally 917 patients with severe chronic fatigue syndrome(severe CFS group),351 patients with mild chronic fatigue syndrome(mild CFS group)and 1216 healthy controls(healthy control group)were enrolled in the physical examination center of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine.The tongue image data of subjects in the three groups were collected using TFDA-1 digital tongue and face diagnostic instrument,and the color space indexes of RGB,HSI,Lab and YCrCb were used to analyze the tongue image differences of CFS people with different fatigue degrees and the tongue image features of CFS patients with liver-qi stagnation syndrome,damp-heat stasis syndrome and spleen deficiency syndrome.Results Compared with the healthy control group,the tongue image indexes TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-H,TC-I,TC-L and TC-Y increased in the severe CFS group;TB-S,TB-a,TC-S,TC-a,TC-Cr decreased(P<0.05).TB-R,TB-G,TB-B,TB-I,TB-L,TB-Y,TC-R,TC-G,TC-B,TC-I,TC-L and TC-Y increased in severe CFS group compared with mild CFS group.TB-H and TB-b increased in mild CFS group compared with healthy control group.The comparison of syndromes in severe CFS group showed that TB-a,TB-Cr,TC-S,TC-a,TC-Cr and TB-S increased in liver-qi stagnation syndrome compared to damp-heat stasis syndrome;TB-G,TB-B,TB-I,TB-L,TB-Y,TB-b,TB-Cb,TC-G,TC-B,TC-H,TC-I,TC-L,TC-Y and perAll decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-Cr,TB-CON,TB-ENT,TB-MEAN,TC-a,TC-Cr,TC-CON,TC-ENT,TC-MEAN increased in liver-qi stagnation syndrome;TB-ASM,TC-S and TC-ASM decreased(P<0.05).Compared with spleen deficiency syndrome,TB-a,TB-b,TB-Cr,TB-Cb,TB-CON,TB-ENT,TB-MEAN,TC-G,TC-B,TC-H,TC-I,TC-L,TC-a,TC-Y,TC-Cr,TC-CON,TC-ENT,TC-MEAN,perAll increased;TB-ASM,TC-S and TC-ASM decreased(P<0.05).The comparison of mild CFS syndrome showed that there was no statistical significance between liver-qi stagnation syndrome and spleen deficiency syndrome(P>0.05).TB-Cr,TC-a,TC-Cr and perAll increased and TC-S decreased in damp-heat stasis syndrome compared with spleen deficiency syndrome(P<0.05).TB-S,TB-a,TB-Cr,TC-S,TC-a,TC-Cr increased,and TB-G,TB-B,TB-I,TB-Cb,TB-b,TC-b and TC-Cb decreased(P<0.05)in liver-qi stagnation syndrome compared with damp-heat syndrome.The distribution trend of TC-S was as follows:dampness-heat syndrome
3.Meta-analysis on the effects of exercise training-based respiratory rehabilitation therapy in pneumoconiosis patients
Jianwen GE ; Ting XUE ; Zhimin LI ; Xingxing MA ; Yan DONG ; Wenjuan DAI ; Dongyan LI
China Occupational Medicine 2024;51(3):285-291
Objective To comprehensively analyze the effectiveness of exercise training-based respiratory rehabilitation therapy on patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). MethodsLiterature on randomized controlled trials of exercise training-based respiratory rehabilitation therapy for pneumoconiosis patients published from the establishment of the database to July 2023 was retrieved from academic systems such as the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database, and China Biology Medicine using bibliometrics method. The RevMan 5.4 software was used for meta-analysis of the selected literatures. Subgroup analysis was conducted to explore the source of study heterogeneity. The funnel plot method was used to test publication bias. Results A total of 55 articles were included, involving 2 436 pneumoconiosis patients in the experimental group and 2 405 pneumoconiosis patients in the control group. The result of random or fixed effect model showed that the six minutes walking distance, the total score of Short from Health Survey-36, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, arterial partial pressure of oxygen of pneumoconiosis patients increased after respiratory rehabilitation therapy (all P<0.05), while the total score of the St. George's Respiratory Questionnaire and arterial partial pressure of carbon dioxide decreased compared with the conventional treatment (all P<0.05). The result of subgroup analysis showed that the total score of the St. George's Respiratory Questionnaire, FEV1, and the index of arterial partial pressure of oxygen of pneumoconiosis patients was better in the rehabilitation treatment for ≥six months compared with those
4.Analysis of the efficacy of allogeneic hematopoietic stem cell transplantation on 9 children with Epstein-Barr virus-positive lymphoproliferative diseases
