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Objective@#To investigate the expression of B7H3 in neuroblastoma (NB) tissues and its relationship between clinical characteristics and prognosis of patients.@*Methods@#The clinical data and pathological wax of 100 cases with neuroblastoma admitted from January 2000 to December 2015 in Sun Yet-Sen University Cancer Center were collected.The expression of B7H3 in tumor tissues was detected by immunohistochemistry (IHC) and then the expression of B7H3 and its relation to pathological parameters and survival rate of patients were analyzed.@*Results@#(1) The positive rates of B7H3 in tumor tissues were 79% (79/100 cases), of which 37 were weak positive, 31 were mode-rate positive, 11 were strong positive, 58%(58/100 cases) showed low expression and 42%(42/100 cases) showed high expression.(2)The positive rate of B7H3 was positively correlated with the risk stratification, age, stage, primary site and N-MYC gene status (r=0.621, 0.350, 0.730, 0.224, 0.335; all P<0.05). (3)The high expression rates of B7H3 were positively correlated with the risk, stage, N-MYC gene status and tumor size (r=0.177, 0.016, 0.175, 0.284; all P<0.05). (4)B7H3 negative and positive 4-year event free survival (EFS) rates of 100 patients were 89.5% and 19.9% (χ2=31.260, P<0.001), 4-year overall survival(OS) rates were 94.7% and 48.3% (χ2=20.212, P<0.001), for 33 non-high-risk patients, B7H3 negative and positive 4-year EFS rates were 100.0% and 47.3% (χ2=8.760, P=0.003), and 4-year OS rates were 100.0% and 93.8% (χ2=1.063, P=0.003), respectively.Sixty-seven high-risk patients with B7H3 negative and positive 4-year EFS were 50.0% and 15.4% (χ2=4.093, P=0.043), 4-year OS were 75.0% and 42.0%, respectively (χ2=1.872, P=0.171). (5)The 4-year EFS rates of 100 patients with B7H3 low expression and high expression were 41.8% and 27.1% (χ2=3.801, P=0.051), and 4-year OS rates were 58.6% and 63.8% (χ2=0.111, P=0.739), respectively.The 4-year EFS and OS rates for 33 non-high-risk patients with B7H3 low expression and high expression were 94.7% and 44.2% (χ2=9.122, P=0.003), 100.0% and 90.9% (χ2=2.000, P=0.157), respectively.The 4-year EFS and OS rates of 67 high-risk patients with high expression and low expression of B7H3 were 13.9% and 22.1% (χ2=0.061, P=0.805), 36.3% and 57.7%(χ2=2.060, P=0.151), respectively.(6)Multivariate analysis showed that OS and EFS in B7H3 positive patients were lower than those in B7H3 negative patients[RR 95%CI: 28.110 (2.430-325.148); P=0.008; RR 95%CI: 12.834 (2.669-61.715), P=0.001].@*Conclusions@#The positive rate of B7H3 in neuroblastoma is high, and the expression level of B7H3 is closely related to the clinical characteristics of the patients.Positive B7H3 in tumor tissues is an independent poor prognostic factor.B7H3 may be one of the new prognostic indicators for NB.
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Objective To investigate the expression of B7H3 in neuroblastoma(NB)tissues and its relation_ship between clinical characteristics and prognosis of patients. Methods The clinical data and pathological wax of 100 cases with neuroblastoma admitted from January 2000 to December 2015 in Sun Yet_Sen University Cancer Center were collected. The expression of B7H3 in tumor tissues was detected by immunohistochemistry(IHC)and then the ex_pression of B7H3 and its relation to pathological parameters and survival rate of patients were analyzed. Results (1) The positive rates of B7H3 in tumor tissues were 79%(79/100 cases),of which 37 were weak positive,31 were mode_rate positive,11 were strong positive,58%(58/100 cases)showed low expression and 42%(42/100 cases)showed high expression.(2)The positive rate of B7H3 was positively correlated with the risk stratification,age,stage,primary site and N_MYC gene status(r=0. 621,0. 350,0. 730,0. 224,0. 335;all P<0. 05).(3)The high expression rates of B7H3 were positively correlated with the risk,stage,N_MYC gene status and tumor size( r=0. 177,0. 016,0. 175, 0. 284;all P<0. 05).(4)B7H3 negative and positive 4_year event free survival( EFS)rates of 100 patients were 89. 