1.Study on Preparation and Antitumor Activity of Adriamycin-loaded PLGA-PLL-PEG Nanoparticles
Wei LIU ; Xiaotong WANG ; Jianhua WANG
China Pharmacy 2017;28(16):2262-2265
OBJECTIVE:To prepare adriamycin-loaded PLGA-PLL-PEG nanoparticles,and study its antitumor activity. METH-ODS:PLGA-PLL-PEG with the polymerization of PLGA-PLL and activated polyethylene glycol was used as carrier for adriamy-cin,and adriamycin-loaded PLGA-PLL-PEG nanoparticles were prepared. The shape size,particle size distribution,adriamycin con-tent of nanoparticles were detected,drug loading and encapsulation efficiency were calculated. Cumulative release rate (Q) of nanoparticles and adriamycin within 144 h and its proliferation inhibition rate on breast cancer HeLa cells were compared,and half inhibitory rate (IC50) was calculated. RESULTS:Prepared adriamycin-loaded PLGA-PLL-PEG nanoparticles were regular circular with good dispersion and no adhesion. The average particle size was (136.7 ± 9.3) nm (n=5),average encapsulation efficiency was(76.67±8.63)%,average drug loading was(3.86±0.55)%(n=3). Q12 h of adriamycin had reached 100%;Q12 h of adriamy-cin-loaded PLGA-PLL-PEG nanoparticles was 52.9%,Q144 h was 81.2%. The inhibitory rate of adriamycin-loaded PLGA-PLL-PEG nanoparticles on HeLa cells increased slowly than adriamycin;IC50 were 1.844,0.345 μg/mL,respectively. CONCLUSIONS:Adri-amycin-loaded PLGA-PLL-PEG nanoparticles are prepared successfully,showing good sustained-release effect and more significant inhibitory effect than adriamycin.
2.Risk factors for acute kidney injury after Sun’ s procedure in patients with acute aortic dissection
Wei SHANG ; Min MA ; Caixia RUAN ; Wei ZHANG ; Nan LIU ; Xiaotong HOU ; Lizhong SUN
Chinese Journal of Thoracic and Cardiovascular Surgery 2016;32(7):407-410
Objective To analyze the independent risk factors associated with acute kidney injury(AKI)after Sun’s pro-cedure in the patients with acute aortic dissection .Methods Clinical data of 400 patients who underwent Sun ’ s procedure from February 2009 to August 2013 were collected.Data included preoperative GFR, Cleveland values, CPB time and fluid balance of 24 h intra and after operation were gathered .The patients were divided into the group of AKI and the group of non-AKI accounting to the changing of serum creatinine.Results AKI was occurred in 150(37.5%) patients.Hospital mortality in AKI group was significant higher than that in the non-AKI group(11.3% vs.2.4%, P<0.05).Univariable analysis re-vealed male, BWI, hypertension, preoperative MAP,WBC, eGFR, Cleveland value, cardiopulmonary bypass time, intra and postoperative fluid balance for 24 h have significant difference between 2 groups.Multivariate logistic regression analysis showed hypertension, Cleveland value, cardiopulmonary bypass time and fluid balance were independent risk factors for AKI .Conclu-sion AKI after acute aortic dissection was a severe complication .Hypertension, Cleveland value, cardiopulmonary time and fluid balance were associated with AKI.
3.The association of high sensitive C reactive protein with acute kidney injury in a type aortic dissection patients after cardiopulmonary surgery
Caixia RUAN ; Wei SHANG ; Xiaotong HOU ; Hong WANG ; Chenglong LI ; Yujie ZHOU
Chinese Journal of Thoracic and Cardiovascular Surgery 2014;30(12):741-744
Objective This study aims to analyze if high sensitivity C Reactive Protein (hs-CRP) was a independent risk factor of acute kidney injury(AKI) after A type aortic dissection surgery.Methods Clinical data of the 169 patients who underwent A type acute aortic dissection surgery from February 2009 to October 2010 were collected.Patients without preoperative detection of hs-CRP,patients with preoperative infection and patients diagnosed infection before AKI were excluded.Enrolled patients were divided into AKI group and non-AKI group,and according to using RRT or not,the patients were divided into RRT group and non-RRT group.All the factors were evaluated by means of univariate and multivariate logistic regression analysis to identify relative risk factors of AKI.Results AKI occurred in 95 cases(56.2%),Using RRT in 8 cases (4.7%).hsCRP is an independent risk factor of AKI(OR =0.975,95% CI 0.952-0.999,P =0.041).hs-CRP and aortic cross clamping time were the independent risk factors of using RRT,The in-hospital mortality was significant difference between RRT group and non-RRT group (P < 0.05).The area under the ROC curve of hs-CRP on RRT diagnosis was 0.733,95% CI 0.570-0.896,P =0.026.The sensitivity of CRP > 30.42 mg/L warning AKI need RRT was 87.5%,the specificity was 53.4%.Conclusion AKI after A type aortic dissection surgery was a severe complication and RRT associated with in-hospital mortality,hs-CRP was higher in acute aortic dissection patients.The level of hs-CRP and aortic cross clamping time were independent risk factors of AKI and RRT.
