Objective To analyze the effect of duloxetine on S100B and signal pathway ERK1/2-NF-κB expression in hippocampus in depression rat.Methods Chronic unpredictable mild stimulation was used to establish depressive model rats (n=50).They were randomly divided into no-intervention group (n=10),different treatment time of duloxetine group (C,D,E,F group,10 rats in each group)and then 10 normal rats were selected as control group.Behavior tests including open-field test and the saccharine preference test were used to test the behavioral change of rats after 28 days intragastric administration.Western blot was used to detect S100B,t-ERK1/2,pERK 1/2,t-NF-κB and pNF-κB expression in hippocampus.Results In open-field test,the crossing score,rearing score and latency of the rats in E,F group were (69.68± 14.61) and (70.66± 11.53) score,(20.94 ± 10.92) and (20.32±8.85) score,(1.1±0.4)s and(1.0±0.4) s respectively,and showed no significant difference with those of control group ((71.19±12.08) score,(20.42±8.76) score,(1.0±0.3)s) after 28 d intragastric administration (P＞0.05),while the level score,vertical score were significantly higher than those in depressive model (P＜ 0.05).In the saccharine preference test,the rats in E,F and control group exhibited increased saccharin preference compared with depressive model rats (P＜0.05).The rats in E,F and control group exhibited increased S100B,pERK1/2 and pNF-κB expression in hippocampus compared with depressive model rats (P＜0.05).Conclusion Duloxetine improves the behavioral ability of depression rat and exerts effect after 2 weeks.The ERK1/2-NF-κB signal pathway in hippocampus may participate in this mechanism.

As a new neuroimaging method, functional magnetic resonance (fMRI) with its importance of data processing has been widely recognized by neurology and cognitive psychology. Focusing on the realignment section in fMRI image preprocessing, this paper comprehensively describes the registration principle of SPM, an internationally-known software package which is specially designed for cerebral function imaging. An improved registration method is presented which effectively increases the accuracy. In addition, choosing the ratio of SSD and NMI as the registration measure can compensate for the limitation of using single measurement, which improves the robustness and reliability of the registration process. Experimental results prove the feasibility of this method.

Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.

AIM: To evaluate the safety, efficacy and stability of posterior chamber phakic intraocular lens ( ICL ) implanation and clear lens extraction for the correction of high myopia.
METHODS: The study enrolled 56 cases ( 100 eyes ) of high myopia. Group I comprised 32 cases ( 58 eyes ) receiving ICL implantation and Group II comprised 24 cases (42 eyes) undergoing clear lens extraction. In this study, we evaluated the two groups of subject's the visual and refractive results, intraocular pressure ( IOP ) , endothelial cell density ( ECD ) , anterior chamber depth ( ACD) , lens transparency, the surgical complications as well as visual adverse symptoms before and after surgery.
RESULTS: The postoperative subjects in group I and group II were followed, uncorrected vision acuity ( UCVA)>0. 5 were 69. 0% in group I and 71. 4% in group II after 3mo. UCVA>0. 5 were 72. 4% in group I and 73. 8% in group II after 1a. Predictability of the manifest spherical equivalent refraction within±1. 00D was achieved in 62. 1%of eyes in group I and 57. 1% in group II after 1a. The central vault of the ICL ( distance from posterior surface of ICL to the crystalline lens ) measured with anterior segment optical coherence tomography ( AS-OCT ) was 0. 35-0. 54 (0. 40±0. 16) mm. Twelve point one percent of eyes in group I and 7. 1% of eyes in group II had transient mild increase in IOP. Here were statistically significant differences between preoperative and postoperative ECD (P<0. 001 ). Complications of surgery: 1 eye had ICL spontaneous rotation, 2 eyes had anterior subcapsular cataract, 4 eyes noticed halos around lights at night in group I. Three eyes had posterior capsule mild opacification, 3 eyes noticed halos around lights at night, 12 eyes had difficulty in near vision in group II.
CONCLUSION: ICL implantation and clear lens extraction are effective, safe and predictable surgical option for the management of high myopia. No severe complications occurred, but its long time effect and safety still need more time to prove.

Objective To evaluate the clinical efficacy of the over-the-scope-clip (OTSC) for endoscopic closure of acute refractory non-variceal upper gastrointestinal bleeding. Methods This retrospective study selected 16 refractory patients, including 2 cases with Mallory-Weiss syndrome, 7 cases with gastric ulcer, 1 case with gastric carcinoma and 6 cases with duodenal ulcer, underwent OTSC treatment of acute non-variceal upper gastrointestinal bleeding from January 2015 to June 2016 as study subjects. Results All of the 16 patients with bleeding lesions were successfully controlled. The successful rate is 100.0%. The mean procedure of OTSC for endoscopic bleeding closure was between 5.0 and 6.0 min. Conclusion The Over-the-Scope-Clip system is safe and effective for closure of acute non-variceal upper gastrointestinal bleeding in refractory patients, and deserves further clinical applications.

