1.Novel strategies for promoting tumor penetration of anticancer nanomedicines
Jing HUANG ; Jun-na ZOU ; Huan-huan REN ; Shan WANG
Acta Pharmaceutica Sinica 2022;57(6):1758-1770
There is a broad and urgent need for the clinical application of anticancer nanomedicine in tumor therapy, but the complex biological barrier in solid tumors has always been the main obstacle to infiltrating nanomedicine into the tumor. The traditional design of nanomedicine based on enhanced permeability and retention (EPR) effect still has some limitations in tumor permeability, it is urgent to find other design theories. Therefore, this review summarizes two novel strategies, active transcytosis and immune cell-mediated tumor penetration, for promoting tumor penetration of anticancer nanomedicine.
2.Clinical Features of Acute Leukemia with Positive Mixed Lineage Leukemia Fusion Gene in Children
Journal of Applied Clinical Pediatrics 2006;0(20):-
Objective To analyze the clinical features of acute leukemia(AL) with positive mixed lineage leukemia(MLL)fusion gene in children,and explore their treatment protocols,prognosis factors,and so on.Methods Clinical features,treatment protocols,and prognosis factors were studied retrospectively among 51 AL patients with MLL fusion gene.MLL fusion gene was detected by morphology immunology,cytogenetics,molecul arbiology and reverse transcrption polymerase chain reaction(RT-PCR).Results Fifty-one AL patients with MLL fusion gene positive,included 37 cases of acute lymphoblastic leukemia(ALL) and 14 cases of acute myelocytic leukemia(AML).Forty-two patients exhibited abnormal clonal chromosome 11.MLL fusion gene rearrangements and MLL fusion gene partial tandem duplication were found among 36 cases and 15 cases,respectively.Thirty-two cases who received regular chemotherapy were followed up.Twenty-four cases including 19 cases of ALL and 5 cases of AML had achieved complete remission(CR).Six cases including 5 cases of ALL and 1 cases of AML had achieved more than 2 years CR.Sixteen cases were alive update including 12 cases of ALL and 4 cases of AML.Ten cases of positive MLL fusion gene were turning negative.Up to now,6 cases relapsed and 6 cases were dead.Conclusions The incidence of AL children with positive MLL fusion gene is low.It has some features,such as,high replapse rate and poor prognosis.A few patients sensitive to chemotherapies can achieve CR.They live with constant negative MLL fusion gene.
3.Application of Autogeneic Cartilage in Hearing Reconstruction Surgery
Huan JIA ; Zhaoyan WANG ; Qi HUANG ; Jun YANG ; Hao WU
Journal of Audiology and Speech Pathology 2013;(5):443-446
Objective To study the applications and outcomes of using autogeneic cartilage in hearing recon-struction surgery in patients with chronic otitis media or cholesteatoma .Methods A total of 165 patients (173 ears) in whom autogeneic cartilage was used were analyzed retrospectively .Forty -three patients (48 ears) had simple tympanic membrane perforations ,61 patients (61 ears) had cholesteatomas including 12 retraction pockets ,23 pa-tients (23 ears) had tympanoscleroses and 38 patients (41 ears) had otitis media with granulations .The cartilage grafts were used for tympanic perforation reparing in 133 patients (139 ears) ,for ossiculoplasty in 102 patients (104 ears) ,for attic reconstruction in 31 patients (31 ears) and for canal wall reconstruction of external auditory canal in 3 patients (3 ears) .The auditory outcome (0 .5 ,1 ,2 ,and 4 kHz pure tone average hearing threshold ,the average air-bone gap) and local architecture status were followed up for 1 year after surgery .Results In 133 patients (139 ears) with tympanic perforation ,the rate of successful repair of a tympanic membrame perforation in one -stage was 97 .84% with perforation repair in 136 ears and postoperative perforation in 3 ears .In 102 patients (104 ears) of os-siculoplasty ,there was no ossicular prostheses prolapse .In 31 patients (31 ears) of attic reconstruction ,no local graft shift or collapse was found .In 3 patients (3 ears) of external auditory canal repair ,no canal wall collapse occurred . In myringoplasty group (43 patients ,48 ears) ,preoperative and postoperative air -bone gap (ABG) was 23 .8 ± 3 .1 dB and 11 .6 ± 8 .7 dB ,respectively .In cholesteatoma group (61 patients ,61 ears ) ,preoperative and postoperative ABG were 39 .2 ± 24 .7 dB and 19 .0 ± 12 .1 dB ,respectively .In tympanosclerosis group (23 patients ,23 ears) ,pre-operative and postoperative ABG were 31 .2 ± 12 .4 dB and 19 .8 ± 11 .2 dB ,respectively .In otitis media with granu-lation group (38 patients ,41 ears) ,preoperative and postoperative ABG were 41 .6 ± 9 .9 dB and 15 .3 ± 13 .4 dB ,re-spectively .Conclusion Autogeneic cartilage is very valuable in hearing reconstruction surgery ,especially in compli-cated tympanic perforation ,combination with ossiculoplasty prostheses ,or reconstruction of mastoid cavity or exter-nal call wall defect .