4.Effects of caveolin-1 scaffolding domain peptide on LPS-induced acute lung injury in mice
Ping WENG ; Xiaotong ZHANG ; Wei CHEN ; Wenfang TIAN ; Junliang CHEN ; Jiajia YUAN ; Xinjie CHEN ; Qingfeng PANG
Chinese Journal of Pathophysiology 2017;33(8):1475-1480
AIM: To investigate the effects of caveolin-1 (Cav-1) scaffolding domain peptide, cavtratin, on lipopolysaccharide (LPS)-induced mouse acute lung injury and heme oxygenase-1 (HO-1) activity.METHODS: Adult male BALB/c mice were randomly divided into 6 groups (n=8 to 10): control, Antennapedia internalization sequence (AP), LPS, LPS+hemin, LPS+ hemin+cavtratin and LPS+hemin+cavtratin+zinc protoporphyrin IX (ZnPP) groups.After LPS administration for 24 h, the lung pathological changes, the wet/dry weight (W/D) ratio of lung tissues, total cell number in bronchoalveolar lavage fluid and serum lactate dehydrogenase activity were measured.The co-localization of HO-1 and Cav-1 was displayed by immunofluorescence, and the HO-1 activity were detected.The mRNA expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, MCP-1 and iNOS was detected by real-time PCR.RESULTS: The mice in LPS+hemin+cavtratin group had the decreased interaction between HO-1 and Cav-1, and the increased HO-1 activity compare with LPS group (P<0.05).Compared with LPS group, the pulmonary damage was attenuated in LPS+hemin+cavtratin group, and the injury indexes, including W/D ratio, total cell number in bronchoalveolar lavage fluid and lactate dehydrogenase activity in the serum, and the mRNA expression of inflammatory cytokines all decreased (P<0.05).HO-1 activity inhibitor ZnPP abolished the above protective effect of cavtratin on the lung tissues with LPS-induced acute lung injury.CONCLUSION: Cavtratin has beneficial effects on the lung with LPS-induced acute injury by restoring the HO-1 activity.
5.Evaluation of efficacy and safety of ZD1839 as monotherapy in Chinese patients with advanced non-small cell lung cancer
Mengzhao WANG ; Longyun LI ; Shulan WANG ; Xiaotong ZHANG ; Wei ZHONG ; Li ZHANG ; Junrong LI
Chinese Journal of Internal Medicine 2008;47(4):291-295
Objective To report the outcome of gefitinib for Chinese patients with advanced nonsmall cell lung cancer(NSCLC) at Peking Union Medical College Hospital. Methods From Oct. 2002 to Apr. 2006,204 patients with advanced NSCLC received oral ZD1839(250 mg/d)treatment. The were 110(59.9%)men and 94(40.1%)women aged between 25 and 85 years. Thirty-two patients had squamous cell carcinoma, 125 adenocarcinoma, 30 bronchoalveolar carcinoma or adenocarcinoma with partial bronchoalveolar carcinoma, 6 adenosquamous carcinoma. and 11 unspecified. Twenty-six patients had no history of chemotherapy, 62 had no disease progression after chemotherapy, and 111 failed to prior one or more regimens. Median survival was calculated using the Kaplan-Meier method and a Cox regression analysis was used to detect differences in median survival between strata. Results The median survival of all patients and of patients failed to prior chemotherapy were 16.3 months(95% confidential interval CI, 14.5-18.2)and 12.5 months(95% CI 9.3-15.7). The rate of 1-year survival was 57%. The obiective tumor response rate and stable disease rate were 31.4% and 41.7% respectively.The median survival were significantly related with ECOG scores,pathology types,disease progression after chemotherapy,objective efficacy of gefitinib and changes of short-breathing. Among 26 patients with no prior chemotherapy,the median survival was not statistically significant compared with that of other patients. Among the enrolled patients,111 had disease progression and 62 had stable disease after prior chemotherapy, and their median survivals was statistically different. At the time of this analysis. 142 patients had disease progression,58 of whom withdrew from taking gefitinib,and 84 continued gefitinib therapy until death. The median survivals for these subgroups were not significantly different. Among 142 patients with disease progression, 40 received other systemic treatment, the median survival was statistically significant compared with that of other patients. Objective response was significantly related with age,smoking status,pathological type,change of short-breathing and rashes induced by gefitinib. Adverse events were generally mild(grade 1 and 2)and reversible. The most frequent adverse events were rash 72.6%(138/190)and diarrhea 33.7%(64/190).Conclusion Our studv suggests that treatment with gefitinib may be well tolerate and beneficial for some Chinese patients after failure of prior chemotherapy.
6.The efficacv and safety of pemetrexed as monotherapy for Chinese patients with advanced non-small cell lung cancer
Wei ZHONG ; Jing ZHAO ; Xiaotong ZHANG ; Li ZHANG ; Mengzhao WANG ; Longyun LI
Chinese Journal of Internal Medicine 2010;49(8):671-674
Objective To assess the outcome of pemetrexed as monotherapy for Chinese patients with advanced non-small cell lung cancer ( NSCLC) at the Peking Union Medical College Hospital.Methods From February 2006 to August 2009, 69 patients with advanced NSCLC, including 36 (52.2% ) men and 33 (47.8%) women, received pemetrexed monotherapy.Six patients had squamous cell carcinoma, 57 adenocarcinoma, 6 unspecified.Median survival (MS) and progress-free survival (PFS) were calculated using the Kaplan-Meier method.Results Adverse events (AEs) were generally mild (grade 1 and 2) and reversible. The most frequent AEs were gastrointestinal adverse events, skin rash, fever and fatigue. Total 5 cases with 3/4 grade AEs were reported, including fever, fatigue, rash, decreased platelets and elevated ALT/AST. The objective tumour response rate and stable disease rate were 10.1% (7/69) and 47.8% (33/69) respectively. Median PFS of all patients was 4.7 months (95% CI 3.0 -6.4) and mean overall survival was 14.7 months (95% CI 11.5 - 17.9).Conclusions Our study suggests that treatment with pemetrexed may be well-tolerated and beneficial for some Chinese patients after failure of prior chemotherapy. The rate of disease control is high and the frequency of 3/4 grade AEs is very low.
7.Prophylactic cerebrospinal fluid drainage reduces paraplegia after extensive thoracoabdominal aortic aneurysm repair
Rong WANG ; Wei SHANG ; Yipeng GE ; Nan LIU ; Xiaotong HOU ; Junming ZHU ; Lizhong SUN
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(2):77-80
Objective To evaluate the impact of cerebrospinal fluid drain(CSFD) on the incidence of acute spinal cord injury(SCI) following extensive TAAA repair.Methods From February 2009 to July 2016,153 patients underwent extensive TAAA repairs with a consistent strategy of normal thermia,non-circulatory bypass,sequential aortic cross clamping,aortic-lilac bypass,and intercostal artery reconstruction.The repairs were performed with preoperative CSFD (n =78) or without CSFD (n =75).In the former group,CSFD was inserted after the patient has been anaesthetized and continued for 72 hours after surgery.The target CSF pressure was 10 mmHg or less.Results The mean age of patients was (38 ± 10) years and 108 (70.6%) were male.There were 87 (53.8%) patients with previous aortic surgeries and 33 (22%) with Marfan syndrome.The two groups had similar risk factors for paraplegia.Aortic clamp time,operation time and number of reattached intercostal arteries were similar in both groups.In-hospital mortality rates were 1.3% (one patient) and 6.7% (five patients) for CSFD and the group without CSFD,respectively (P =0.086).Ten patients (13.3 %) in the group without CSFD had paraplegia develop.In contrast,only two patients in the CSFD group(2.6%) had postoperative paraplegia(P =0.013).Stepwise logistic regression analysis identified CSFD had spinal cord protection,P =0.026;OR =0.171;95% CI:0.036-0.809).No patients occurred CSF catheter related complications.Conclusion This randomized clinical trial showed that preoperative CSFD placement could be an effective strategy in preventing SCI following extensive aortic aneurysm repair.Care should be taken to prevent complications related to overdrainage.