Jianwen ZHOU ; Yongyan HE ; Ping MA ; Weifang ZHANG ; Yafeng WANG ; Wei LIU ; Qiang ZHOU ; Yanna MAO
Chinese Journal of Applied Clinical Pediatrics 2023;38(12):932-936
Objective:To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on the childhood Epstein-Barr virus(EBV)-positive lymphoproliferative diseases(EBV + LPD). Methods:The clinical features, treatment course, and prognosis of 9 children with EBV + LPD who underwent allo-HSCT in Children′s Hospital Affiliated to Zhengzhou University from July 2019 to July 2022 were analyzed retrospectively. Results:All the 9 children underwent histopathological examination, including 6 patients with EBV-positive T-cell lymphoproliferative disease (EBV + T-LPD), 1 with pulmonary lymphomatoid granuloma, and 2 with systemic EBV-positive T-cell lymphoma.There were 6 males and 3 females, with the median age of 5.8 (1.5-13.0) years.At the initial diagnosis, plasma and peripheral EBV-DNA copy at the initial diagnosis was (5.67-865.00)×10 2/mL, and (5.13-1 250.00)×10 2/mL, respectively.The EBV-DNA load of cerebrospinal fluid increased to (5.18-291.00)×10 2/mL in 3 cases.The whole exon sequencing data showed no abnormality in 3 cases, pulmonary lymphomatoid granuloma with the IL2RG mutation in 1 case and EBV + T-LPD with a hemizygous mutation in the SH2D1A gene as the pathogenic mutation in 1 case.Pathogenic mutations were not detected in the remaining 4 cases.The course of disease before transplantation was 5.4(3.0-10.0) months.Disease status before transplantation was as follows: all 3 cases of lymphomas had partial regression; 2 cases of EBV + T-LPD had active disease; and 4 cases had no active disease.Among the donors, there were 5 cases of half-matched relatives, 2 cases of full-matched siblings and 2 cases of unrelated full-matched donors.The median number of mononuclear cells in peripheral blood and/or bone marrow hematopoietic stem cell was 6.60(3.64-12.18)×10 8/kg, while the median implantation time of neutrophils was 18(9-23) days.One month after the transfusion of hematopoietic stem cells, plasma EBV-DNA copy was negative in all cases, and peripheral EBV-DNA copy was negative in 7 cases.The copy number in the other 2 cases was 10 2/mL.At the 3-month evaluation, plasma and peripheral EBV-DNA copy were negative in all cases.In addition, 3 cases of lymphomas achieved radiographic complete remission, and 6 cases of EBV + T-LPD were inactive.All transplant-related complications were effectively controlled after medication.Following the median follow-up of 24 (11-42) months, all patients had disease-free survival.Serious impact on the quality of life due to graft versus host disease was not reported. Conclusions:allo-HSCT is an effective treatment of childhood EBV + LPD, which is able to control transplant-related complications.Children with EBV + LPD can achieve long-term disease-free survival through transplantation.
5.Individualized red-cell transfusion strategy for non-cardiac surgery in adults: a randomized controlled trial.
Ren LIAO ; Jin LIU ; Wei ZHANG ; Hong ZHENG ; Zhaoqiong ZHU ; Haorui SUN ; Zhangsheng YU ; Huiqun JIA ; Yanyuan SUN ; Li QIN ; Wenli YU ; Zhen LUO ; Yanqing CHEN ; Kexian ZHANG ; Lulu MA ; Hui YANG ; Hong WU ; Limin LIU ; Fang YUAN ; Hongwei XU ; Jianwen ZHANG ; Lei ZHANG ; Dexing LIU ; Han HUANG
Chinese Medical Journal 2023;136(23):2857-2866
BACKGROUND:
Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion.
METHODS:
Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test).
RESULTS:
We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies.
CONCLUSION:
The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT01597232.
Humans
;
Adult
;
Postoperative Complications
;
Erythrocyte Transfusion/adverse effects*
;
Blood Transfusion
;
Hospitals
;
Hemoglobins/analysis*
6.Expression of RUNX2/LAPTM5 in the Induction of MC3T3-e1 Mineralization and Its Possible Relationship with Autophagy
Lei XING ; Yanqin LI ; Wenhao LI ; Rong LIU ; Yuanming GENG ; Weiqun MA ; Yu QIAO ; Jianwen LI ; Yingtao LV ; Ying FANG ; Pingping XU
Tissue Engineering and Regenerative Medicine 2022;19(6):1223-1235
BACKGROUND:
The study aims to correlate osteogenesis with autophagy during the mineralization induction of MC3T3-e1 through exploring the expression of runt-related transcription factor 2 (RUNX2)/lysosomal-associated transmembrane protein 5 (LAMPT5).
