The introduction of anti-vascular endothelial growth factor (VEGF) therapy represents a landmark in the management of wet age-related macular degeneration (AMD).However,as a new therapy,several problems such as durability of the therapeutic effects,medication side effects,and medication selection have emerged.We should make appoint of improving the therapeutic effect and safety by realizing the limitation of the therapy,monitoring the clinical potential adverse reactions of anti-VEGF agents,and recommending individualized treatment.

Objective To investigate the role of bone marrow-derived cells (EMC) plays in choroidal neovascularization (CNV).Methods Green fluorescent protein (C-FP) chimeric mice were built by transplanting BMC from GFP transgenic mice to adult wild type C57BL/6J mice.Retinal laser photocoagulation was used to induce CNV in the chimeric mice (treated group) and adult wild type mice (control group).Four weeks later,choroidal flatmount was prepared to detect GFP positive BMC expression in the CNV lesions,and immunofluorescence stain was used to determine the expression of vascular endothelia growth factor (VEGF) and basic fibroblast cell growth factor (bFGF).Results Twenty-nine days after photocoagulation lots of GFP positive BMC presented in the CNV area,which accounted approximate 16.22% of the total CNV area.Some BMC in the CNV area expressed VEGF and bFGF.Conclusions BMC may play an important role in CNV by forming new vessles and secreting angiogenic factors.

Clinician-scientists are doctors who perform laboratory-based or clinically oriented research and have direct patient contact.Not only do they play a critical role in the research and practice of translational medicine,but also they are the educators of the next generation of clinician-scientists.However,clinician-scientists are vanishing.It is urgent to train new clinician-scientists who can be engaged in clinic work,research,and also education.Thus,in order to correct understand the importance of the work of clinical scientists,from multi angle analysis of clinical scientists training problems that may be encountered in the process,the active improvement of the education system and condition,and sustained and efficient guidance to the outstanding seedlings are advocated.Besides,aspiring candidates are also encouraged to seek ideal guidance and support through their career,arrange their work reasonably,strengthen their cooperation and the management ability,and strive to grow into excellent clinician-scientists.

Background Matrix metalloproteinases (MMPs) play important roles in the formation of choroidal neovascularization (CNV),but its mail origin is not ocular cells in situ.Bone marrow-derived cells (BMCs) participate in the formation of CNV and is probably a primary source of expressing MMPs in CNV.MMP-2/MMP-13 is speculated to be the regulating target genes of miR188-5p.Objective This study was to verify whether BMCs are the main source of MMPs,and whether the MMP-2/MMP-13 expression is potentially regulated by miR188-5p.Methods BMCs expressed green fluorescent protein (GFP) from transgenic female C57BL/6J mice were transplanted to female wild-type C57BL/6J mice to establish C57BL/6J.GFP chimeras models,and 42 mice with chimerisms more than 85％ by flow cytometry were included as the experimental group.Other 42 wild-type C57BL/6J mice without the BMCs transplantation were enrolled as the control group.CNV was induced by laser coagulation of retinas on the mice of both groups.MMP-2/MMP-13 levels in the retinochoroid tissue were quantified by ELISA at day 1,3,5,7,10,14,and 28 after photocoagulation.The expression of miR188-5p mR NA in the retinochoroid tissue was assayed by real-time quantitative PCR (RT-qPCR).Immunofluorescence stain and fluorescent in situ hybridization were used to identify the MMP-2/MMP-13 and miR188-5p expressed by GFP-positive BMCs in CNV,and the expression level was quantified by images analysis.Results The proportion of GFP+ mouse mononuclear cells was (90.67±3.02) ％ in the C57BL/6J.GFP chimeras.The concentration changes of MMP-2/MMP-13 in retinochoroid homogenate showed a same tendency with the lapse of time between the experimental group and the control group (MMP-2:F=0.060,P =0.810 ; MMP-13:F =0.012,P =0.915).The expression level was zoomed in retinochoroid tissue after induce of CNV with the maximal value on the third day in both groups,and the proportion in the experimental group was 64.21％ ;while the expression level of MMP-13 was slowly raised after induce of CNV with the peak at the seventh day,and the proportion in the experimental group was 79.61％.A complementary association point of miR188-5p was exhibited in the 3 '-untranslated regions of MMP-2 or MMP-13 by target gene prediction.The expression level of miR188-5p mRNA in the BMCs of CNV area was sharply declined after induce of CNV with the lowest value on the seventh day.A negative correlation was found between the expressing level of miR188-5p and MMP-13 protein (r=-0.868,P＜0.05) as well as early stage of expression level of MMP-2 protein (r=-0.997,P＜ 0.05).Conclusions The elevation of MMP-2/MMP-13 expression levels is associated with the formation of CNV,and the regulation of miR188-5p expression in the BMCs of CNV area is responsible for increase of MMP-2/MMP-13 expression.The tendency of miR188-5p expression is inversed with MMP-2/MMP-13.

Objective To investigate the effects of low-dose X-ray radiation on pituitary gland area to treat benign prostatic hyperplasia.Methods Using the linear-accelerator 6mV X-ray to radiation on pituitary gland area,1.2Gy/f,2 times/week,total dose was 4.8～6.0Gy.The uro-flow rate and residual urine volume were measured.Results The immediate effect was 77.5%,the 1-year effect rate was 70%.After treatment,the uro-flow rate was significantly increased(P

14 aged patients received radiofrequency current ablation(RFCA)to treat drug-refractory tachycardia. The success rate was 97%(13/14).In conjunction with the charcteristicaof aged patients often with long clinical history and apt to be complicated,the paper especially discussed the distinctive feature of application of RFCA to aged patients.

Objective To study the effects of stratum corneum on the percutaneous absorption of fluorescein sodium (NaFl) liposome in rat skin. Methods Stratum corneum was stripped off by Scotch adhesive tape, and the NaFl content in the stratum corneum and the skin with no stratum corneum were detected by spectrofluorimetry at regular intervals. The dynamic permeated amount of different preparations of NaFl in the skin at different intervals in Franz diffuse cell was determined and the distribution of NaFl at 4 h after stripping off the stratum corneum was observed by fluorescence microscope. Results The concentrations of NaFl in the stratum corneum and the skin with no stratum corneum after applying liposome NaFl preparation were significantly higher than those of NaFl solution and gel preparations (P 0.05). Conclusions It is suggested that liposome can increase and change the penetration of NaFl into the stratum corneum and the skin with no stratum corneum in vitro. Hair follicular structure may not play an important role in the drug diffusion when stratum corneum is removed.

Objective To study the effect of Shenlingbaizhu Pills on hyperlipidemia and gut microbiota in guinea pigs, providing data support for the treatment of hyperlipidemia from the " spleen" . Methods Guinea pigs were randomly divided into control group, model group, ezetimibe group, Shenlingbaizhu Pills high and low dose groups, with 12 guinea pigs for each group. Guinea pig models of hyperlipidemia were established with high fat diet for 8 weeks. Oral administration of the drug began at the fifth week and continued for 4 weeks. The serum lipid levels of guinea pigs were determined after final administration. The pathological changes of liver tissue were observed by HE staining. The mRNA expression levels of ATP binding cassette ( ABC ) A1 in liver, Niemann Pick C1 like 1 ( NPC1L1) and ABCG5/8 in small intestine were detected by realtime PCR. 16S rDNA sequencing was used to detect changes of gut microbiotas in guinea pigs. Results Shenlingbaizhu Pills significantly reduced the serum triglyceride, total cholesterol, and low density lipoprotein-cholesterol levels in guinea pigs with hyperlipidemia ( P＜0. 01 or P＜0.05). The pathological degree of fatty liver was improved obviously by Shenlingbaizhu Pills. Shenlingbaizhu Pills could reduce the mRNA expression level of NPC1L1 of small intestine and increase the level of liver ABCA1 and small intestine ABCG5/8 (P＜0.01 or P＜0.05). At the phylum level, Shenlingbaizhu Pills could reduce the proportion of verrucomicrobia of guinea pigs in model group (P＜0.01); At the genus level, Shenlingbaizhu Pills could increase the proportions of erysipelotrichaceae＿unclassified, ruminococcus＿1, and ileibacterium of guinea pigs in model group (P＜0. 01 or P＜0. 05 ), reduce the proportion of akkermansia and eubacterium＿coprostanoligenes＿group ( P＜0.01). Conclusion Shenlingbaizhu Pills had significantly therapeutic effect on hyperlipidemia, and its specific mechanism was related to the regulation of cholesterol transport and intestinal flora.

Objective:To analyze the differences in 18F-fluorodeoxyglucose (FDG) PET/CT imaging and preoperative localization between patients with temporal lobe epilepsy (TLE) and extratemporal epilepsy (ETLE) caused by focal cortical dysplasia (FCD). Methods:From April 2015 to August 2018, a total of 71 patients (45 males, 26 females, age (24.3±9.1) years) with refractory epilepsy who underwent 18F-FDG PET/CT imaging before surgery and confirmed as FCD by pathology in Xuanwu Hospital were retrospectively analyzed. Patients were divided into TLE and ETLE groups based on pathological results. 18F-FDG PET/CT images were analyzed qualitatively and compared with the operation result, then region of interest (ROI) was used to calculate the asymmetry index (AI), and evaluated the hypometabolism of every cerebral region by |AI| semi-quantitatively. Engle classification were followed-up after surgery. Independent-sample t test and χ2 test were used to analyze data. Results:Of 71 FCD patients, 35 were TLE and 36 were ETLE. The onset age of ETLE patients were younger than TLE patients ((10.1±6.5) vs (14.9±9.7) years; t=2.48, P=0.02). In TLE group, 54.29%(19/35) were completely consistent with the operation results, and 42.86%(15/35) showed hypometabolized brain regions in extratemporal lobe. In ETLE group, 27.78%(10/36) were completely consistent with the operation results, and 47.22%(17/36) showed hypometabolized brain regions in temporal lobe. There were significant differences in the lateral accuracy and positioning accuracy of 18F-FDG PET/CT between TLE and ETLE patients (97.14%(34/35) vs 75.00%(27/36), 54.29%(19/35) vs 27.78%(10/36); χ2 values: 7.19, 6.27, both P<0.05). There was no significant difference in |AI| values between the brain regions of TLE and ETLE patients ( z values: from -1.25 to -0.06, all P>0.05). Conclusion:The lateral accuracy and positioning accuracy of 18F-FDG PET/CT in TLE patients are better than that in ETLE patients.

Objective This study was to evaluate the relative applicability of serum cystatin C(Cys C)-based formulas and serum creatinine-based formulas for renal glomerular filtration rate(GFR) of Chinese children with chronic kidney disease(CKD).Methods Six hundred and nine Chinese CKD patients of less than 18 years old were enrolled from January 2011 to October 2016 in Shengjing Hospital of China Medical University.The value for estimated GFR (eGFR) was derived from using the 11 formulas,and 99mTc-DTPA renal dynamic imaging was the golden standard of standard GFR(sGFR).SPSS 22.0 statistical software was used to compare the accuracy of each assessment formula and the correlation between GFR markers(Cys C, β2-MG) and sGFR.Results A total of 609 children were enrolled,including 332 patients in CKD stage 1 (211 males and 121 females),165 patients in CKD stage 2(99 males and 66 females),70 patients in CKD stage 3(43 males and 27 females),22 patients in CKD stage 4(13 males and 9 females),and 20 patients in CKD stage 5(16 males and 4 females).All of the formulas either overestimate or underestimate GFR in chil-dren with CKD. In contrast with other formulas,CKD-EPI formula and Filler formula performed better regardless of gender and age difference.Serum β2-MG and serum Cys C all showed a negative relationship with sGFR(respectively r= -0.478 and r= -0.585,P<0.01).Conclusion CKD-EPI formula and Filler formula provide the better approximation to sGFR than other formulas in Chinese children with CKD.Howev-er,we need to try our best to enroll more patients to develop a more accurate GFR estimation formula in Chinese children.