[Summary] To determine how endocrinologists in China access and treat patients with Graves' orbitopathy (GO) and gain insight on how to make the management of this disease more uniform and standardized in the context that management of GO continues to be challenging.Based on the questionnaire used in the European survey on GO,a questionnaire in Chinese was drafted and circulated to the members of Chinese Society of Endocrinology (CSE).There were a total of 124 valid responders.The majority (94.4％) of the responders believe that a muhidisciplinary approaches for GO management is valuable.Over 80％ of the participants advocated the evaluation of exophthalmometry,vision,visual fields by perimetry,eye movements,fundoscopy,TSH receptor antibodies,thyroid function,and ultrasound.Steroids were preferred as the first-line therapy by 92.7％ of responders,among them,59.7％ choose intravenous route.The treatment strategy for GO with intravenous glucocorticoids therapy still remains debated.Antithyroid drugs were the most common choice (72.6％) for first-line therapy of thyrotoxicosis.Treatment options for GO were very similar among Chinese,Latin-American,and European responders,though radioactive iodine and surgical treatment were more often indicated in China.The appropriate treatment of the patient with GO is controversial even amongst thyroid specialists.Further training of clinicians,easier access of patients to specialist multidisciplinary centres,and the publication of practice guidelines may help improving the management of this condition in China.

Objectives:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) and identify the risk factors for death.Methods:The clinical data of 60 patients undergoing ECPR admitted to our hospital and Hangzhou First People's Hospital from September 2014 to September 2019 were retrospectively analyzed. The patients were divided into the survival group and the death group. The clinical data of the two groups were compared to explore the risk factors related to death. COX regression analysis was used to identify the risk factors for death.Results:Sixty patients undergoing ECPR were included in our study, of them, 16 (26.7%) cases were out-of-hospital cardiac arrest (OHCA) and 44 (73.3%) cases were in-hospital cardiac arrest (IHCA). The mortality of OHCA patients was higher than that of IHCA patients (87.5% vs. 56.89%, P < 0.05), and the duration from CPR to ECMO installation in the death group was longer than that in the survival group [(105.4±105.1) min vs. (53.0±28.5) min, P < 0.05]. Compared with the survival group, patients in the death group had higher troponin and glutamic oxalacetic transaminase and lower PH and lactate ( P < 0.05). The median survival time of the 60 patients was 42 days. Out-of-hospital cardiac arrest, high SOFA score before ECMO, high-dose norepinephrine, pulmonary infection during ECMO support and long ECMO support time were independent predictors of patients’ death. Conclusions:Risk factors associated with patients’ death undergoing ECPR are out-of-hospital cardiac arrest, high SOFA score before ECMO, high-dose norepinephrine, long duration from CPR to ECMO installation, pulmonary infection during ECMO support and long ECMO support time.

Objective To investigate the risk factors of severe hemolysis during extracorporeal membrane oxygenation (ECMO). Methods The clinical data of adult patients undergoing ECMO after cardiac surgery admitted to Fuwai Hospital from December 2010 to October 2015 were retrospectively analyzed. Demographic characteristics, renal function, primary disease, operation data, ECMO related data and outcomes were recorded. Patients were divided into normal free hemoglobin (FHB) group (FHB ≤ 500 mg/L) and severe hemolysis group (FHB > 500 mg/L) according to the FHB level during ECMO support. The parameters before and after ECMO support were compared between the two groups. Logistic regression was used to identify the independent risk factors of severe hemolysis. Results A total of 81 patients including 19 patients with severe hemolysis was enrolled, and 62 in normal FHB group. There was no difference in cardiopulmonary bypass (CPB) time, clamping time, lactate level before ECMO, cardiopulmonary resuscitation, intra-aortic balloon pump use and central catheter insertion between two groups. The maximums of serum creatinine (SCr) and FHB levels were higher in severe hemolysis group as compared with those in normal FHB group [maximal SCr (μmol/L): 281.02±164.11 vs. 196.67±87.31, maximal FHB (mg/L): 600 (600, 700) vs. 200 (100, 300)], the incidence of clots in circuit or oxygenator, infection, and hemofiltration in severe hemolysis group was increased [26.3% (5/19) vs. 4.8% (3/62), 31.6% (6/19) vs. 12.9% (8/62), 36.8% (7/19) vs. 14.5% (9/62), all P < 0.1]. As well as outcomes including the rate of site of surgery or intubation bleeding and acute renal failure [ARF, 57.9 % (11/19) vs. 30.6% (19/62), 94.7% (18/19) vs. 41.9% (26/62)], and the survival rate was lowered [10.5% (2/19) vs. 51.6% (32/62), all P < 0.05]. As result of univariate analysis, clots in circuit or oxygenator, infection and hemofiltration were associated with severe hemolysis. It was showed by logistic regression analysis that the clots in circuit or oxygenator was a risk factor of severe hemolysis during ECMO [odds ratio (OR) = 6.262, 95% confidence interval (95%CI) = 1.244-31.515, P = 0.026]. Conclusions The clots in circuit or oxygenator were independent risk factors of severe hemolysis during ECMO. Severe hemolysis can induce the increase of the rate of bleeding in the operation site or intubation and the rate of ARF, and decrease of the survival rate.

