Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents ; chemistry ; Drug Carriers ; chemistry ; Liposomes ; chemistry ; Polyethylene Glycols ; chemistry

Objective To investigate the clinical values of next-generation sequencing (NGS) technology in diagnosis of miscarried chorionic villi genetic disorders. Methods Patients who underwent miscarriage (n=87) were enrolled in this study. Among all patients, 32 cases were of recurrent miscarrage and 55 cases were of sporadic miscarriage. In all collected patients, 35 women were 35 years or older while other 52 women were less than 35 years old. Positive detection rate and the abnormal detection rate were compared between these two methods. Chromosomes abnormal rates were also compared among different types of miscarrage and different ages. All aborted villi tissue were analyzed by NGS of whole genome and G-band?ing karyotype. Results The successful detection rate of chorionic villi by NGS (100.00%) was higher than that of G-band?ing karyotype (74.71%), and the detection rate of abnormal chorionic villi by NGS (58.62%) was also higher than that of G-banding karyotype (50.77%). Three cases of chromosome structure anomaly were found in those 51 chromosome anomalies (5.88%). Other 48 cases of chromosome anomalies were aneuploidy anomalies (94.12%) include 39 cases of trisomy, 2 cases of double trisomy and 1 case of triple trisomy and 6 cases of monomer. On the other hand, 32 cases of chromosome aneuploi?dy anomalies were found in 33 chromosome anomalies by G-banding karyotype, which include 24 cases of trisomy, 2 cases of double trisomy, 1 case of triple trisomy, 5 cases of monomer and 1 case of chromosome structure anomaly. Most NGS re?sults (n=64) were in agreement with G-banding karyotype but with 1 case of discrepancy. Chromosomal abnormality rate de?tected by NGS in sporadic miscarrage group and recurrent spontaneous miscarrage group were 60.00%and 56.25%respective?ly. There was no significant difference (P>0.05). Chromosomal abnormality rate picked by NGS in women aged≥35 years old (71.43%) was higher than that in women<35 years old (50.00%) with statistically significant difference (P<0.05). Conclu?sion NGS technology showed highly accuracy in detecting chromosomal abnomality from villi tissue. Therefore, it could help to detect genetic disorders of miscarrage. It is useful to determine the reasons of miscarrage and guide the next pregnancy.

Objective:To investigate the efficacy of sequential therapy of CD19 and CD22 chimeric antigen receptor T cells (CAR-T) for relapsed/refractory mediastinal B lymphoblastic lymphoma (B-LBL).Methods:One patient with relapsed/refractory mediastinal B-LBL treated with sequential therapy of CD19 and CD22 CAR-T who was admitted to Tongji Hospital of Huazhong University of Science and Technology Tongji Medical College in March 2017 was reported. At 1, 3, 6, 12 and 18 months after CAR-T therapy, the indicators of primary disease remission were monitored and the relevant literature was reviewed.Results:The patient relapsed and progressed after third-line chemotherapy, and then received sequential therapy of CD19 and CD22 CAR-T. In the course of cellular immunotherapy, the patient presented grade 1 cytokine release syndrome. After active treatment, the patient got stable condition and was discharged. The patient came to the hospital for regular review, and the mediastinal mass of the patient was dynamically followed up. After CAR-T therapy, the mediastinal mass of the patient was significantly reduced, and the patient was in continuous remission for 18 months.Conclusions:Sequential therapy of CD19 and CD22 CAR-T provides a new therapeutic approach for relapsed/refractory B-LBL. For patients with poor curative effect of conventional chemotherapy, CAR-T therapy should be actively performed as soon as possible to improve the remission rate and the long-term prognosis of patients.

Objective To investigate the imaging features of the calvarial cavernous hemangioma and the surgical efficacy to improve diagnosis and treatment of the calvarial cavernous hemangioma.Methods The clinical information,imaging materials and surgical efficacy from ten cases of calvarial cavernous hemangioma confirmed by pathology and the related literature was reviewed.Results The lesion was located in frontal bone in eight cases,in parietal bone in one case and in occipital bone in one case.The lesions were round-shape hypodensity with clear margin in X-ray.The lesions were hyperdensity or slightly hyperdensity on CT scan,and were osteolytic lesions with a characteristic honeycomb or starburst pattern on bone window.The MRI features were complicated and variable.The lesions were heterogenous and unevenly enhanced signal intensity.Nine patients underwent radical resections and reconstructed immediately by titanium mesh.The patient with tumor in occipital bone underwent radical resection only.Macroscopically,the pathologic bone was a huge purple-red blush mass protruding from the skull surface.Histological examination revealed the diploe with large,thin-walled,dilated blood-filled spaces lined by flattened endothelial cells without evidence of malignancy.No recurrence was noted in any case during a follow-up period from 3 to 24 months.All the patients survived well without recurrence.Conclusions The imaging features of calvarial cavernous hemangioma have a high value in the diagnosis and may provide guidance for the treatment.The radical resection and immediate reconstruction treatment for calvarial cavernous hemangioma is satisfied.

