OBJECTIVE: To introduce the application of reduction-sensitive polymeric micelles in the field of tumor targeting drug delivery. METHODS: In the past decades, tumor targeted drug delivery systems have become important research area because they promise to resolve several key therapeutical issues including low treatment efficacy and significant side effects. On the basis of published literatures, the recent developments in reduction-sensitive polymeric micelles used for tumor targeting drug delivery were reviewed, with an emphasis on their structure characteristics as well as their biomedical applications from the cellular level and animal level, respectively. RESULTS AND CONCLUSION: As a novel intelligent drug delivery system, reduction-sensitive polymeric micelles can effectively control drug release with low side effects and high therapeutic effects both in vitro and in vivo. It has great potential in tumor targeting drug delivery.

Objective To explore the pathogenesis of femoral head ischemic necrosis(FHIN),and to observe the clinical therapeutic effects of extracorporeal shock waves therapy(ESWT) for FHIN in soldiers.Methods With exclusion of the femoral head necrosis sAbsequent to femoral neck fracture,108 cases of FHIN in ARCO stage Ⅰ-Ⅲ period,induding 86 males and 22 females,with aged ranged from 17 to 25 years,were involved in the present study,and the treatment modality was chosen by patients voluntarily.In 50 patients,ESWT combined with drilling decompression procedure(ESWT group) was chosen,and 9-12kV(0.16-0.22mJ/mm2) of extracorporeal shock wave was applied on the second day after drilling decompression.X-ray and MRI of bilateral hip joints were taken and Harris hip score(HHS) was estimated at 6 and 12 months after treatment.58 patients chose the treatment of simple drilling decompression served as controls.The results of the two groups were analyzed by Student's paired t test.Results No aggravation of FHIN occurred in the two groups.The average ratio of necrosis zone in ESWT group was diminished by 22.9%,32.8% and 34.3%,respectively,in the stages of ARCO Ⅰ,Ⅱ and Ⅲ,and the improvement was better in ARCO Ⅱ and Ⅲ stages than that in control group(P

Objective To explore the morphological changes of human mesenchymal stem cells(hMSCs) after exposure to extracorporeal shock wave(ESW).Methods An optimal experimental energy dose of ESW was applied to hMSCs of passage one.The morphological changes were examined by using inverted phase contrast microscope(IPCM),transmission electron microscope and cytochemical staining.Results ESW of 5kV and 100 times could raise the viability and proliferation of the cells.In the hMSCs of passage 3-5,the multiplicative division was speeded up,and the cells in the nuclear fission phase were increased.In the hMSCs of passage 7-9,the volume of the cells increased,and the endoplasmic reticulum was expanded.The Golgi's apparatus was developed and the matrix of the cells was bunchy.In the hMSCs of passage 11,the multiplicative division was also detected.Conclusion The proliferation and differentiation of the hMSCs can be improved by the treatment of ESW.

Indoleamine 2,3-dioxygenase (IDO) is a kind of immune regulation enzyme.IDO is the only rate-limiting enzyme that can catalyze the oxidative clearage of indole ring in tryptophan and its catabolism along the kynurenine pathway.IDO1 is one of the important mechanisms in maternal immune tolerance,which participates in the regulation of maternal-fetal immune relationship.The newly discovered IDO2 also plays an important role in this relationship.The abnormal expression of IDO2 is associated with the male infertility.

Objective To investigate the efficacy of anatomic plate internal fixation in treatment of complex proximal humeral fractures combined with humeral shaft fractures.Methods This retrospective case series study included 58 patients with complex proximal humeral fractures combined with humeral shaft fractures admitted from July 1998 to July 2015.There were 31 males and 27 females,with a mean age of 63 years (range,18-86 years).According to the Neer classification of proximal humeral fractures,three-part fractures were noted in 42 patients and four-part fractures in 16 patients.Four patients were combined with compressed or splitting fractures of the head of humerus and 38 patients with dislocation of the shoulder.According to the site classification of femoral shaft fractures,proximal 1/3 shaft fractures were noted in 36 patients,middle and distal 1/3 shaft fractures in 19,and multisegmental shaft fractures in three.All patients underwent anatomic reduction and anatomic plate internal fixation.Bone healing,Neer score of function outcome and complications were evaluated after operation.Results Mean duration of follow-up was 8.6 years (range,1-18 years).Bone union was observed in all patients after 10 to 24 weeks (mean,14.5 weeks).According to the Neer score,the outcomes were excellent in 23 patients,good in 25,fair in eight and poor in two,with the excellent rate of 83 ％.Complications such as infection,nerve injury and vascular injury were not observed after operation.Six patients suffered from limitations of shoulder anterior flexion and rise,one patient had humeral head necrosis and treated by shock wave treatment,and one patient had poor incision healing with hemorrhagic effusion and cured after dressing.Conclusion Anatomic plate internal fixation can contribute to fast functional recovery and few complications in treatment of complex proximal humeral fractures combined with humeral shaft fractures.