METHODS:
The induction of mineralization in MC3T3-e1 was followed by detecting the expressions of osteogenesisrelated indexes such as RUNX2, alkaline phosphatase (ALP), osteocalcin (OCN), and LAPTM5 using RT-qPCR and Western blot from 0 to 14 days. Transmission electron microscope was utilised in visualizing the alterations of autophagosomes, which was followed by immunofluorescence detecting the subcellular localization of autophagy-related index sequestosome 1 (P62) and microtubule-associated protein 1 light 3 (LC3) protein and scrutinising the expression of P62 mRNA and P62 and LC3 proteins.
RESULTS:
Induction of MC3T3-e1 mineralization demonstrated an increased expression of osteogenesis-related indicators such as RUNX2, ALP, OCN, and LAPTM5 (p < 0.05), as evident from the results of RT-qPCR and Western blot. Meanwhile, the expression of autophagosomes increased one day after mineralization induction and then experienced a gradual decline, and enhanced expression of LC3 protein was noted on days 1–2 of mineralization induction but was then followed by a corresponding reduce. In contrast, a continuous increase was reported in the expression of P62 mRNA and protein, respectively (p < 0.05). Up- and down-regulating RUNX2/LAPTM5 expression alone confirmed the aforementioned results.
CONCLUSION
It was therefore proposed that RUNX2 may be responsible for an early increase and then a gradual decrease in LAPTM5-mediated autophagy through the regulation of its high expression. Meanwhile, increased LAPTM5 expression in osteogenic mineralization presumed that RUNX2/LAPTM5 promoted autophagy and osteogenic expression, which may play a bridging role in the regulation of autophagy and osteogenesis.
7.Expression of fructose bisphosphate aldolase A in bone marrow of patients with acute myeloid leukemia and its influence on prognosis
Ping MA ; Liang TIAN ; Lihuan SHI ; Jianwen ZHOU ; Yanna MAO ; Wei LIU ; Yongyan HE ; Silin GAN ; Hui SUN
Journal of Leukemia & Lymphoma 2022;31(11):664-668
Objective:To explore the expression of fructose bisphosphate aldolase A (ALDOA) in the bone marrow of patients with acute myeloid leukemia (AML) and the correlation with clinical features and prognosis.Methods:The bone marrow samples of 90 newly diagnosed AML (non-acute promyelocytic leukemia) patients and 18 allogeneic hematopoietic stem cell transplantation donors who were treated from January 2013 to December 2015 in the First Affiliated Hospital of Zhengzhou University and the Children's Hospital Affiliated to Zhengzhou University were collected. The relative expression level of ALDOA mRNA in bone marrow samples was detected by using real-time quantitative polymerase chain reaction (qRT-PCR). Clinical data of these patients were retrospectively analyzed, and the patients were divided into continuous complete remission (CR) group and refractory recurrent (RR) group according to the clinical response and follow-up results. The differences of the relative expression level of ALDOA mRNA between AML group and the normal control group, CR group and RR group were analyzed. Univariate and multivariate Cox regression risk model were used for analysis of factors influencing prognosis of AML patients.Results:The relative expression level of ALDOA mRNA in AML group was higher than that in normal control group [(5.71±0.44) vs. (1.10±0.08), t = 4.74, P<0.001]. The relative expression level of ALDOA mRNA in the RR group was higher than that in the CR group [(6.69±0.67) vs. (4.30±0.36) , t = 2.79, P < 0.001]. In addition, there were statistically significant differences in the proportion of patients with ALDOA mRNA high expression and those with ALDOA mRNA low expression stratified by the number of white blood cell, the proportion of bone marrow blasts and whether complete remission could be achieved or not after 1 course of induction therapy (all P < 0.05). Overall survival in patients with ALDOA high expression was worse than that in patients with ALDOA low expression ( χ2 = 5.59, P = 0.018). Multivariate analysis showed that white blood cell count, prognosis stratification, whether complete remission could be achieved or not after 1 course of induction therapy and ALDOA expression were the independent prognostic factors for the death of AML patients (all P < 0.05). Conclusions:ALDOA may play an important role in the development and progression of AML, and the expression level of ALDOA in the bone marrow can be used as an index for the prognosis assessment of AML patients and may be a potential therapeutic target for AML.