4.An observation of clinical effect of hydrocortisone sodium succinate injection on patients with septic shock
Huan LIANG ; Jun WANG ; Changqing MIAO ; Jiayan NAN ; Bo PENG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2014;26(2):88-90
Objective To investigate the clinical efficacy of hydrocortisone sodium succinate for treatment of septic shock patients and their prognoses. Methods A prospective case control study was conducted. 49 patients with septic shock in the Department of Emergency of the First Affiliated Hospital of Xi'an Jiaotong University were enrolled from January 2010 to January 2012,and the patients were sequentially divided into two groups,the treatment group(24 cases)and the control group(25 cases),by the difference in odd or even number. All patients in the two groups accepted the conventional treatment. The treatment group additionally received hydrocortisone sodium succinate injection 200 mg,once a day for 5 days. The levels of serum procalcitonin(PCT),C-reactive protein(CRP)were measured in all the patients before treatment and 24 hours,72 hours and 7 days after treatment. The mortalities were compared in 14 days between the two groups. Results The levels of PCT,CRP before and 24 hours after treatment were not statistically significant different from those of pre-treatment in two groups(all P>0.05). PCT and CRP were decreased at 72 hours and 7 days after treatment in the two groups,and on the 7th day the decline was more significant, and compared with the control group,the levels of PCT and CRP in treatment group were reduced more markedly at 72 hours and on the 7th day〔PCT(μg/L):72 hours 9.73±2.10 vs. 12.36±2.56,7 days 5.33±2.05 vs. 8.76±1.78;CRP(μg/L):72 hours 69.12±13.61 vs. 109.68±16.16,7 days 20.16±9.64 vs. 42.32±13.16,all P<0.05〕. But the mortality in 14 days was not statistically significant different between control group and treatment group(52.0%vs. 45.8%,P>0.05). Conclusion The treatment with hydrocortisone sodium succinate can reduce the inflammation of patients with septic shock,thus it has clinical value in the improvement of the disease situation.
5.Study on Changes of LFA-1 Level in Peripheral Neutrophils in Patients with Severe Preeclampsia
Jun WEI ; Wei WANG ; Huan TANG ; Xiaozhu WU ; Caixia LIU
Journal of China Medical University 2015;(3):263-266
Objective To check the neutrophil count and the expression of cell surface adhesion molecule,lymphocyte function associated antigen?1(LFA?1)in peripheral neutrophils in severe preeclamptic patients and normal pregnant women in order to investigate the correlation of neutrophil activation with preeclampsia. Methods Totally 28 pregnant women in the department of gynecology and obstetrics in Shengjing Hospital from No?vember 2013 to January 2014 were included in the study,and divided into the severe preeclampsia group(n=14),and the control group(normal pregnant women,n=14). There was no statistically significant difference in age and gestational weeks between the two groups. The expression of LFA?1 in peripheral neutrophils was detected by flow cytometry in the two groups. Mean blood pressure(MBP)was measured in the severe preeclamptic group,and the correlation of MBP with expression of LFA?1 was analyzed. Results The neutrophil count was 8.40±2.23 ×109/L in the severe pre?eclamptic group,significantly higher than(6.71±1.58)×109/L in the control group,(P<0.05). The positive rate of LFA?1 in peripheral neutrophils was 63.25±38.025%in the severe preeclamptic patients,significantly higher than 8.32±38.65%in the control group(P<0.05). The expression lev?el of LFA?1 in peripheral neutrophils was significantly correlated with mean blood pressure in severe preeclamptic patients(r=0.64,P=0.013). Conclusion The neutrophil count and the expression of LFA?1 in peripheral neutrophils were significantly increased in severe preeclamptic pa?tients compared to normal pregnant women,and significantly correlated with severity of preeclampsia,suggesting that neutrophil activation participat?ed in the pathogenesis of preeclampsia.