Humans ; Oral Surgical Procedures ; instrumentation ; methods ; Robotics ; instrumentation ; methods ; Surgery, Computer-Assisted ; instrumentation

OBJECTIVETo observe the effect and safety of plastering Chinese Compound Shenhuang Ointment (CSO) at Shenque (RN8) in promoting the rehabilitation of postoperative gastrointestinal dysfunction patients of qi stagnation blood stasis syndrome (QSBSS).

METHODSA prospective, multi-centered, randomized, double-blinded, controlled trial was conducted in 220 postoperative gastrointestinal dysfunction patients of QSBSS. They were randomly assigned to two groups, the CSO group (110 cases) and the placebo group (110 cases). CSO was plastered at Shenque (RN8) for 5 days after operation. The time of exhaustion, defecation, the recovery of intestinal peristalsis, integrals of TCM syndrome, and serum levels of motilin (MOT)and somatostatin (SS) were observed.

RESULTSCompared with the placebo group, the condition of exhaustion and defecation, the recovery of intestinal peristalsis on the 3rd day after operation was all improved (P < 0.05). The integrals of TCM syndrome at day 2, 3, and 4 were more significantly lowered in the CSO group than in the placebo group (P < 0.01, P < 0.05). The total effective rate of TCM syndrome was 95.3% in the CSO group, better than that in the placebo group (91.8%, P < 0.05). Compared with the placebo group, the serum MOT level increased and the serum SS level decreased at day 5 after operation in the CSO group (P < 0.05).

CONCLUSIONSThe plastering of CSO at Shenque (RN8) could advance the time of exhaustion and defecation, and improve patients' clinical symptoms. And patients could tolerate well.

Aged ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Gastrointestinal Diseases ; drug therapy ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Ointments ; Postoperative Period ; Prospective Studies

Aim The effect of tetrandrine on TGF-?1 mRNA expression in glomerulosclerosis rat was observed. Methods The rats were randomly divided into four groups, such as the normal control group (sham operative rat), glomerulosclerosis model group,tetrandrine group and amlodipine group. The expression of TGF-?1 mRNA was analyzed by Northern blot hybridization. Results The expressions of TGF-?1 mRNA in two treating groups were much lower than untreated model group. There were no difference between these two treating groups. Conclusion Tetrandrine can decrease the expression of TGF-?1 mRNA in glomerulosclerosis rat induced by unilateral renctomy plus adriamycin.