8.Investigation of contamination of SARS-CoV-2 in imported frozen seafood from a foreign cargo ship and risk factors for infection in stevedores in Qingdao
Jing JIA ; Qun YUAN ; Jianwen HUI ; Jiwei LIANG ; Xia WANG ; Huihui LIU ; Zhaoguo WANG ; Xiaoqi DAI ; Bi HAO ; Ruqin GAO ; Fachun JIANG ; Huilai MA
Chinese Journal of Epidemiology 2021;42(8):1360-1364
Objective:To investigate the contamination status of SARS-CoV-2 in imported frozen seafood from a Russia cargo ship in Qingdao and to analyze the risk factors for infection in local stevedores.Methods:The method of "two-stage, full coverage and mixed sampling" was used to collect the seafood packaging samples for the nucleic acid detection of SARS-CoV-2 by real-time fluorescent quantitative RT-PCR. A unified questionnaire was designed to investigate 71 stevedores in two shifts through telephone interview. The stevedores were divided into two groups, with 23 in the shit with two infections was group A and 48 in the shift without infection was group B. Software Epi Info7.2 was used to identify the risk factors for SARS-CoV-2 infections in the stevedores.Results:In the frozen seafood from a Russia cargo ship, the total positive rate of SARS-CoV-2 nucleic acid in the frozen seafood was 11.53% (106/919). The positive rate of SARS-CoV-2 nucleic acid in the frozen seafood unloaded by group A (14.29%,70/490) was significantly higher than that in the frozen seafood unloaded by group B (8.39%,36/429)( χ2=7.79, P=0.01) and the viral loads detected in the frozen seafood unloaded by group A were higher than those detected in the frozen seafood unloaded by group B. The scores of personal protection and behaviors in the stevedores in group A were significantly lower than those in group B ( P<0.05), and toilet use, smoking and improper hand washing before meals were the risk factors for the infection. Conclusions:The imported frozen seafood was contaminated by SARS-CoV-2 and the contamination distribution was uneven. Supervision and management of personal occupational protection and behaviors of workers engaged in imported frozen food transportation should be strengthened. It is suggested that a closed-loop monitoring and management system for the whole process of "fishing-transport- loading/unloading" should be established by marine fishery authority.
9.Safety and short-term outcomes of laparoscopic abdominoperineal resection with pelvic peritoneum closure for low rectal cancer
Leqi ZHOU ; Xialin YAN ; Bo FENG ; Hao SU ; Zirui HE ; Sen ZHANG ; Junjun MA ; Jing SUN ; Pei XUE ; Jianwen LI ; Aiguo LU ; Mingliang WANG ; Minhua ZHENG
Chinese Journal of Digestive Surgery 2019;18(8):768-772
Objective To investigate the safety and short-term outcomes of laparoscopic abdominoperineal resection with pelvic peritoneum closure (LARP-PPC) for low rectal cancer.Methods The retrospective cohort study was conducted.The clinicopathological data of 132 patients with low rectal cancer who were admitted to Ruijin Hospital of Shanghai JiaoTong University School of Medicine from January 2014 to December 2017 were collected.There were 81 males and 51 females,aged from 45 to 83 years,with an average age of 62 years.Among the 132 patients,60 undergoing LARP-PPC were allocated into LARP-PPC group,and 72 patients undergoing conventional LARP were allocated into LARP group.All the patients received standardized preoperative and postoperative treatments.Observation indicators:(1) surgical and postoperative conditions;(2) postoperative pathological examination;(3) postoperative complications.The measurement data with normal distribution were expressed as Mean±SD,and the t test was used for comparison between groups.The measurement data with skewed distribution were expressed as M (range),and the Mann-Whitney U test was used for comparison between groups.The count data were expressed as absolute numbers,and the chi-square test or the Fisher exact probability was used for comparison between groups.Mann-Whitney U test was used for comparison of ordinal data between groups.Results (1) Surgery and postoperative conditions:all the patients in the two groups underwent successful surgery without conversion to open surgery.The operation time,volume of intraoperative blood loss,time to first flatus,and time to first liquid intake of the LARP-PPC group were (163±45) minutes,168 mL(range,85-280 mL),2 days(range,1-5 days),3 days(range,2-6 days),versus (155±39) minutes,160 mL(range,100-305 mL),3 days(range,1-7 days),4 days(range,2-7 days) of the LARP group;there was no differencebetween the two group (t =1.113,Z =-1.623,-1.468,-0.321,P>0.05).The duration of postoperative hospital stay in the LARP-PPC group and the LARP group were 16 days (range,11-21 days) and 19 days (14-24 days),respectively,with a significant difference between the two groups (Z =-5.888,P<0.05)].In the LARP-PPC group,time of PPC was (13± 3) minutes.