5% and 19. 9%(χ2 =31. 260,P<0. 001),4_year overall survival( OS)rates were 94. 7% and 48. 3%( χ2 =20. 212,P<0. 001),for 33 non_high_risk patients,B7H3 negative and positive 4 _year EFS rates were 100. 0%and 47. 3%(χ2 =8. 760,P=0. 003),and 4_year OS rates were 100. 0% and 93. 8%( χ2 =1. 063,P=0. 003),re_spectively. Sixty_seven high_risk patients with B7H3 negative and positive 4_year EFS were 50. 0% and 15. 4%(χ2 =4. 093,P=0. 043),4_year OS were 75. 0% and 42. 0%,respectively( χ2 =1. 872,P=0. 171).(5)The 4_year EFS rates of 100 patients with B7H3 low expression and high expression were 41. 8% and 27. 1%( χ2 =3. 801, P=0. 051),and 4_year OS rates were 58. 6% and 63. 8%(χ2 =0. 111,P=0. 739),respectively. The 4_year EFS and OS rates for 33 non_high_risk patients with B7H3 low expression and high expression were 94. 7% and 44. 2%(χ2 =9. 122,P=0. 003),100. 0% and 90. 9%(χ2 =2. 000,P=0. 157),respectively. The 4_year EFS and OS rates of 67 high_risk patients with high expression and low expression of B7H3 were 13. 9% and 22. 1%(χ2 =0. 061,P=0. 805),36. 3% and 57. 7%(χ2 =2. 060,P=0. 151),respectively.(6)multivariate analysis showed that OS and EFS in B7H3 positive patients were lower than those in B7H3 negative patients[RR 95%CI:28. 110(2. 430_325. 148);P=0. 008;RR 95%CI:12. 834(2. 669_61. 715),P=0. 001]. Conclusions The positive rate of B7H3 in neuroblasto_ma is high,and the expression level of B7H3 is closely related to the clinical characteristics of the patients. Positive B7H3 in tumor tissues is an independent poor prognostic factor. B7H3 may be one of the new prognostic indicators for NB.
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Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4),programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) are well studied immune checkpoint (IC) in recent years.New IC,such as lymphocyte activation gene 3 (LAG-3) and B7H3 are in progress.Several clinical trials have confirmed that inhibitors of CTLA-4 and PD-1/PD-L1 have achieved remarkable results in inhibiting tumor growth,maintaining disease stability and prolonging survival of patients.Therefore,immune checkpoint inhibitor (ICI) is expected to play a potential role in the treatment of malignant tumors in children.However,ICI also has some limitations,including uncertain efficacy and potential toxicity.It is challenging to identify the best target population,maximize the benefit of patients and minimize the risk of toxicity in future.
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·AIM: To comprehensively investigate the relationship between outer retinal layer thickness and age in normal eyes. ·METHODS: One hundred normal eyes of 100 subjects who underwent spectral - domain optical coherence tomography ( SD - OCT ) were included in this retrospective study. The distances between the external limiting membrane ( ELM ) line and the photoreceptor inner segment/outer segment ( IS/OS ) line ( ELM-IS/OS), the IS/OS line and the cone outer segment tips (COST) line ( IS/OS-COST), the COST line and the retinal pigment epithelium ( RPE) complex ( COST-RPE) and the full retinal thickness ( RT) were measured at the fovea and on four quarters. The relationship between thickness and age or sex was then analysed. ·RESULTS: A thinner RT was observed in women in a multiple regression analysis ( men: 234. 47 ± 16. 79 μ m;women: 223. 13±15. 43 μ m). The RT on the nasal quarter and the ELM-IS/OS thickness at the fovea and on the four quarters were significantly and negatively correlated with age. The IS/OS-COST and COST-RPE thicknesses at the fovea and on the four quarters were not significantly correlated with age or sex, respectively. The RT at the fovea was significantly thinner than on the four quarters. The ELM - IS/OS, IS/OS - COST and COST - RPE thicknesses at the fovea were significantly thicker than on the four quarters. ·CONCLUSION: In normal eyes, the RT thickness on the nasal quarter and the ELM - IS/OS thickness were significantly and negatively correlated with age. The IS/OS - COST and COST - RPE thicknesses were not significantly correlated with age or sex.
