Multidrug resistance (MDR) remains the major obstacle to the success of clinical cancer chemotherapy. P-glycoprotein (P-gp), encoded by the MDR1, is an important part with complex mechanisms associated with the MDR. In order to overcome the MDR of tumors, we in the present experimental design incorporated small interfering RNA (siRNA) targeting MDR1 gene and anticancer drug paclitaxel (PTX) into the solid lipid nanoparticles (SLNs) to achieve the combinational therapeutic effects of genetherapy and chemotherapy. In this study, siRNA-PTX-SLNs were successfully prepared. The cytotoxicity of blank SLNs and siRNA-PTX-SLNs in MCF-7 cells and MCF-7/ADR cells were detected by MTT; and the uptake efficiency of PTX in MCF-7/ADR cells were detected via HPLC method; quantitative real-time PCR and flow cytometry were performed to investigate the silencing effect of siRNA-PTX- SLNs on MDR1 gene in MCF-7/ADR cells. The results showed that PTX loaded SLNs could significantly inhibit the growth of tumor cells, and more importantly, the MDR tumor cells treated with siRNA-PTX-SLNs showed the lowest viability. HPLC study showed that SLNs could enhance the cellular uptake for PTX. Meanwhile, siRNA delivered by SLNs significantly decreased the P-gp expression in MDR tumor cells, thus increased the cellular accumulation of rhodamine123 as a P-gp substrate. In conclusion, the MDR1 gene could be silenced by siRNA-PTX-SLNs, which could promote the growth inhibition efficiency of PTX on tumor cells, leading to synergetic effect on MDR tumor therapy.
ATP Binding Cassette Transporter, Sub-Family B ; genetics ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; pathology ; Drug Delivery Systems ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Lipids ; chemistry ; MCF-7 Cells ; drug effects ; Nanoparticles ; chemistry ; Paclitaxel ; pharmacology ; RNA, Small Interfering ; pharmacology ; Real-Time Polymerase Chain Reaction

OBJECTIVETo reveal the possible mechanism involved in patella-femoral degenerative arthritis (PFDA) in- duced by torsion-deformity of tibia via analyzing the relationship between torsion-deformity of the tibia in patients with PFDA and the disorder of patella-femoral joint under the static and dynamic conditions.

METHODSFrom October 2009 to October 2010, 50 patients (86 knees, 24 knees of male patients and 62 knees of female patients) with PFDA were classified as disease group and 16 people (23 knees, 7 knees of males and 16 knees of females) in the control group. The follow indexes were measured: the torsion-angle of tibia on CT scanning imagings, the patella-femoral congruence angle and lateral patella-femoral angle under static and dynamic conditions when the knee bent at 30 degrees of flexion. Based on the measurement results, the relationship between the torsion-deformity of tibias and the disorders of patella-femoral joints in patients with PFDA were analyzed. Finally,the patients were divided into three groups including large torsion-angle group, small torsion-angle group and normal group according to the size of torsion-angle, in order to analyze the relationship between torsion-deformity and disorders of patella-femoral joint, especially under the dynamic conditions.

RESULTSCompared with patients without PFDA, the ones with PFDA had bigger torsion-angle (30.30 ± 7.11)° of tibia, larger patella-femoral congruence angle (13.20 ± 3.94)° and smaller lateral patella-femoral angle (12.30 ± 3.04)°. The congruence angle and lateral patella-femoral angle under static and dynamic conditions had statistical differences respectively in both too-big torsion-angle group and too-small torsion-angle group. The congruence angle and lateral patella-femoral angle under static and dynamic conditions had no statistical differences in normal torsion-angle group.

CONCLUSIONTorsion-deformity of tibia is the main reason for disorder of patella-femoral joint in the patients with PFDA. Torsion-deformity of tibia is always accompanied by instability of patella-femoral joint,especially under the dynamic condition, thus causing PFDA. It can not only provide arrangement information and degenerative condition of patella-femoral joint,but also provide guidance through the analysis on the relationship for better clinical prevention and early treatment of degenerative bone and joint disease.

Adult ; Female ; Femur ; diagnostic imaging ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; diagnostic imaging ; etiology ; Patella ; diagnostic imaging ; Radiography ; Tibia ; diagnostic imaging ; Torsion Abnormality ; complications ; diagnostic imaging