6.Determination of Serum Concentration of Triptolide in Patients with Rheumatoid Arthritis and Its Pharmacokinetics Study
Ying LI ; Yongzhong WANG ; Huan LUO ; Chuanbing HUANG ; Jun ZHU
Chinese Journal of Information on Traditional Chinese Medicine 2014;(1):85-87
Objective To establish an UPLC method for determination of Triptolide in serum and explore its pharmacokinetics in patients with rheumatoid arthritis after oral administration of tripterygium glycosides tablet. Methods Three patients with rheumatoid arthritis were enrolled. Using Estazolam as internal standard, serum was extracted with acetic ether, and determination was performed on column of Waters Acquity C18 (2.1 mm×100 mm, 1.7 μm) with mobile phase consisted of acetonitrile-0.1% glacial acetic acid (30∶70) at the flow rate of 0.2 mL/min. The column temperature was 30 ℃, and the detection wavelength was set at 220 nm. The serum concentration of Triptolide was processed by DAS 2.1.1 computer program. Results Triptolide was well-separated from internal standard, and the retention time were about 4.9 min and 8.9 min, respectively. Linear range of Triptolide was 13.13-840.00 ng/mL. RSD of intra-day and inter-day were lower than 15%and the recoveries were 88.25%-99.33%. Pharmacokinetic parameters were as follows:Cmax was (159.97±42.43) ng/mL, Tmax was (1.33±0.58) h, T1/2βwas (7.51±2.26) h, and AUC0-12 h was (1131.12±89.20) mg?h/L, respectively. Conclusion Pharmacokinetics of Triptolide conformed to two compartment model. Triptolide can be quickly absorbed, and exists differences among individuals.
7.The diagnostic value of ultrasound elastography in breast tumor and analyze the significance of joint DWI
Jun WANG ; Huan LU ; Jun YE ; Shaoqiang LIU ; Hongyu XU ; Zihui SU ; Ting WU
Chongqing Medicine 2015;(9):1224-1225,1228
Objective To evaluate the value of ultrasound elastography in the diagnosis of breast tumor ,and compared with imaging analysis .Methods To collect the image data of 160 patients ,confirmed by pathology ,a total of 182 ,preoperative ultra-sound elasticity imaging and DWI ,ultra sonic elastography diagnosis by five points method ,DWI on the basis of the measured ADC value in the diagnosis of lesions ,respectively compared with pathology .Results Ultrasound elastography diagnosis of 89 malignant tumors ,of which the correct diagnosis of 78 malignant tumors ,7 misdiagnosis ,11 benign misdiagnosed as malignant diagnosis;93 benign tumors ,86 of correct diagnosis ,11 misdiagnosis ,7 malignant misdiagnosed as benign ,sensitivity was 87 .6% ,specificity of 92 .5% ,the Accuracy was 93 .9% ;ultrasound elastography and DWI combined imaging diagnosis of 86 malignant tumors ,81 correct diagnosis of malignant tumors ,4 misdiagnosis ,5 from the benign misdiagnosed as malignant diagnosis ,96 benign tumors ,92 correct diagnosis ,5 misdiagnosis ,the sensitivity was 94 .1% ,specificity of 95 .8% ,the accuracy was 97 .2% .Conclusion Ultrasound elas-tography in breast benign and malignant tumor diagnosis with higher sensitivity and specificity ,accuracy ,joint DWI can significantly improve the sensitivity and specificity of breast benign and malignant tumor diagnosis ,accuracy .