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[Objective]To investigate the etiology,clinical manifestation,treatment and prognosis of optic disc vas-culitis.[Method]Twenty-four eyes of 21 patients were enrolled in this retrospective study.Eye examinations,treatment, and effect were recorded.[Result]Six were male and 15 were female.The age was between 19 and 43 years old(average:28.7±1.6).85.7% of the patients referred to the clinic with mild to moderate decreased vision.Edema of the optic disc can be seen in both types while tortuous veins can also be found in type 2.Similar characteristics were noticed in OCT,FFA, and etc.With a follow-up of 4.52±0.98 months after treatment(prednisone:initial dose 1.0-1.2 mg/kg),the BCVA of the affected eyes improved significantly.[Conclusion]Optic disc vasculitis is affected by autoimmune disorder,infection,hy-perlipidemia,and etc.Edema of the optic disc with/without tortuous veins and retinal hemorrhage can be noticed.Similar diseases should be excluded in avoidance of misdiagnosis. Systemic examination and complete solution should be per-formed.Glucocorticoid helps to improve the visual function.The application of anti-VEGF is effective in secondary macu-lar edema.However,the long-term efficacy is awaiting being confirmed.
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Objective@#To investigate the relationship between expression of programmed cell death ligand-1(PD-L1) in the tissue of neuroblastoma (NB) and patient's clinical characteristics and prognosis.@*Methods@#Clinical data and surgical tissue paraffin blocks of 100 newly diagnosed NB children at Sun Yat-sen University Cancer Center between January 2000 and December 2015 were collected and the expression level of PD-L1 and its' relationship with pathological parameters and survival rate were analyzed retrospectively. The ratio between groups was compared by chi-square test. Kaplan-Meier method was used for survival analysis and COX regression model was used for multivariate analysis.@*Results@#Among 100 cases, 71 were males and 29 females; there were 5 cases of stageⅠ, 4 cases of stageⅡ, 19 cases of stage Ⅲ, 65 cases of stage Ⅳ and 7 cases of stage Ⅳs. Ten out of 62 cases (16%) were N-MYC amplified; 15 cases were in low-risk group, 18 were in medium-risk group and 67 were in high-risk group. The positive rate of PD-L1 in NB tumor tissue was 57% (57/100), of which 55 were weakly positive, 1 was moderately positive and 1 was strongly positive. The positive rates of PD-L1 expression in tumor tissues without bone metastasis were higher than those with bone metastasis(66%(39/59)vs.44%(18/41), χ2=4.864, P=0.027), the positive rates of PD-L1 expression in tumor tissues pathologically diagnosed as neuroblastoma were higher than those pathologically diagnosed as ganglioneuroblastoma (61%(53/87) vs.31%(4/13), χ2=4.195, P=0.041), the positive rates of PD-L1 expression in tumor tissues originated from abdominal cavity were higher than those originated from other places (61% (51/83)vs.35%(6/17), χ2=3.937,P=0.047).The 4-year event-free survival (EFS) rates of patients with PD-L1 negative and positive were 40% and 33% (χ2=0.009, P=0.923), respectively. The 4-year overall survival (OS) rates of patients with PD-L1 negative and positive were 62% and 58% (χ2=0.294, P=0.587). Among 33 non-high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 89% and 78% (χ2=0.001, P=0.965), the 4-year OS rates of patients with PD-L1 negative and positive were 100% and 96% (χ2=0.500, P=0.480). Among 67 high-risk patients, the 4-year EFS rates of patients with PD-L1 negative and positive were 24% and 11% (χ2=1.154, P=0.282), the 4-year OS rates of patients with PD-L1 negative and positive were 48% and 41% (χ2=0.692, P=0.405). Multivariate analysis showed that N-MYC gene amplification was an independent adverse prognostic factor for OS and EFS rates of NB patients (RR: 1.726,95%CI:1.209-2.466; RR:1.326,95%CI:1.014-1.736) and advanced clinical stage was an independent adverse prognostic factor for EFS rates of NB patients (RR: 26.498, 95%CI:3.518-199.614).@*Conclusions@#The expression of PD-L1 in NB tumor tissues was correlated with the clinical characteristics of children. However, there were no significant differences in the prognosis of patients with or without PD-L1 expression.
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Alzheimer disease (AD), the most common dementia, is a chronic, progressive and neuro-degenerative disorder. With an increasing prevalence, AD has been the third cause of death after cardio-vascular diseases and cancer in the elderly population. However, the pathogenesis of AD remains unclear, which has led to a fairly slow development of drugs for AD and a dim view of future treatments of AD. It has been a hot spot and a big challenge to develop effective, therapeutic drugs for AD. Recently, this topic was discussed via WeChat by experts from the Neuropsychiatric WeChat Group, which consists of 300 Chinese-origin neuroscientists and neuropsychiatrists in China or overseas. The experts pointed out the problems that might have misled researches on drug discovery, such as the misleading but dominating AD pathology hypotheses and problems with the platforms for drug screening. Therefore, it is important to review the pathology of AD and the treatment strategies from big data and the overall view of the disease, which may shed new light on AD therapy to develop drugs for multiple targets, leading to omni-direc-tional, comprehensive treatments of AD. The development of AD can be further classified into different stages based on the upstream factors of AD pathology. Interestingly, it has been found that the AD brain has mitochondria damage and dysfunction; long-term exposure to low doses of ionizing radiation can also cause AD-like pathological changes. These provide novel views and ideas in terms of the path-ological process and preventive and therapeutic strategies for AD.