Aim To investigate the role of GC in indu-cing apoptosis of amygdaloid neurons.Methods Cul-turing primary neurons of amygdala,the neurons were identified by immunefluorescence techniques with anti-body against microtubule associated protein-2 (MAP2 ) and antibody against GC receptor.Using flow cytome-try to detect the effects of different concentrations of dexamethasone on the amygdala neuron apoptosis. Then the experiment was divided into four groups:CON ,DEX ,DEX +MIF and MIF .The rate of apopto-sis of the four groups was detected by TUNEL tech-nique and the expressions of BAX mRNA of four groups by Real-time PCR technique.Results (1 )Compared with the control group, the percentage of apoptotic cells increased significantly with DEX(10 -8 mol·L-1~10 -6 mol · L-1 )treatment in a concentration-de-pendent manner.(2)the TUNEL test showed that the percentage of apoptotic cells of DEX group increased significantly,compared with control group.While it decreased significantly in DEX+MIF group,compared with DEX group.There was no difference between MIF group and control group.(3 )Compared with control group,the expressions of BAX mRNA of DEX group increased significantly.While the expressions of BAX mRNA of DEX +MIF group decreased significantly, compared with the DEX group.There was no difference between MIF group and control group.Conclusion GC can independently induce the apoptosis of primary cultured neurons in the amygdala by combining with GC receptor.

Objective To investigate the effect of endovascular treatment of intracranial ruptured vertebral artery dissecting aneurysms via bilateral vertebral artery approach. Methods The symptoms and imaging results of 5 patients with ruptured vertebral artery dissecting aneurysms were analyzed retrospectively. They were all treated with coil embolization via bilateral vertebral artery approach. The two ends of dissection aneurysms were packed densely,the middle segments were packed loosely,and the arteries were isolated from the blood circulation. Results Of the 5 patients after treated,the clinical symptoms were improved rapidly in 4 patients no abnormal limbs activity and mental disorders. After treatment,the modified Rankin scale (mRS)was 0 in four cases after six-month follow-up. One patient turned clear consciousness after 4 weeks, and their mRS was 3 at 6-month follow-up. Before treatment,DSA showed vertebral artery dilation and stenosis. The mean length of involvement in vertebral arteries was 9. 3 ± 1. 5 mm;after treatment,the dissecting aneurysms of 5 patients did not develop completely,no further bleeding occurred,and no new infarcts were observed. No recurrence of the aneurysms and parent artery recanalization were found at the follow-up after 6 months. Conclusion The occlusion of ruptured vertebral artery dissecting aneurysms via bilateral vertebral artery approach is technically feasible. It may be an effective treatment to prevent rebleeding.

Objective To investigate the expression of VIT-1 gene in melanocytes of patients with vitiligo, and to analyze the difference of its sequence. Methods The skin from the foreskins of healthy men by circumcision and from the non-lesional area on the buttocks of 5 patients were digested by dispase, then the epidermis and dermis were separated, and the melanocytes were isolated. Then we cultured the melanocytes from the controls in TICVA medium and those from the patients in TICVA medium supplemented with basic fibroblast growth factor (bFGF) and endothelin-1 ( ET-1). The expression of VIT-1 gene was measured by RT-PCR, the full-length cDNA of VIT-1 ORF was cloned and sequenced, and sequence difference was analyzed by CLUSTAL W ( 1.83 ) software. Results The expression levels of VIT-1 gene were significantly lower in melanocytes from the patients than in those from the controls. An 81 bp-intron was found in the VIT-1 ORF. VIT-1 was a fragment of FBXO11, located at its 3' end. Conclusion VIT-1 gene is not a new gene, but a fragment of FBXO11, and a member of F-box protein family.