Background Arresting the overexpression of vascular endothelial growth factor (VEGF) will be a new approach to the inhibition of neovascularization.RNA interference (RNAi) can inhibit the expression of specific gene,and its application in eye has little interference to other gene expression.Objective This study was to investigate the effect of small interference RNA (siRNA) targeting VEGF on the expression of VEGF and retinal neovascularization in oxygen-induced retinopathy (OIR) model.Methods psi-HITM/enhanced green fluorescent protein (EGFP)/VEGF siRNA was designed and prepared in vitro.Mouse endothelioma (EOMA) were cultured in DMEM without antibiotic and divided into 5 groups.The cells were incubated in DMEM only in the blank control group;while 1 μl of LipofectamineTM 2000 + psi-HITM/EGFP,1 μl LipofectamineTM 2000 + 40,50 or 60 nmol/L of psi-HITM/EGFP/VEGF siRNA was added into DMEM in the negative control group and siRNA groups,respectively.The expression of VEGF mRNA and protein was detected by real time PCR (RT-PCR) and Western blot.The optimal effective concentration of VEGF siRNA was assessed.OIR models were established in 48 7-day-old C57BL/6J mice by raising them at an oxygen concentration of (75±2) ％ for 5 days and then to normal air.The mice were randomized into the model group,null vector group and VEGF siRNA group.1 μl of a mixture of psi-HITM/EGFP or VEGF siRNA (60 nmol/L) and LipofectamineTM 2000 was intravitreally injected,respectively,in the null vector group and VEGF siRNA group.The normal mice were used as the normal control group.Expression of VEGF mRNA and protein in the mouse retinas was detected by RT-PCR and Western blot,respectively,and FITC-dextran stretched retinal preparation was examined to evaluate the neovascularization,and retinal sections were examined to quantify the number of vascular endothelial cell nuclei extending beyond the internal limiting membrane (ILM).Results The in vitro transfection test showed that the expression of VEGF mRNA and protein in the EOMA cells was significantly different among the blank control group,negative control group and 40,50,60 nmol/L VEGF siRNA groups (F =148.890,P ＜ 0.001; F =306.960,P ＜ 0.001),and the expression of VEGF mRNA was lower in different concentrations of VEGF siRNA groups than that in the blank control group (t=73.950,119.890,156.480,all at P＜0.001).Also,the expression of VEGF protein was less in different concentrations of VEGF siRNA groups than that in the blank control group (t =15.452,23.344,42.119,all at P＜0.001).The optimal inhibitory concentration of VEGF siRNA was 60 nmol/L.In vivo study determined that compared to the model group and null vector group,the non-perfusion zones and neovascular net in the retina were decreased,and the number of vascular endothelial cell nuclei extending beyond the ILM was less in the VEGF siRNA group.The relative expression level of VEGF mRNA in the retinas was 1.23±0.18,4.02±0.16,3.98±0.19 and 1.98±0.12 in the normal control group,model group,null vector group and VEGF siRNA group,respectively,with a significant difference among them (F=369.780,P＜0.001),and the relative expression levels of VEGF mRNA in the model group and null vector group were higher than that in the normal control group (t=37.880,37.336,both P＜0.001),and the expression of VEGF mRNA in the VEGF siRNA group declined by 50.8％ (t=10.183,P＜0.001).The difference in the expression levels of VEGF protein also was assayed among the various groups (F=408.980,P＜0.001),and VEGF level in the retina was lowered by 68.0％ in the VEGF siRNA group compared to the model group (t =11.473,P＜0.001).However,VEGF level in the VEGF siRNA group remained at a high level in comparison with the normal control group (t =2.422,P＜0.001).Conclusions Intravitreal injection of VEGF siRNA can attenuate retinal neovascularization by effectively downregulate the expression VEGF mRNA and protein in the retina.

ObjectiveTo investigate the relationship between the degenerative mechanisms of lumbar intervertebral disc (LID) and apoptosis.MethodsThe total RNAs were isolated from human LID tissues. Both the mRNAs from the degeneration and normal LID were reversely transcribed to the cDNAs. The cDNAs were labeled with the incorporations of fluorescent dUTP, for preparing the hybridization probes. The mixed probes were then hybridized to the cDNA microarray. After high-stringent washing, the cDNA microarray was scanned for the fluorescent signals and analyzed by computer image analysis. The apoptotic status and the expression of Bcl-2 and Bax in 12 cases of degenerative LID and 10 cases of normal LID were detected with TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunohistochemistry methods.ResultsAmong the 4096 targets, there were 10 genes related to apoptosis. The expression related to Bax protein gene was up-regulated and it was down-regulated for Bcl-2 protein. In group of normal LID, the average apoptotic index (AI) was (24.897±3.620); percentage of Bcl-2 positive cells was (31.440±4.150)%; percentage of Bax positive cells was (29.372±2.588)%, average optical density (OD) values of positive particles were (0.183± 0.010 ), ( 0.203 ±0.012) and (0.169±0.005) respectively. In group of degenerative LID, the average AI was (49.232±3.440); percentage of Bcl-2 positive cells was (18.239±2.470)%; percentage of Bax positive cells was (52.349±3.764)%; average OD values of positive particles were (0.152±0.003), (0.310±0.008) and (0.262±0.014) respectively. There were significantly differences in AI and expressions of Bcl-2 and Bax proteins between normal LID and degenerative LID (P<0.05).ConclusionCell apoptosis plays an important role in the process of LID degeneration. Both Bcl-2 and Bax take part in the occurrence and progression of LID.