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<p><b>OBJECTIVE</b>To research the bacteriostatic effects of Qingkailing Injection Extract (QKLIE) and combination therapy of Qingkailing Injection (QKLI) and antibiotics on bacteria carrying New Delhi metallo-3-lactamase 1 (NDM-1) blaNDM-1 resistance gene, and to determine their minimal inhibitory concentrations (MIC).</p><p><b>METHODS</b>The antimicrobial experiments of QKLIE (Radix Isatidis, baicalin, gardenia, honeysuckle) and combination therapy of QKLI and antibiotics were performed by using the agar dilution method and K-B method. The MIC was determined from each extract.</p><p><b>RESULTS</b>There were different degrees of inhibitory effects on resistant bacteria carrying blaNDM-1 by extracts from main components of QKLI. Of them, the inhibitory effect of baicalin was the best and the MIC of the resistant bacteria was 0.015 g/mL to WD, 0.020 g/mL to WX, 0. 005 g/mL to WJ, and more than 0.020 g/mL to pGEX-4T-NDM-1/DH5alpha (GST-NDM-1), respectively. The MIC value of each extract was sequenced from high to low as baicalin, honeysuckle, gardenia, and Radix Isatidis. Furthermore, combination therapy of QKLI and antibiotics greatly enhanced the antimicrobial activity of each antibiotics when used alone, showing very obvious antibacterial effects on multidrug resistant bacteria carrying blaNDM-1 gene. Of them, the optimal effects were obtained when combined with penicillins (penicillin G, mezlocillin, piperacillin/ tazobactam, ampicillin/sulbactam), with the antibacterial effects improved by 10 folds. The antibacterial effects of other kinds of antibiotics were improved to some extent. Conclusions QKLIE and combination therapy of QKLI and antibiotics showed better bacteriostatic effects on resistant bacteria carrying blaNDM-1 gene. This study provided theoretical bases for drug development, medication and treatment for super-resistant bacteria carrying blaNDM-1.</p>
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Antibacterianos , Farmacologia , Bactérias , Genética , Farmacorresistência Bacteriana Múltipla , Genética , Quimioterapia Combinada , Medicamentos de Ervas Chinesas , Farmacologia , beta-Lactamases , GenéticaRESUMO
<p><b>UNLABELLED</b>This study is conducted to explore an effective culture method for supporting the embryo development. The cattle fetal ear fibroblasts and the goat fetal ear fibroblasts are transplanted into the enucleated cattle oocytes separately by oocyte intraplasmic nuclear injection method to construct bovine cloned embryos and goat-bovine cloned embryos. The embryos are first cultivated in modified charles rosenkrans 2 amino acid medium (mCR2aa) and modified synthetic oviduct fluid medium (mSOF) separately. Then BSA (8 mg/mL) or FBS (10%) can be added to mSOF according to the different culture period. The supplements and orders, added during the first three days and after three days are as follow: BSA and BSA, BSA and FBS, FBS and BSA, FBS and FBS. On the basis of the cleavage rate, 8/16-cell rate, blastocysts rate and total cell number of blastocysts, the best culture way can be screened out.</p><p><b>RESULT</b>First, cleavage rate, 8/16-cell rate, blastocysts rate and total cell number of blastocysts, cultivated in mSOF solution are all higher than those cultivated in mCR2aa( P < 0.05). Second, the cleavage rate and 8/16-cell rate, adding BSA and FBS into mSOF, are in turn 79.8% +/- 7.1%, 49.7% +/- 3.5%, 21.5% +/- 1.8%, and 115.2 +/- 4.3 in bovine cloned embryo, and 40.1% +/- 6.3%, 29.2% +/- 2.0%, 13.4% +/- 2.1% and 100.1 +/- 3.0 in goat-bovine cloned embryo, which are significant higher than other culture groups (P < 0.05).</p><p><b>CONCLUSION</b>The goat-bovine cloned embryo can be cultivated by the optimized culture measure of bovine cloned embryo. The best culture ways of bovine cloned embryo and goat-bovine cloned embryo are all to use mSOF supplemented BSA in the first three days and then use mSOF supplemented FBS in the next five days.</p>