8.A review on viral myocarditis-related viruses and pathogenesis
Xiaotong SHAN ; Hongxiang LIN ; Yilin WANG ; Chengxi WEI ; Ying YU ; Ming ZHAO
Journal of Chinese Physician 2016;18(9):1425-1428
Viral myocarditis (VM) refers to human infections thermophilic myocardium virus that causes the circumscribed or diffuse myocardium-inflammatory lesion.Myocarditis can be caused by a variety of microbial infections,and VM is the most common one.In order to make the medical staff in clinical work have a more in-depth understanding of VM,this paper describes the common rviruses related,VM and its pathogenesis,process.At present,there is no effective drug and treatment method for VM.It is particularly important to further study the pathogenesis of VM on the role of the virus in,and inhibit its role in the further exploration of clinical therapeutic targets,to improve the quality of life of patients with VM and prolong the survival time is of great significance.Studying in-depth virus in the pathogenesis of VM and restraining its function are particularly important for the further exploration of clinical therapeutic targets.It is significant to improve the life quality and prolong the survival time for VM patients.
9.Symptomatic M1 stenosis of middle cerebral artery: the correlation between stenosis ratio and CT perfusion
Wei WANG ; Weijian JIANG ; Yongjun WANG ; Xiaotong XU ; Xinjiang ZHANG ; Zhensheng LIU ; Cheng LI
Chinese Journal of Neurology 2011;44(3):182-187
Objective To quantitatively analyze the correlation between stenosis ratio and cerebral perfusion in patients with solely symptomatic M1 stenosis of middle cerebral artery.Methods All the patients with solely symptomatic M1 stenosis of middle cerebral artery were selected to this study from consecutive 203 patients with elective stenting of symptomatic intracranial artery stenosis.Brain CT, CT perfusion (CTP) and DSA examinations were performed in all cases.The CTP parameters of mean transit time (MTT), cerebral blood flow (CBF) and cerebral blood volume (CBV) were measured in regions of interest (ROIs) including bilateral frontal lobe, anterior watershed, opercula of the insula (including parsopercluaris and part of insula), temporal lobe, posterior watershed and occipital lobe.Compared with the unaffected side as control, the change of CTP and their relative CTP parameters in these ROIs at affected side were analyzed.Based on DSA data, the ratio of M1 stenosis was measured manually and blindly, the source of collateral branch of compensative artery was estimated and the blood flow was graded.Correlation between the ratio of M1 stenosis and the CTP parameters including the absolute and the relative values was investigated.Results Twenty patients were selected into this study; their average M1 stenosis ration of the affected side was 70.5% ± 10.6% (53% to 91%).Compared with the unaffected side, MTT and CBF were no significant change but CBV increased in the affected frontal lobe; MTT prolonged, CBF was normal and CBV increased in the affected anterior watershed and opercula of the insula; MTT prolonged, CBF and CBV had no significant difference in the affected temporal lobe; MTT prolonged, CBF decreased and CBV had no significant difference in the affected posterior watershed; MTT, CBF and CBV were normal in occipital lobe.Tissue perfusion gradually decreased from the front to the backward in all the M1 stenosis affected cerebral regions and the posterior watershed area was the only region at hemodynamic failure stage.Leptomeningeal vessels of the anterior cerebral artery were the major sources of compensative arteries shown in the DSA in all cases.The ratio of M1 stenosis was positively correlated (r =0.66, P =0.002) with the rCBV in posterior watershed and there is no significant correlation between the ratio and any other CTP parameters in any regions.Conclusions Associated with distribution of collateral compensative artery,tissue perfusion showed obvious spatial distribution at different level in different cerebral region.M1 stenosis ratio is positively correlated with rCBV in hemodynamic failure regions, and there is no correlation with tissue perfusion in hemodynamic compromise regions.
10.Pathogenic Genes and Protein Function Changes in a Congenital Hereditary Cataract Pedigree
Journal of China Medical University 2017;46(8):673-676
Objective We screened for mutations in an autosomal dominant congenital cataract pedigree by gene sequence analysis to provide a basis for genetic diagnosis of congenital cataract.Methods A Chinese family with congenital nuclear cataract was recruited for mutational screening of candidate genes by direct sequencing.We analyzed the differences between the CRYGD gene mutant and wild-type in terms of protein conformation and structural domains using bioinformatics methods.Results We detected a novel heterozygous variant c.451_452insGACT in exon 3 of CR YGD.Bioinformatics analysis showed that the mutated CRYGD protein structural domain became shorter,the conformation became simpler,and protein inner repeatability was altered,affecting protein function.Conclusion We found that the Tyr1 51X gene mutation of CRYGD can lead to congenital hereditary cataract.To date,this is the only detected frameshift mutation caused by an insertion in CRYGD gene mutations.