Objective To compare the postoperative effect of pars plana vitrectomy,phacoemulsification and intraoeular lens (IOL)implantation with silicon oil removed,phacoemulsification and IOL implantation.Design A retrospective case-control study.Par- ticipants 91 cases(104 eyes)of proliferative diabetic retinopathy with tractive retinal detachment or vitreous hemorrhage were per- formed cataract surgery with IOL implantation.Methods All patients were followed up average 6 months,in whom 52 eyes with pars plana vitrectomy,phacoemulsification and IOL implantation(combined group),and the other 52 eyes with silicon oil removed,pha- coemulsification and IOL implantation(sequential group).The differences of the postoperative visual acuity and inflammatory reactions of the anterior chamber between the two groups were analyzed.Main outcome measures Visual acuity and inflammatory reactions of the anterior chamber.Results There were 14/52 eyes with best corrected visual acuity more than 0.1 in combined group and 8/52 eyes in the sequential group after the surgeries(X~2=-6.87,P=0.07) .Corneal edema happened in 16/52 eyes in combined group and 6/52 eyes in sequential group 1 week after the surgeries(X~2=11.53,P=0.001).Keratic precipitate happened in 20/52 eyes in combined group and 9/52 eyes in sequential group after the surgeries(X~2=5.79,P=0.019) .Conclusions The incidence of postoperative anterior chamber in- flammation is higher in Phacoemulsification combined with pars plana vitrectomy group.

Asian Continental Ancestry Group ; Humans ; Language ; Medicine, Chinese Traditional ; Translations

The coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which has led to serious worldwide economic burden. Due to the continuous emergence of variants, vaccines and monoclonal antibodies are only partial effective against infections caused by distinct strains of SARS-CoV-2. Therefore, it is still of great importance to call for the development of broad-spectrum and effective small molecule drugs to combat both current and future outbreaks triggered by SARS-CoV-2. Cathepsin L (CatL) cleaves the spike glycoprotein (S) of SARS-CoV-2, playing an indispensable role in enhancing virus entry into host cells. Therefore CatL is one of the ideal targets for the development of pan-coronavirus inhibitor-based drugs. In this study, a CatL enzyme inhibitor screening model was established based on fluorescein labeled substrate. Two CatL inhibitors IMB 6290 and IMB 8014 with low cytotoxicity were obtained through high-throughput screening, the half inhibition concentrations (IC₅₀) of which were 11.53 ± 0.68 and 1.56 ± 1.10 μmol·L^-1, respectively. SDS-PAGE and cell-cell fusion experiments confirmed that the compounds inhibited the hydrolysis of S protein by CatL in a concentration-dependent manner. Surface plasmon resonance (SPR) detection showed that both compounds exhibited moderate binding affinity with CatL. Molecular docking revealed the binding mode between the compound and the CatL active pocket. The pseudovirus experiment further confirmed the inhibitory effects of IMB 8014 on the S protein mediated entry process. In vitro pharmacokinetic evaluation indicated that the compounds had relatively good drug-likeness properties. Our research suggested that these two compounds have the potential to be further developed as antiviral drugs for COVID-19 treatment.

Transmembrane serine protease 2 (TMPRSS2) is a cell surface protease widely present in the human body. It is involved in the infection of various viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the cell invasion, tumor growth and metastasis processes of prostate cancer. This study used Boc-Gln-Ala-Arg-AMC as the fluorescent substrate to determine the cleavage activity of TMPRSS2 towards SARS-CoV-2 S protein. Then cell-based screening model for TMPRSS2 inhibitors was established in Vero E6 cells overexpressing TMPRSS2 (Vero E6/TMPRSS2). Seven compounds exhibiting TMPRSS2 inhibitory activities with low toxicity were obtained through high-throughput screening (HTS) from natural and synthetic compound pure product library of National Center for Screening Novel Microbial Drugs. Surface plasmon resonance (SPR) has shown that the obtained inhibitors could bind to TMPRSS2 with moderate affinity in a dose dependent manner. Cell-cell fusion experiments have shown that the obtained inhibitors can inhibit the occurrence of S protein mediated cell-cell fusion by inhibiting TMPRSS2 cleavage of SARS-CoV-2 S protein in a concentration dependent manner. Preliminary pseudovirus experiment showed that the inhibitors may reduce the pseudovirus infection into Opti-HEK-293T-ACE2 cells to varying degrees. In a word, this study successfully established a cell-based HTS model for TMPRSS2 inhibitor and preliminarily confirmed that the seven screened inhibitors possessed in vitro anti-TMPRSS2 activities, providing new structural scaffolds for the development of new drugs against SARS-CoV-2.