Background and purpose:Gene fusions have been identiifed as recurrent oncogenic events in lung adenocarcinoma. Our purpose are to study the histologic features of anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1) andRETproto-oncogene fusion-positive lung adenocarcinomas and to evaluate the correlation between psammoma bodies and fusion-positive lung adenocarcinomas.Methods:In this study, we performed a comprehensive histologic analysis of 44 fusion-positive (including 15RET, 20ALK and 9ROS1)
lung adenocarcinomas and 111 fusion-negative [including 20 epidermal growth factor receptor (EGFR), 20 Kirsten rat sarcoma viral oncogene (K-ras), 71 pan-negative] lung adenocarcinomas.Results:ALK,RET andROS1 fusion-positive lung adenocarcinomas were more prevalent in solid or acinar predominant adenocarcinoma. Multivariate analysis showed that tumors harboring a fusion gene had significantly higher prevalence of the presence of signet ring cells (P=0.000), micropapillary component (P=0.044), mucinous cribriform pattern (P=0.000) and extracellular mucin (P=0.010). The incidence of psammoma bodies was higher in the lung adenocarcinomas with a gene fusion than in tumors without gene fusions (P=0.000). Psammoma bodies were more likely to be found in tumors with any micropapillary component and/or mucinous cribriform pattern than in tumors lacking a micropapillary component and/or mucinous cribriform pattern (P=0.000).Conclusion:Our data showed that the presence of psammoma bodies, micropapillary component, mucinous cribriform pattern, extracellular mucin or signet ring cells may be either sensitive or speciifc to predict tumors harboring a fusion gene. These distinct morphologic features may be helpful in selecting cases for further accurate molecular testing.

Background Cataract phacoemulsification combined with intraocular lens (IOL) implantation is a primary treatment for cataract.However,tear film stability and ocular surface structure are affected after surgery,especially some cataract patients with diabetes.Researches determined that tear film dysfunction is an important causative factor of dry eye.Objective This study was to investigate the change of tear film after phacoemulsification in cataract patient with diabetes.Methods A non-randomized cases-controlled study was designed.Thirty-six cataract patients with diabetes (54 eyes)and matched 32 patients (40 eyes)with age-related cataract were included in this study in Tianjin First Center Hospital from October,2010 to May,2011.Phacoemulsification and IOL implantation was performed on the all patients with the same topical eyedrops in both groups.Dry eye-related symptom was surveyed and scored by questionnaire,and tear film break-up time (BUT),Schirmer Ⅰ test(S Ⅰ t)and corneal fluorescein(FL) were examined 3 days before operation and 1 day,1 week,1month,3 months after operation.Written informed consent was obtained from each patient before entering this trial.Results The percentage with preoperative symptoms of dry eye was 36.2％ and postoperative dry eye symptoms accounted for 75.8％.Significant differences were seen in dry eye symptom score,FL score,BUT value and S Ⅰ t value between the diabetic cataract group and only cataract group as well as among 4 time points(dry eye symptom score:Fgroup =139.347,P =0.000 ; Ftime =342.741,P =0.000 ; FL score: Fgroup =14.073,P =0.000 ; Ftime =332.697,P =0.000 ; BUT value: Fgroup =28.198,P =0.000 ; Ftime =868.364,P =0.000 ; S Ⅰ t value: Fgroup =2.848,P =0.095 ; Ftime =564.017,P=0.000).FL scores of 2 groups were significantly higher in postoperation than those in preoperation (P＜0.05),and those of diabetic cataract group were significantly higher than only cataract group(P＜0.05),but no significant difference was found between postoperation 3 months and preoperation (P＞0.05).BUT was shorter in postoperation than that in preoperation in the diabetic cataract group(P＜0.05).S Ⅰ t values in postoperative 1 day and 1 week were significantly lower than in preoperation in both groups(P＜0.05).However,S Ⅰ t values returned to normal from 1 month through 3 months in both groups(P＞0.05).Conclusions Tear film dysfunction occurs after operationin cataract patient with type 2 diabetes.It is thought that cataract patient with diabetes is susceptible population of dry eye.Dry eye appears more early and severer in diabetes patients after phacoemulsification combined with IOL implantation.

Using MRS medium, as imitating gastroenteric environments, such as low pH (1.5-4.5) and high bile salt (0.1%~0.4%), the antagonistic properties of Lactobacillus acidophilus were studied. At the same time, the antimicrobial activities on pathogenic E. coli and S. aureus in the intestinal tract and antibiotic tolerance of Lacto-bacillus acidophilus were also studied. The results indicated that Lactobacillus acidophilus survived at pH 2.5 - 4.5 after 6h culture and the living bacterial number could reach 107cfu/mL. One strain even survived at pH 1.5; that living bacterial number were above 106cfu/mL at the 0.1% -0.3% bile salt and a strain survived in 0.4% after 4h culture; that antimicrobial activities to the pathogenic E. coli and 5. aureus were obvious; and that the tolerance to Penicillin and Roxithromycin was medium and power.

Professor LI Zhi-dao, according to acupoint selection of syndrome differentiation in TCM basic theory, concluded a new therapy, namely "tonifying three qi" that is mainly based on three acupoints in the Conception Vessel. This method is consisted of Danzhong (CV 17), Zhongwan (CV 12) and Qihai (CV 6) in the Conception Vessel, which could successively nourish clear qi, stomach qi and original qi. In clinic, according to the severity of symptoms of three qi, the acupoints are selected flexibly, which could respectively treat deficiency of heart-lung qi, deficiency of stomach-spleen qi and deficiency of original qi. Some examples are also given in the article.
Acupuncture Points ; Acupuncture Therapy ; history ; methods ; China ; History, 20th Century ; History, 21st Century ; Humans ; Qi

BackgroundGlaucoma associates with apoptosis of retinal ganglion cells ( RGCs).Research showed that ciliary neurotrophic factor (CNTF) can repair optic nerve trauma,but it has not reported whether CNTF has a protective effect on glaucomatous optic neuropathy.ObjectiveThis experimental study was to explore the protective effect of CNTF on RGCs in rat eyes with acute ocular hypertension.MethodsOcular acute hypertension models were induced in bilateral eyes of 24 clean Wistar rats by forced perfusion of a balanced salt solution into the anterior chamber.Two days before molding,0.5 μg recombinant human CNTF (5 μl) was injected intravitreously in the left eyes,and 5 mmol/L sodium phosphate solution (5 μl) was injected in the same way as the control group.Three other Wistar rats were used as the normal control group.The animals were sacrificed by excessive anesthesia and the retinal sections were prepared 1,3,7,14 days after molding.The morphology of the retina was examined and RGCs counting was performed by hematoxylin & eosin staining and observed under a light microscope.The expression of glutamic acid in RGCs was assessed by immunochemistry.ResultsRegular retinal structure with clearly defined cell layers were observed in normal control rats.Changes in vacuoles in RGCs were seen in the model control group.The number of degenerative RGCs decreased in the CNTF group.Compared with the model control group,number of normal RGCs increased from 1 day to 14 days after molding with a significant difference between the two groups (all P=0.000).Immunochemistry assay showed that the numbers of positive cells for glutamic acid were 5.50±1.04 and 6.00±1.41 for the average of 3 fields at 3 days or 7 days in the CNTF group,and those in the model control group were 9.00±2.91 and 10.83 ± 1.94,respectively,showing significant differences between them ( all P =0.000 ).However,no comparable differences were found in the numbers of positive cells for glutamic acid at 1 day and 14 days between the two groups( P=0.578,0.180).ConclusionsCNTF down-regulates the expression of glutamic acid in RGCs and offers neuroprotection for RGCs in an acute glaucoma rat model.

Objective To investigate the quality of life and its influence factors in patients with atrial fibrillation 3 months after catheter ablation. Methods From April 2014 to February 2016,AF patients who underwent single catheter ablation in our hospital were included. The quality of life was assessed by MOS 36 item short form health survey (SF-36), and the effect of related factors on QOL scores were further analyzed. Results There were no significant changes in quality of life at baseline and 3 months after catheter ablation including physical component summary (PCS) [(70.6±17.1) vs.(72.9±10.7),P =0.078]score, mental component summary (MCS) [(70.9±12.3) vs.(71.8±12.5), P =0.44] score and SF-36 score [(70.8±13.0) vs. (72.3±10.3), P=0.138]. Multivariate analysis indicated that there was negative correlation between patients who relapsed after ablation and better quality of life(PCS, β=―3.162, P=0.036;MCS, β=―5.675, P =0.001; total SF-36 score, β=―4.385, P =0.003), MCS score and warfarin use (MCS,β=―4.020,P =0.014). There was negative correlation between PCS score and smoking(PCS, β=―3.129,P =0.037).Conclusion All patients had stable quality of life in 3 months after catheter ablation. Ablation outcome was probably the main influencing factors. The use of dabigatran and smoking might also have effects on their quality of life.

Objective To explore whether chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction and possible mechanism. Methods Thirty-nine one month old male Sprague-Dawley rats were randomized into sham control group ( C ) , swimming group ( C-S ) , radiation group( R) , and radiation plus swimming group( R-S) . Radiation groups were given a single dose of 20 Gy on whole-brain. Rats in the swimming groups were trained with swimming of 15 min/d, 5 d/w. Rat behavior was performed 3 months after radiation in an order of free activity in an open field and the Morris water maze test including the place navigation and spatial probe tests. Then, the protein expressions of BDNF, P-ERK, T-ERK, P-CREB and T-CREB in the rat hippocampus tissue were assayed by Western blot. Results On the day 2, in the place navigation test of Morris water maze, the latency of swimming group was significantly shorter than that of sham group, the latency of sham group was significantly shorter than that of radiation group, and the latency of radiation swimming group was significantly shorter than that of radiation group(P<0?05). In the open field test, the latencies of the place navigation and spatial probe tests of Morris water maze had no significant difference among four groups (P>0?05). Western blot assay showed that the expressions of BDNF and its downstream signals including P-ERK and P-CREB were markedly reduced by radiation ( P < 0?05 ) , but this reduction was attenuated by the chronic forced swimming stress. Conclusion The chronic forced swimming stress could improve whole brain radiation induced cognitive dysfunction by up-regulating the expressions of BDNF and its downstream signal molecules of P-ERK and P-CREB in hippocampus.

After health information push service on Internet was investigated ,suggestions were put forward for impro-ving the health information service by making use of the Wechat public platform according to the incomplete and non-professional health information service , rampant advertisements and unaccessible personal information on Internet .