8.Repairing segmental bone defect by gene enhanced tissue engineering bone with microsurgery methods
Jian-Jun LI ; Qun ZHAO ; Huan WANG ; Jun YANG ; Quan YUAN ; Shao-Qian CUI ; Lei LI ;
Chinese Journal of Microsurgery 2006;0(05):-
E were all found in the above three aspects (P
9.Establishment and application of screening methods for non-agonist PPARγ ligand.
Yi HUAN ; Jun PENG ; Yue WANG ; Chunming JIA ; Ke WANG ; Kehua WANG ; Zhiqiang FENG ; Zhufang SHEN
Acta Pharmaceutica Sinica 2014;49(12):1658-64
In-vitro assay methods were established to evaluate transactivation and binding activity of compounds on peroxisome proliferator-activated receptor y (PPARγ). Firstly, plasmids were constructed for transactivation assay of PPARγ response element (PPRE) triggered reporter gene expression, and for cell-based binding activity assay of the chimeric receptor, which was fused with PPARγ ligand binding domain (LBD) and yeast transcriptional activator Gal4. Secondly, by using PPARy competitive binding assay based on time resolved-fluorescence resonance energy transfer (TR-FRET), affinities of compounds and drugs to PPARγ were evaluated. In application of these above methods, the PPARγ activating potency and characteristics of different compounds were evaluated, and a novel benzeneselfonamide derivative, ZLJ01, was found to have comparable binding activity and affinity with the well-known PPARy agonist, but lack of PPRE mediated transactivation activity. In preliminary study on in-vitro hypoglycemic activity, ZLJ1 was found to promote insulin-stimulated glucose uptake by liver cells. Therefore, we believe that combining transactivation and binding activity as well as affinity evaluation, the system could be used to screen non-agonist PPARγ ligand as anovel PPARγ modulator
10.Association of genetic polymorphisms in the DNA repair gene XRCC1 and XPD with risk of prostate cancer
Jie LIU ; Bao SONG ; Hong WANG ; Jun TIAN ; Zhen CHEN ; Huan SHI ; Zhehai WANG
Chinese Journal of Urology 2009;30(12):834-837
Objective To explore the relationship between DNA repair gene XRCC1 and XPD polymorphisms and individual susceptibility to prostate cancer. Methods PCR-restriction fragment length polymorphism assay was used to analyze the XRCC1 (C26304T and G28152A) and XPD A35931C polymorphisms in 358 prostate cancer patients and 312 healthy controls. Unconditional logistic regression analysis was performed to calculate odd ratio (OR) and 95% confidence interval (CD for estimating the correlation between different genotypes and prostate cancer risks. Results Forty-seven(13.1%) cases present XRCC1 28152AA genotype in prostate cancer group, while 24 cases in the control group (7. 1%), individuals with this genotype had a significantly increased risk for prostate cancer (OR 1. 924, 95%CI=1.126 - 3. 288, P=0. 017). There was no significant difference between two groups at XRCC1 C26304T and XPD A35931C sites. Combined analysis of the three sites polymorphisms showed that individuals with XRCC1 28152 AA and XPD 35931AC+CC genotype had a higher risk of prostate cancer than those with three wild genotypes (OR = 3. 087,95%CI 1. 081 - 8.813;OR = 3. 376,95%CI 1.067-10.683;OR 3. 216,95%CI=1. 439-7.188,P = 0. 004). Analysis stratified by age of onset, PSA, Gleason score and T stage revealed that XRCC1 28152AA and XPD 35931 AC+CC high-risk genotype was especially associated with early age at onset of prostate cancer (P<0. 05). Conclusions The XRCC1 and XPD genotypes may be contributed to the risk of developing prostate cancer, particularly for younger patients.