Objective To investigate the prevalence and clinical significance of different subtypes (IgG,IgM and IgA) of anticardiolipin antibodies (aCL) and anti-β2-glycoprotein Ⅰ antibodies (aβ 2GP1),as well as lupus anticoagulant (LA) in systemic lupus erythematosus (SLE).Methods IgG/IgM/IgA,IgG,IgM,IgA aCL and anti-β2GP1 were tested by enzyme-linked immunosorbent assay (ELISA) in 100 patients with SLE (42 patients were diagnosed as secondary antiphospholipid syndrome),44 healthy controls and 32 patients with other connective tissue diseases excluding SLE and antiphospholipid syndrome (APS).Meanwhile,LA was tested by modified Dilute Russell's viper venom time (dRVVT).The correlation between antiphospholipid antibodies and clinical manifestation was analyzed by Spearman correlation analysis.The postiverate of antiphospholipid antibodies in SLE patients,health controls and patients with other connective tissue diseases were compared by chi square test.The concentrations of antiphospholipid antibodies in different groups were compared using independent sample Kruskal Wallis test.The diagnostic efficacy of antiphospholipid antibodies in SLE patients was analyzed by crosstable using clinical diagnosis of APS as gold standard.P ＜ 0.05 was considered statistically significant.Results The prevalence of IgG aCL (x2 =15.031,P ＜ 0.001),IgA/G/M (x2 =11.678,P =0.003) and IgA (x2 =6.17,P =0.036) antiβ2GP1 were significantly higher in patients with SLE than in the other two groups.IgA/G/M (r =0.207,P=0.039),IgG (r=0.230,P=0.021) and IgA (r=0.217,P=0.030) aCL,IgA/G/M (r=0.218,P=0.029) and IgA (r =0.255,P =0.01) anti-β2GP1,as well as LA (r =0.233,P =0.02) were associated with thrombotic events.IgA/G/M anti-β2GP1 (r =0.22,P =0.029) and LA (r =0.254,P =0.011) were associated with pathological pregnancy.23.1％ (6/26) aCL positive SLE patients were IgM and/or IgA aCL positive.53.6％ (15/28) anti-β2GP1 positive SLE patients were IgM and/or IgA antiβ2GP1 positive.In SLE patients,the specificity and sensitivity of IgA/G/M aCL for APS were 98.3％ and 26.2％,respectively.The specificity and sensitivity of IgA/G/M anti-β2GP1 were 84.5％ and 40.5％,respectively.The specificity of at least two isotypes positive for APS (both aCL and anti-β2GP1 were 98.3％),was higher than IgG aCL (94.8％) or anti-β2GP1 (93.1％).The sensitivity of at least one isotype of aCL (47.6％) or anti-β2GP1 (42.9％) positive for APS were higher than IgG aCL (40.5％)and anti-β2GP1 (21.4％).Conclusions IgG and IgM aCL together would be better than IgA/G/M aCL for APS screening.IgA/G/M anti-β2GP1 would be better for APS screen due to higher sensitivity and strong association with thromboembolic events and pathologic pregnance.IgA aCL or anti-β2GP1 was associated with thromboembolic events.IgA aCL or anti-β2GP1 would be useful for APS diagnosis in IgG and IgM aCL or anti-β2GPl negative patients.