(2) Postoperative pathological examination:the length of specimen,the number of lymph node dissection,tumor diameter,cases with high-,middle-,and low-differentiated tumor in the LARP-PPC group was (18±4)cm,16±t5,(3.7±1.4)cm,10,34,16 in the LARP-PPC group,and (18±4)cm,16±5,(3.9±1.5) cm,13,41,18 in the LARP group,showing no significant difference between the two groups (t =0.779,0.390,0.703,Z=-0.267,P>0.05).(3) Postoperative complications:cases with perineal wound infection,delayed perineal wound healing,intestinal obstruction,and perineal hernia were 2,1,1,0 in the LARP-PPC group,and 12,10,8,6 in the LARP group,showing significant differences between the two groups (x2 =6.137,6.400,P<0.05).There were 2 and 4 patients with urinary tract infection in the LARP-PPC group and the LARP group,respectively,showing no significant difference between the two groups (P > 0.05).Conclusion LARP-PPC is safe and feasible for the treatment of low rectal cancer,which can significantly reduce postoperative perineal-related complications and consequently shorten postoperative hospital stay.
10.Preparation of Small Peptide AEYLR Modified Paclitaxel Nanostructured Lipid Carriers and Evaluation of Its Anti-tumor Effects
Cuiyan HAN ; Jianwen ZHOU ; Chang LIU ; Xiaoxing MA ; Cheng YUAN ; Yan DONG ; Shanshan JIN
China Pharmacy 2019;30(6):770-775
OBJECTIVE: To prepare Paclitaxel(PTX)nanostructured lipid carriers (NLC) modified by small peptide alanine-glutamic acid-tyrosine-leucine-arginine (AEYLR), and to evaluate its anti-tumor effect in vitro and in vivo. METHODS: NLC, PTX-NLC (P-NLC) and AEYLR modified P-NLC (A-P-NLC) were prepared by emulsion evaporation-low temperature solidification curing method. Its appearance, particle size, multi-dispersion index(PDI) and Zeta potential were characterized,encapsulation rate,drug loading and in vitro drug release were detected respectively. Using NCI-H1299 and S180 cells as objects, CCK-8 method was adopted to investigate inhibitory effects of free PTX, P-NLC and A-P-NLC (0.44-44.00 μg/mL, by PTX) to those cells. The half inhibition concentration (IC50) was calculated. Using S180 tumor-bearing mice as model animal, anti-tumor effects of free PTX, P-NLC and A-P-NLC (5 mg/kg, by PTX) were evaluated. RESULTS: P-NLC and A-P-NLC were round-like and dispersed evenly. The particle size, PDI and Zeta potential of A-P-NLC were (43.92±0.76) nm, 0.203±0.034 and (-19.77±1.16) mV, which were all increased to certain extent, compared with P-NLC. The encapsulation efficiency and drug loading of A-P-NLC were (95.71±0.68)% and(1.97±0.25)%, which were both decreased to certain extent, compared with P-NLC. The cumulative release rate of A-P-NLC was(35.17±2.08)% within 48 h, showing significant sustained-release effect compared with free PTX; the release of A-P-NLC was slower than P-NLC. Compared with free PTX and P-NLC, inhibitory rates of same concentration of A-P-NLC to NCI-H1299 cells and S180 cells were almost increased significantly, while IC50 values were all decreased significantly. There was no death in S180 tumor-bearing mice treated with A-P-NLC and the general condition was good; the volume of tumors was significantly reduced, the mass of tumors was significantly reduced, and the inhibition rate of tumors was significantly increased (P<0.05 or P<0.01). CONCLUSIONS: A-P-NLC has significantly sustained-release effects; its inhibitory rate to NCI-H1299 cells and S180 cells in vitro, and its inhibitory effects on S180 solid tumor in mice are all better than free PTX and P-NLC, while the toxicity is decreased to certain extent.

Result Analysis
Print
Save
E-mail