Objective:To explore the effects of apolipoprotein E-mimetic peptide COG1410 on M1/M2 microglia polarization and retinal ganglion cells (RGCs) survival after ischemia-reperfusion (IR) injury in the mouse retina and its possible mechanisms.Methods:Eighteen 8-week-old C57BL/6J male mice were divided into control group (6 mice), IR 3 days group (6 mice), IR 7 days group (3 mice), and IR 14 days group (3 mice) according to the randomized number table method.Mice in IR group were perfused in the anterior chamber using saline, and the intraocular pressure (IOP) was raised to 100 mmHg (1 mmHg=0.133 kPa) and maintained for 1 hour in order to establish a model of IR injury in the retina.Three mice from control group and 3 mice from IR 3 days group were taken to observe the distribution of retinal microglia by immunofluorescence staining of retinal frozen sections.Three mice were taken from normal control, IR 3 days, IR 7 days, and IR 14 days groups respectively to observe the changes of retinal M1-type and M2-type microglial cells with time after IR injury by immunofluorescence staining of retina.Another 91 C57BL/6J mice were randomly divided into normal control group (19 mice), IR group (24 mice), saline group (24 mice), and COG1410 group (24 mice) according to the random number table method.Mice in normal control group maintained a normal IOP, and the IR injury model was established in the other three groups.In addition, COG1410 group and saline group were injected with 1 mg/kg COG1410 and an equal volume of saline by tail vein injection, respectively.The microglia phenotype and survival rate of RGCs were observed by immunofluorescence staining of retinal wholemount.The relative expressions of retinal tumor necrosis factor-ɑ (TNF-ɑ) and interleukin-1β (IL-1β) mRNA were detected by real-time fluorescence quantitative PCR.The apoptosis of retinal neuronal cells was observed by the TUNEL assay.The expression levels of retinal nuclear factor-κB (NF-κB), B lymphocyte-2 (Bcl-2), and Bcl-2-associated X protein (Bax) proteins were detected by Western blot.Use and care of animals strictly complied with the Hubei Provincial Regulations on the Management of Laboratory Animals and the experiment was approved by the Animal Ethics Committee of the Renmin Hospital of Wuhan University (No.WDRM20190113).Results:Retinal microglia in normal control group and IR 3 days group were mainly distributed in the ganglion cell layer, inner plexiform layer, and outer plexiform layer.There were statistically significant differences in the comparison of the proportions of M1-type and M2-type microglia among normal control, IR 3 days, IR 7 days, and IR 14 days groups ( F=29.83, 57.62; both at P<0.001). Compared with normal control group, the number of M1-type microglia was higher in IR 3 days group, and the number of M2-type microglia was higher in IR 7 days group, and the differences were statistically significant (all at P<0.05). The proportions of M1-type microglia in normal control group, IR group, saline group, and COG1410 group were (4.25±0.57)%, (65.26±10.43)%, (63.01±4.93)%, and (33.13±4.46%), respectively, and the proportions of M2-type microglia in the four groups were (4.50±0.20)%, (11.47±0.24 )%, (11.75±0.17)%, and (38.93±4.26)%, showing statistically significant differences among them ( F=23.33, 50.82; both at P<0.001). The proportions of M1-type microglia decreased while the proportions of M2-type microglia increased in COG1410 group when compared with IR group, and the differences were statistically significant (both at P<0.05). There were statistically significant differences in RGCs survival rate, relative expression of retinal TNF-ɑ and IL-1β mRNA, retinal apoptotic cell count, retinal NF-κB and Bax protein expression levels, and Bax/Bcl-2 ratio among the four groups ( F=30.77, 12.52, 6.74, 28.72, 13.02, 7.94, 7.58; all at P<0.05). Compared with normal control group, there were significant decreases in the survival rate of RGCs and increases in retinal apoptotic cell number, TNF-ɑ and IL-1β mRNA expression, retinal NF-κB and Bax protein expression levels, and Bax/Bcl-2 ratio in IR group (all at P<0.05). Compared with IR group, the COG1410 group had increased retinal RGCs survival rate, decreased TNF-ɑ and IL-1β mRNA expression levels, decreased TUNEL-positive cells, decreased NF-κB and Bax proteins expression levels, and decreased Bax/Bcl2 ratio, and the differences were statistically significant (all at P<0.05). Conclusions:Three days after retinal IR modeling, COG1410 promotes the polarization of M1-type microglia to M2-type, inhibits the expression of retinal NF-κB and downstream inflammatory factors, and attenuates the retinal inflammatory response, as well as inhibits the expression of apoptosis-related proteins, which promotes the survival of RGCs.

Objective:To observe and explore the feasibility and effectiveness of platelet-rich fibrin (PRF) membrane packing and air filling in the treatment of refractory macular holes.Methods:A retrospective clinical study. From January 2019 to January 2020, 17 patients with refractory macular hole (17 eyes) who diagnosed in Renmin Hospital of Wuhan University were included in the study. Among them, there were 7 males (7 eyes) and 10 females (10 eyes), with the age of 55.18±7.91 years. All eyes underwent 23G minimally invasive vitrectomy combined with internal limiting membrane stripping and PRF packing, and air filling was performed at the end of the operation. The best corrected visual acuity (BCVA) and optical coherence tomography angiography were performed in all eyes before surgery and at 1 week and 1, 3 months after surgery. The BCVA examination was performed using a international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution visual acuity during statistics. Taking 3 months after surgery was as the time point to judge the efficacy, the changes of BCVA, superficial retinal vascular density (SVD), foveal avascular zone (FAZ) area and central foveal thickness (CFT) before and after surgery were compared. Paired t-test was used to compare the indicators before and after surgery. Results:Among the 17 eyes, there were 6, 7, and 4 eyes with giant macular hole, high myopia macular hole, and recurrent macular hole, respectively; the hole diameter was 723.94±38.30 μm. Three months after surgery, all holes were closed. Compared with before surgery, the BCVA ( t=4.458) and SVD ( t=2.675) increased, and the CFT ( t=6.329) and FAZ area ( t=4.258) decreased at 3 months after surgery, and the differences were statistically significant ( P<0.05). At the last follow-up, there was no complications such as intraocular hypertension and retinal detachment in all eyes. Conclusion:Minimally invasive vitrectomy combined with internal limiting membrane stripping and PRF tamponade in the treatment of refractory macular holes can increase the closure rate, improve visual acuity and retinal blood perfusion.

Ocular neovascularization is a pathological change in various ocular diseases such as diabetic retinopathy, retinopathy of prematurity, central retinal vein occlusion and age-related macular degeneration, which seriously affects patient's vision. β receptors are expressed in conjunctiva, corneal epithelial cells, corneal endothelial cells, extraocular muscles, trabecular meshwork, ciliary muscle, lens and retina. β adrenergic receptor antagonists bind to β receptors to exert anti-angiogenic effects by inhibiting the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1, interleukin-6 and other angiogenic cytokines; reducing macrophage-related inflammatory response; increasing the expression of anti-angiogenic factors. In the treatment of corneal neovascularization, choroidal neovascularization, and retinopathy of prematurity, it can significantly reduce the area of neovascularization and delay disease progression. Co-administration of anti-VEGF drugs can reduce the frequency of administration of anti-VEGF drugs. At effective therapeutic concentrations, β-adrenergic receptor antagonists are well tolerated; they have broader targets than anti-VEGF drugs, which offers new treatment strategies for ocular neovascularization such as corneal, choroidal and retinal neovascularization.

With the development of endoscopic thyroidectomy, the complications of thyroidectomy and the formation of cervical scar are effectively reduced, which are recognized by surgeons and patients.However, with the development of artificial and robot endoscopic thyroid surgery, there are many kinds of operation methods and approaches.Different operation methods and approaches have their own advantages and disadvantages.In the scope of indications, endoscopic thyroidectomy with artificial and robot has the same effect as traditional thyroidectomy, and has a broader application prospect

From four aspects of the social and cultural barriers,the skills and role barriers of medical workers,patient needs and knowledge barriers,and the weakened third person functions in the conflict between doctors and patients,this paper concluded that the old doctor-patient communication mode,the weakening of the trust rela-tionship,the conflict between traditional moral education and modern society characteristics,the lack of communi-cation skills of medical works,the fixation of doctor's identity and role,the diversity of patient's needs,the con-flict between informed consent rights and the mastery of medical information,the weakening functions of third per-son and other barrier factors that affected the smooth communication between doctors and patients.And this paper put forward that in the process of social transformation,both doctors and patients will advance towards common or even shared communication,and the doctor-patient relationship will develop more harmoniously.

Objective To investigate the effect of Danggui buxue decoction on ventricular remodeling and miR-34a expression after myocardial infarction in mice. Methods Mice myocardial infarction model were estab-lished by the left anterior descending coronary artery embolization. Then the mice were divided into Danggui buxue Decoction group and model group. Mice in Danggui buxue decoction group were given Danggui buxue decoction , and mice in the model group were given the equal volume of saline for 8 weeks. Cardiomyocyte apoptosis was detect-ed by TUNEL staining. Myocardial fibrosis was detected by Masson staining. The expression of miR-34a was detect-ed by quantitative PCR and the expression of Sirt1 was detected by Western blot assay. Results Compared with the model group ,the EF value of the mice was significantly improved (P < 0.05),the myocardial cell index decreased(P<0.05),the content of collagen fibers decreased(P<0.05),the expression of miR-34a decreased, but the expression of Sirt1 increased(P<0.05)in Danggui buxue Decoction group. Conclusion Danggui buxue decoction can effectively inhibit ventricular remodeling of mice following myocardial infarction ,which is associated with the suppression of miR-34a and the increase of Sirt1.