200 citrinin mutants were screened with the inhibition zone method from the transformants library of Monascus ruber M-7 by Agrobacterium-mediate DNA transfer, which contains more than 5,000 transformants.Then 53 mutants, whose citrinin contents ranged from 0.04?g/g to 154.57?g/g in the red fermented rice (RFR), were achieved by high performance liquid chromatography (HPLC).Color values of RFR prepared by these mutants were also detected.The results showed that there was a positive correlation between the citrinin content and the color value among the mutants.These results provide materials and research bases for ferrther studying the relationship between the production of citrinin and pigment of Monascus ruber at molecular level.

OBJECTIVETo investigate the brain functional laterality in motor areas during motor execution systematically.

METHODSFunctional magnetic resonance imaging (fMRI) was employed combined with right hand sequential finger movement task to investigate brain activation pattern and laterality in 8 right-handed subjects. 3dDeconvolve program of AFNI was used to estimate the hemodynamic response function and to generate activation maps. Then the laterality index (LI) was calculated and tested statistically.

RESULTAll motor areas including the areas which were previously considered to be engage in movement preparation only were activated in movement execution. In the activation map, it appeared left lateralization in cerebra and right lateralization in cerebella. After further statistical test, it was found that in primary motor area (M1), supplementary motor area (SMA) and posterior parietal cortex (PPC), there were left lateralization. While in premotor cortex (PMC), cingulate gyrus and basal ganglia (BG), the lateralization tendency was not obvious. The activation in cerebella is characterized with right lateralization.

CONCLUSIONThough there are tiny differences among subjects, most of the motor areas appear lateralized activation. Past studies only observed laterality in several motor areas. It may be due to the difficulty of the task or the experimental design.

Adult ; Brain ; physiology ; Female ; Functional Laterality ; physiology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Motor Cortex ; physiology

OBJECTIVETo study the effect and mechanism of bevacizumab on proliferation and invasion of human lung cancer A549 cells.

METHODSA549 cells were treated with bevacizumab. Proliferation and invasion of the bevacizumab-treated A549 cells were detected using cell counting kit CCK-8 and Transwell assay, respectively. The expression of the mRNA and protein of MMP-2, MMP-9 and c-Met were detected by real-time PCR and Western blotting, respectively.

RESULTSProliferation activity was inhibited at the concentration of 10 µg/ml and promoted at the concentration of 100 µg/ml bevacizumab. Bevacizumab in the concentration of 50 µg/ml had a stronger inhibitory effect on the invasion of A549 cells (16 406.19 ± 5 674.23 penetrated cells) than that of control group (36 108.68 6 263.83, P<0.05). The real-time PCR showed that bevacizumab had a stronger inhibitory effect on the expression of MMP-2 and MMP-9 mRNA at the concentration of 50 µg/ml and on the expression c-Met mRNA at the concentration of 10 µg/ml bevacizumabin the A549 cells. However bevacizumab at the concentration of 100 µg/ml showed a promoting effect on the expression of MMP-2, MMP-9 and c-Met mRNA (1.82 ± 0.31, 1.60 ± 0.25, 2.63 ± 0.48), significantly higher than that of the control group (1.00 ± 0.19, 1.00 ± 0.23, 1.00 ± 0.22, P<0.05). The expression of MMP-2, MMP-9 and c-Met mRNA and protein was inhibited by 10 µg/ml bevacizumab in a time-dependent manner. The Western blot assay showed that bevacizumab had a bi-directional effect on the expression of MMP-2 and c-Met proteins in the A549 cells: a promoting effect at 100 µg/ml and inhibitory effect on the expression of MMP-2 at 50 µg/ml bevacizumab, and inhibitory effect on the expression of c-Met protein at 10 µg/ml bevacizumab.

CONCLUSIONSOur findings indicate that in a certain range of concentrations, bevacizumab has prominent inhibitory effect on the proliferation and invasion of A549 cells. However,over the concentration of 100 µg/ml, bevacizumab shows a weakening anti-invasion effect, even has a promoting effect on cell proliferation. This phenomenon may be related to the inhibiting effect on the expression of MMP-2 and c-Met proteins in a non-concentration-dependent manner by bevacizumab.

Angiogenesis Inhibitors ; pharmacology ; Bevacizumab ; pharmacology ; Blotting, Western ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; drug effects ; Enzyme Inhibitors ; pharmacology ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-met ; metabolism ; RNA, Messenger ; metabolism ; Real-Time Polymerase Chain Reaction