AIM: To investigate and analyze the changes of corneal biomechanics of normal eyes,forme frusta keratoconus eyes,subclinical keratoconus eyes and clinical keratoconus eyes by Corneal visualization Scheimpflug technology (Corvis ST),and provide clinical basis for early diagnosis of keratoconus.METHODS: Case-control study.We randomly selected 40 normal eyes as normal group,15 forme frusta keratoconus eyes as forme frusta keratoconus group,23 subclinical keratoconus eyes as subclinical keratoconus group,and 40 clinical keratoconus eyes as keratoconus group.The biomechanical parameters of each group were measured by Corvis ST.The receiver operating characteristic(ROC) curves was plotted to distinguish keratoconus from the normal cornea.RESULTS: There was no significant difference in the parameters of biomechanics between normal group and forme frusta keratoconus group (P>0.05).Compared to normal group and subclinical keratoconus group,the parameters second applanation length(AL2),first velocity of applanation (AV1),central curvature radius at highest concavity (HC-radius),deformation amplitude (DA) were revealed statistically significant differences(P<0.05).The biomechanical parameters of the keratoconic group were significantly different from those of normal group except for the second velocity of applanation (AV2),time from the start until the highest concavity(HC-time),peak distance (PD).ROC curve showed that the DA(area under the curve:0.891±0.028) was the best predictive parameter to distinguish keratoconus from the normal eyes.CONCLUSION: The corneal biomechanical parameters of forme frusta keratoconus group are not changed compared with normal group.The changes between normal group and subclinical keratoconus group should combine with other technology to further improve subclinical keratoconic screening.Compared with normal corneas,keratoconus has a great change in biomechanics,which DA diagnosis of the highest efficiency.

Background More and more attentions are paid to the effect of matrix metalloproteinases (MMPs) in the process of wound healing after excimer laser.Objective The present study was to investigate the effects of GM6001,a matrix metalloproteinases inhibitor,on haze formation after excimer laser epithelial keratomileusis (LASIK).Methods LASEK of -10.00 diopter was bilaterally performed on 27 New Zealand white rabbits and then divided randomly into the GM6001 group,Fluorometholone (FML) group and normal control group.Corneal haze was graded under dim light at 2 weeks,4 weeks and 8 weeks after operation,and the number of eyes in different grades of haze were compared among the three groups.Six corneal samples were harvested in each group for confocal microscope examination at 2,4,8 weeks.The corneal histopathological examination was carried out with the optical microscope,and the ultrastructure of the cornea was examined under the transmission electron microscope.Results The numbers of eyes of different corneal grades of haze at 2,4 or 8 weeks after surgery were significantly different among the three groups (P＜0.05).Compared with the normal control group,the corneal haze grades in the GM6001 group and FML group were apparently lower (P＜0.01),but there was no significant difference in the numbers of eyes of different corneal grades of haze between the GM6001 group and FML group (P＞0.01).The numbers of keratocytes in the GM6001 group were apparently lower than those in the normal control group and FML group in 2,4 or 8 weeks after operation (P＜0.05).No significant difference in the keratocytes was seen between the normal control group and FML group at various time points (P＞0.05).Corneal epithelial cell morphology,disordered arrangement of collagen fibers in GM6001 group and in FML group were less pronounced than in the negative control group.Conclusion GM6001 has an inhibitory effect on the formation of corneal haze after LASEK which suppresses proliferation and production of keratocytye with the similar efficacy as FML.