After several in -depth investigations on the third party mediation mechanism of "Guangdong mode" in Guangdong Harmony Medical Dispute Mediation Committee and combined with the analysis of the domes-tic and foreign medical dispute disposal experience , this paper summed up five points that successful construction of harmonious mediation mechanism should grasp .The five points include the fairness of harmonious mediation thoughts , the feasibility of harmonious mediation paths , the justice of harmonious mediation mechanism , the suita-bility of harmonious mediation environment and the success of harmonious mediation results .Only when grasp these five points, couldit create a gradually harmonious doctor -patient relationship .

The credibility of the third-party mediation agencies in medical disputes lies in their own advantages of efficiency,neutrality,professionalism and objectivity.However,because of the differences of actual operation,the credibility of the third-party mediation agencies often is questioned by both doctors and patients and the public.Aiming at these,this paper would study the status and the pushing approach of the third-party mediation agencies credibility from the perspective of professionalism and neutrality,legislation,fundraising channels and supervision.

Objective To explore the expression of miroRNA-21 (miRNA-21) in myocardial fibroblasts stimulated by indoxyl sulfate (IS) and its role on paracrine factors of myocardial fibroblasts.Methods Myocardial fibroblasts which derived from C57BL/6J mice were divided into control group and IS group,and their expressions of miRNA-21 were detected by real time PCR after 48 h.MiRNA-21 inhibitor transfection was applied to silence miRNA-21 expression.Myocardial fibroblasts were divided into creatinine (Scr) group (Scr treated for 48 h),Scr+IS group (Scr and 50 μmol/L IS treated for 48 h),Scr+miRNA-21 inhibitor group (miRNA-21 inhibitor treated for 24 h and then Scr treated for 48 h) and Scr+miRNA-21 inhibitor+ IS group (miRNA-21 inhibitor pretreated for 24 h and then Scr and IS treated for 48 h).Enzyme-linked immunosorbent assay was performed to evaluate the expressions of interleukin-1 (IL-1),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α).Western blotting was applied to detect the expressions of transforming growth factor-β (TGF-β),matrix metalloproteinases 2 (MMP2),matrix metalloproteinases 9 (MMP9) and tissue inhibitor of metalloproteinases 1 (TIMP1).Results The expression of miRNA-21 was obviously increased in IS group than that in control group (P ＜ 0.01).Compared with those in Scr group,the expressions of IL-1,IL-6,TNF-α,TGF-β,MMP2 and MMP9 significantly increased (all P ＜ 0.05),while the expression of TIMP1 decreased (P ＜ 0.05).When the expression of miRNA-21 was inhibited,the expressions of IL-1,IL-6,TNF-α,TGF-β and MMP2 in Scr+miRNA-21 inhibitor+IS group significantly decreased than those in Scr+IS group (all P ＜0.05),and the expression of TIMP1 decreased further (P ＜ 0.05).Conclusions IS can promote the expression of miRNA-21 in myocardial fibroblasts.MiRNA-21 plays an important role in regulating inflammatory factors and pro-fibrogenic cytokines in myocardial fibroblasts.

Objective:To put forward some suggestions for the national health development in the filed of health expenditure indicators .Methods:Two health expenditure indicators and four health outcomes indicators were chosen from WB and WHO official websites , and researches on the relationship between health expenditure and outcomes were conducted .We put forward proposed value of the health cost indicator .Results: With different levels of GDP per capita , the scatter diagram of health expenditure and GDP per capita had different rules .When health outcomes were taken into consideration , the rules were the same .When GDP per capita was at different level , better health outcomes were not related to higher health expenditure .Input-output ratio should be taken into consideration fully . Suggestions:The study should be dynamic as GDP develops .More factors can be added in the research , if the data of the factors is available .In this study , the GDP per capita was divided into 4 sections .The division standard of the GDP per capita can be more delicate .What is more important for the development of health expenditure is not contin-uing input , but better input-output ratio because of diminishing of marginal returns .One set of standards cannot be a-dapted to all countries and districts .We should give full consideration to the improvement of people's health instead of increasing input because the ultimate goal is the former .