Objective:To investigate the expressions of miR-20a-5p and lysine (K) demethylase 6B (KDM6B) in osteosarcoma tissues and the effects of miR-20a-5p targeting KDM6B on the proliferation, migration and invasion of osteosarcoma cells and tumor growth.Methods:The clinicopathological and paracancerous tissues of 20 patients with osteosarcoma admitted to the First Affiliated Hospital of Chinese Medical University from January 2017 to March 2019 were collected. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miR-20a-5p and KDM6B mRNA in tissues. The osteosarcoma MG63 cells were divided into control group, mimic NC group, miR-20a-5p mimic group, and NC+ empty vector group, miR-20a-5p+ empty vector group, miR-20a-5p+ KDM6B group. The expression levels of miR-20a-5p and KDM6B mRNA of all groups were detected by qRT-PCR. Western blotting was used to detect the expression level of KDM6B. CCK-8 assay, cell scratch test and Transwell test were used to detect cell proliferation, migration and invasion ability. According to the random number table method, nude mice were divided into NC+ empty vector group, miR-20a-5p+ empty vector group and miR-20a-5p+ KDM6B group, with 5 mice in each group. Tumor growth ability was detected by tumor xenograft nude mouse models.Results:The relative expression level of miR-20a-5p mRNA in osteosarcoma tissues was 0.55±0.27, and that in paracancerous tissues was 1.22±0.28, with a statistically significant difference ( t=7.701, P<0.001). The relative expression level of KDM6B mRNA in osteosarcoma tissues was 1.66±0.19, and that in paracancerous tissues was 1.00±0.15, with a statistically significant difference ( t=12.219, P<0.001). After transfection of miR-20a-5p, KDM6B mRNA and protein expression levels decreased with the increase of miR-20a-5p expression level. After miR-20a-5p transfection for 48 h, the cell proliferation abilities of the blank control group, mimic NC group and miR-20a-5p mimic group were 0.83±0.04, 0.81±0.03 and 0.52±0.01 ( F=89.655, P<0.001), compared with the blank control group and mimic NC group, the cell proliferation ability was significantly inhibited in the miR-20a-5p mimic group (both P<0.001). The cell proliferation abilities of NC+ empty vector group, miR-20a-5p+ empty vector group and miR-20a-5p+ KDM6B group were 0.83±0.05, 0.52±0.01 and 0.67±0.05 ( F=43.919, P<0.001), compared with the NC+ empty vector group, the cell proliferation ability was significantly inhibited in the miR-20a-5p+ empty vector group ( P<0.001); compared with the miR-20a-5p+ empty vector group, the cell proliferation ability of miR-20a-5p+ KDM6B group increased significantly ( P<0.001). The scratch healing rates of the blank control group, mimic NC group and miR-20a-5p mimic group were (32.51±2.73)%, (30.26±3.22)% and (13.52±1.77)% ( F=46.314, P<0.001), compared with the control group and the mimic NC group, the scratch healing rate of the miR-20a-5p mimic group was significantly decreased (both P<0.001). The scratch healing rates of NC+ empty vector group, miR-20a-5p+ empty vector group and miR-20a-5p+ KDM6B group were (31.34±3.11)%, (12.15±1.64)% and (28.93±2.89)% ( F=47.511, P<0.001), compared with the NC+ empty vector group, the scratch healing rate of the miR-20a-5p+ empty vector group was significantly decreased ( P<0.001); compared with the miR-20a-5p+ empty vector group, the scratch healing rate of miR-20a-5p+ KDM6B group was significantly increased ( P=0.001). The numbers of transmembrane cells in the blank control group, mimic NC group and miR-20a-5p mimic group were 114±16, 108±11 and 42±6 ( F=36.282, P<0.001), compared with the control group and mimic NC group, the number of transmembrane cells of the miR-20a-5p mimic group was significantly decreased (both P<0.001). The numbers of transmembrane cells in the NC+ empty vector group, miR-20a-5p+ empty vector group and miR-20a-5p+ KDM6B group was 143±11, 39±4 and 139±12 ( F=112.120, P<0.001), compared with the NC+ empty vector group, the number of transmembrane cells of the miR-20a-5p+ empty vector group was significantly decreased ( P<0.001); compared with the miR-20a-5p+ empty vector group, the number of transmembrane cells of the miR-20a-5p+ KDM6B group was increased significantly ( P<0.001). The tumor volumes of mice for 21 d in the NC+ empty vector group, miR-20a-5p+ empty vector group and miR-20a-5p+ KDM6B group were (1 667.50±250.40) mm 3, (129.20±21.00) mm 3 and (775.41±77.51) mm 3 respectively, with a statistically significant difference ( F=77.651, P<0.001). The tumor weights of the 3 groups were (1.35±0.18) g, (0.12±0.01) g and (0.61±0.03) g respectively, with a statistically significant difference ( F=104.191, P<0.001). Conclusion:The expression of miR-20a-5p is significantly decreased in osteosarcoma tissues, and the expression of KDM6B is significantly increased in osteosarcoma tissues. Overexpression of miR-20a-5p may inhibit the proliferation, migration and invasion of osteosarcoma cells and tumor growth by targeting to reduce the expression of KDM6B.

