Polymeric micelles have exhibited attractive properties as drug carriers, such as high stability in vivo and good biocompatibility, and been successfully used to dissolve various drugs of poor aqueous solubilities. In this study, we developed a new type of polymeric micelles with mannose-mediated targeting and pH-responsive drug release properties for anticancer drug delivery. The polymeric micelles were prepared from an amphiphilic polymer, poly (glycidyl methacrylate)-g-mannose (PGMA-Mannose). An anticancer drug, doxorubicin (DOX), was encapsulated into the micelles during the micellization, and could be released rapidly under acidic condition. The specificity of cellular uptake of the micelles by two different cell lines was studied using confocal laser scanning microscopy and the MTT assay. DOX-loaded micelles were efficiently trapped by mannose-receptor-overexpressing cancer cells MDA-MB-231, whereas mannose- receptor-poor cells HEK293 showed much lower endocytosis towards the micelles under the same conditions. Thus, DOX-loaded micelles displayed higher cytotoxicity to MDA-MB-231 cancer cells as compared with free DOX. The present study demonstrates that PGMA-Mannose micelles are a promising targeted drug delivery system for cancer therapy.
Cell Line, Tumor ; Doxorubicin ; pharmacology ; Drug Delivery Systems ; HEK293 Cells ; Humans ; Lectins, C-Type ; metabolism ; Mannose ; chemistry ; Mannose-Binding Lectins ; metabolism ; Micelles ; Receptors, Cell Surface ; metabolism

Objective To investigate the effect of metoprolol and metoprolol combined with moderate inten-sity aerobic exercise on the sympathetic vasoconstriction response of skeletal muscle, functional sympatholysis and the exercise capacity of hypertensive men. Methods Thirty men with mild ( stage 1) essential hypertension were divi-ded into a drug group and an observation group. The drug group received only metoprolol while the observation group took metoprolol and performed aerobic exercise (intensity 50-70％ of VO2max, 30-45 min/time, 3-5 times/week) for 12 weeks. Before and after the experiment, the subjects' maximum oxygen uptake (VO2max), peak power (PP) as well as a rating of perceived exertion ( RPE) curve during exercise were determined using the graded exercise test. Forearm vascular conductance ( FVC) induced by the cold pressor test was measured using Doppler ultrasound at rest and during a handgrip exercise. Sympathetic vasoconstriction response was manifested by the rate of change in the conductance (％FVC) before and after the cold pressor test. Functional sympatholysis ( the ability of muscle contrac-tions to inhibit sympathetic vasoconstrictor response) was quantified using the difference in the ％FVC values (△％FVC) between the handgrip exercise and at rest. Results After the treatment,％FVC during the handgrip exercise was lower than at rest in the observation group.△％FVC had increased significantly, as had VO2max and PP. The RPE curve during a graded exercise test shifted to the right in the observation group, but there was no significant change in the other observations. In the drug group, PP had decreased significantly and the RPE curve had shifted to the left. Conclusion Metoprolol can better improve functional sympatholysis and enhance exercise capacity when it is com-bined with moderate intensity aerobic exercise. That will alleviate any exercise intolerance in men with mild hyperten-sion caused by taking metoprolol alone.

Ophthalmology is interrelated with a variety of disciplines, and its features determine the need for interdisciplinary joint training of postgraduate students majoring in ophthalmology. The joint training can optimize the students' knowledge structures, enhance their innovation abilities and improve their overall qualities. However, there are still some factors restricting the interdisciplinary joint training in the existing education system. We propose to establish a full-time administrative management system, build a multidisciplinary communication platform, attach great importance to tutors' interdisciplinary researches, and establish dual mentor or multi-tutor training system. Moreover, a reasonable interdisciplinary evaluation system and various incentive mechanisms are advocated to improve the quality of postgraduate education in ophthalmology.

Objective:To explore the correlation between the semiquantitative score of bone ultrasound and the WOMAC OA index in knee osteoarthritis.Methods:From March 2017 to December 2018, 118 patients with knee osteoarthritis diagnosed and treated in Taizhou Hospital of Traditional Chinese Medicine were selected in the research.The patients' bone erosion, joint effusion, synovium hyperplasia and meniscus were evaluated by ultrasound semiquantitative scoring system.Osteoarthritis index of the patients was investigated at the same time.The correlation between the semiquantitative score of myoskeletal ultrasound and WOMAC OA index in knee osteoarthritis was analyzed.Results:In 118 patients with knee osteoarthritis, the semiquantitative scores of myoskeletal ultrasound of bone erosion was (2.33±0.37)points, joint effusion was (2.05±0.26)points, synovial hyperplasia was (2.24±0.15)points, abnormal meniscus position was (1.67±0.28)points, meniscus shape and signal was (1.15±0.14)points.The WOMAC OA index scores of patients' pain was (29.52±6.68)points, stiffness was (11.43±3.78)points, dysfunction was (93.85±18.73)points, and total score was (134.80±29.19)points.The scores of bone erosion, joint effusion, synovium hyperplasia and meniscus in semiquantitative score of muscle and bone ultrasound were positively correlated with the total score of WOMAC OA index( r=0.435, 0.317, 0.429, 0.294, 0.282, all P<0.05). Conclusion:Semiquantitative score of muscle and bone ultrasound can better reflect the degree of knee joint injury, which is positively correlated with WOMAC OA index.We can use the semiquantitative score of muscle and bone ultrasound and WOMAC OA index to predict the condition of patients with knee osteoarthritis.

Objective To evaluate the prognostic value of a novel prediction model based on fibrinogen concentration in combination with neutrophil-to-lymphocyte ratio (F-NLR score) in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant therapy and investigate their relationship with pathologic complete response (pCR).Methods Clinical data of 218 eligible ESCC patients treated with neoadjuvant therapy in the Affiliated Cancer Hospital of Zhengzhou University between 2012 and 2015 were retrospectively analyzed.The cut-off values for fibrinogen and neutrophil-to-lymphocyte ratio (NLR)were defined by the receiver operating characteristic (ROC) curve.The effects of different F-NLR scores on survival and pCR were evaluated.The survival rate was analyzed using the Kaplan-Meier method.The relationship among fibrinogen,NLR and pCR was analyzed by using Wilcoxon rank sum test.Results The 3-year overall survival (OS) rates with F-NLR scores of 0,1 and 2 were 72.1％,66.5％ and 50.2％(P=0.010),respectively.The corresponding 3-year disease-free survival (DFS) rates were 64.1％,60.2％ and 45.4％ (P=0.012),respectively.The clinical prognosis of patients with an F-NLR score of 2 was significantly worse compared with those of their counterparts with an F-NLR score of 0-1 (P=0.003).Multivariate analysis demonstrated that the F-NLR score (P=0.004) and TNM stage (P=0.000) were the independent prognostic factors.Conclusions The F-NLR score can be used as an independent prognostic factor for ESCC patients treated with neoadjuvant therapy,which is promising supplement to current TNM staging system,thereby facilitating more accurate risk stratification analysis and achieving individualized multidisciplinary treatment for ESCC patients.

Objective To study effects of different types of high-impact exercises on the increment of bone mineral density (BMD) and bone mineral content (BMC) . Methods Thirty-nine male volunteers, including 13 hoopsters, 13 paratroopers, and 13 common college students as the control, were recruited and divided into two subgroups (subgroup 1:20-22 years old; subgroup 2:23-25 years old). Their BMDs and BMCs on calcaneus, first through fifth metatarsus, hip, and lumbar spine (L1-4) were evaluated. Results The BMC of calcaneus, the first and second metatarsals, total lumbar spine, and total hip in the hoopster group was significantly higher than that in the control group and paratrooper group. The hoopster group obtained statistically higher BMD at the lumbar spine, hip, and femoral neck than the other two groups. However, the BMCs and BMDs of the paratrooper group and control group had no significant differences at almost all measured anatomical locations. Conclusions BMC and BMD are not always in positive correlation with vertical ground reaction forces during normal exercises. Compared with parachuting training, playing basketball as a kind of variable load exercise can effectively increase BMC and BMD, and is more beneficial for reducing the risk of osteoporotic fracture.

Objective:A multi-center and large sample volume study was conducted on the verification and improvement of the early established criteria for intelligent routine urinalysis validation (including the microscopic review rules and manual validation rules, referred to as intelligent criteria for short), in order to improve the clinical application of this intelligent criteria.Methods:A total of 31 456 urine specimens were collected from the inpatients and outpatients in six hospitals in China, from March to September 2019. Firstly, 3105 specimens were analyzed for preliminary verification and improvement of the intelligent criteria based on the results of the microscopic examination and manual validation. Secondly, 28 351 specimens were used to verify the clinical application of the improved intelligent criteria. All samples were manually validated as reference.Results:The approval inconsistency rate of the manual validation rules in the original intelligent criteria was 8.59% (202/2 352), and the interception inconsistency rate was 8.84% (208/2 352). The false negative rate and the microscopic review rate of the microscopic review rules were similar to the previous results. Based on an in-depth analysis of big data and the discussions by senior technicians from eight hospitals, one microscopic review rules and four manual validation rules were added, meanwhile two manual validation rule was deleted. The manual validation standards were unified. Finally, the intelligent criteria was improved. Based on the improved intelligent criteria, for microscopic review rules, the false positive rate, false negative rate (misdiagnosis rate), and microscopic review rate did not change significantly, which were 14.72% (457/3 105), 4.06% (126/3 105), and 24.73% (768/3 105), respectively. The approval inconsistency rate and the interception inconsistency rate of manual validation rules were both reduced to 0; the total manual validation rate of the intelligent criteria was 50.89% (1 580/3 105), and the auto-validation rate was 49.11% (1 525/3 105). The large sample volume verification results were consistent with the preliminary verification results of the improved intelligent criteria.Conclusion:This multi-center and large sample volume study had shown that the improved intelligent criteria had better clinical performance.