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.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.
4.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.
5.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.
6.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.
7.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.
8.Neuroprotective effects of nGBE against glutamate excitotoxicity
Jing SUN ; Changkai SUN ; Ming FAN ; Aishi DING ; Lin YIN ; Wei WU ; Xiaotong WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2000;0(01):-
AIM:To investigate protective effects of novel extract of Ginkgo biloba(nGBE) in different administration modes on glutamate-induced neuronal damage.METHODS: The values of Essential nGBE were obtained by supercritical CO_2 fluid extraction.Based on glutamate excitotoxicity of primary cultures from neonatal Wistar rats hippocampal,by use of Trypan blue dye staining,testing the lactate dehydrogenase leakage from cultured neurons and terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL) method,we examined glutamate-induced necrosis and apoptosis.The protective effects of nGBE in different administration modes(pre-treatment and post-treatment) were adopted and compared with the NMDA receptor uncompetitive antagonist MK-801 in acute-treatment.RESULTS:Treatment with nGBE in two administration modes all could increase ratio of surviving neuron,decrease LDH efflux and reduce ratio of neuron apoptosis in different degree,and the benefit of pre-treatment was superior to post-treatment,but inferior to MK-801.CONCLUSION:The extracts of Ginkgo biloba used nowadays in cerebrovascular disease as post-treatment have no prominent effect as far as their mechanism of antiexcitotoxicity.However they may have more value if they were used for precautionary intervention in high-risk population.
9.Midterm outcomes following acute kidney failure after surgery for acute type A aortic dissection
Wei SHANG ; Min MA ; Yipeng GE ; Nan LIU ; Xiaotong HOU ; Lizhong SUN
Chinese Journal of Thoracic and Cardiovascular Surgery 2017;33(5):300-303
Objective This study aims to analyze midterm survival and to assess the midterm mortality following acute kidney failure (AKF) of patients undergoing surgical treatment of acute type A aortic dissection.Methods Clinical data of the patients who underwent Sun's procedure from February 2009 to March 2015 were collected.Patients with preoperative dialysis were excluded.Data including preoperative cardiovascular diseases,serum creatinine leve1 and CPB time were gathered.The patients were divided into the group of AKF and the group of non-AKF accounting to require dialysis.The group of AKF was follow-up by phone.Midterm mortality was studied with Cox analysis and midterm survival was estimated by Kaplan-Meier analysis.Results 524 patients underwent aortic surgeries which AKF was occurred in 51 (51/524,9.7%) patients.Hospital mortality was 23.5% (12/51) in AKF group which seven death were strokes,three death were lower-extremity ischemia and two death were low cardio output.There were 2 patients dead with multi organ failure and paraplegia in first year.One reoperation patient because of anastomotic fistula was dead in fifth year.Only diabetes was independently associated with midterm mortality.Midterm survival for patients with AKF was 56% during a median follow-up of 30.5 months.Survival was equal between the subgroups of Cr > 200 mol/L and Cr < 200 mol/L(P =0.741).Conclusion AKF after acute aortic dissection was a severe complication and the incidence was 9.7%.In patients with AKF,diabetes was associated with increased mortality across follow-up.Five years survival was 56% not effected by preoperative Cr.
10.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.