Objective To investigate the effect of propofol on nNOS expression after focal cerebral ischemia-reperfusion in rats and the possible mechanism of protective effect of propofol on brain. Method Seventy-eight male Wistar rats, weighting 250 ~ 300 g, were randomly divided into 3 groups:(1)Sham operation group (S group, n=6) was performed with scham operation; (2) Ischemia-reperfusion group (group I-R, n=36) was subjected to 2-hour right middle cerebral artery occlusion and then reperfusion was followed, saline (1 mg/kg) was injected into the right lateral cerebral ventricle using microsyringe before reperfusion;(3) Propefol group (group P, n=36) was injected with propofol (1mg/kg) into the right lateral cerebral ventricle using microsyringe right after ischemia. Group I-R and group P were divided into 3 subgroups according to the reperfusion time: 1 h, 3 h and 6 h. The neurological function of all rats were tested before reperfusion. The cerebral infarction area of the whole brain was calculated with TIC staining (n=6). The pathological change of brain was observed from HE staining (n=6) and the nNOS protein expression was obtained by immuno- histochemical method (n=6). Results Compared with I-R group, the neurological function was better in group P(P

OBJECTIVETo analyze the relation of plasma D-dimer levels and incidence of deep venous thrombosis after spinal surgery.

METHODSThe clinical data of 63 patients underwent spinal surgery from October 2009 to October 2010 were retrospective analyzed. There were 40 males and 23 females with an average age of 48 years old(21 to 76) in operation. Operation levels of 15 cases were in cervical vertebrae, 4 cases were in thoracic vertebrae,and 44 cases were in lumbar vertebrae. Thirty patients with spinal fracture were caused by trauma and 33 patients without trauma, 11 patients combined with nerve injury. The patients were divided into two groups according to plasma D-dimer levels, more than or equal to 500 microg/L was D-dimer positive group and less than 500 microg/L was D-dimer negative group. Venous blood of all patients early morning with empty stomach were testd on admission, and at 2 h, 1 d, 2 d, 3 d, 4 d, 6 d, 8 d, 10 d, 15 d after operation,respectively.

RESULTSThere was no statistically significant differences in sex, operative segments, implants, operative posture, age, bleed volume, body weight, peroperative D-dimer levels between two groups. After operation, plasma D-dimer of 19 patients were more than or equal to 500 microg/L, with persistent or progressive increasing. Two cases occurred deep venous thrombosis in D-dimer positive group, they respectively were found at 3 days and 8 days after operation. Both of them underwent posterior decompression and internal fixation. However,no deep venous thrombosis was found in D-dimer negative group.

CONCLUSIONPostoperative D-dimer assay can effective predict deep venous thrombosis occurrence. D-dimer level more than or equal to 500 microg/L will be considered as a risk factor for deep venous thrombosis after spinal surgery.

Adult ; Aged ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Spine ; surgery ; Ultrasonography ; Venous Thrombosis ; blood ; diagnostic imaging ; surgery ; Young Adult

AIM: To explore the frequency of drug injection of alloxan diabetes on the established model of rabbit.METHODS: Thirty-six healthy rabbits, weighing 2-2.5kg, were randomly divided into one time drug injection group (group A, n=12), two times drug injection group (group B, n=12) and three times drug injection group (group C, n=12). Each rabbit was injected with a total amount of 150mg/kg of alloxan. Fasting blood glucose was measured. The success rate and death rate of each group were also calculated.RESULTS: The success rate of diabetic rabbit model in group B was higher than that in group A (P<0.01) and its death rate was lower than that of group A (P<0.01); the success rate of diabetic rabbit model in group C was highest and the death rate was the lowest in three groups(P<0.01). CONCLUSION: Multiple administration of alloxan can improve success rate in establishing diabetic rabbit model with decreased death rate and increased stability.

AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation