Background Research demonstrated that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluR2 (AMPA-GluR2) is associated with amblyopia.It has been shown that levodopa and cytidine diphosphate choline can improve visual function of amblyopic children,but the mechanism is unclear.Objective This study was to explore the possible effects of levodopa and cytidine diphosphate choline on amblyopia.Methods Monocular deprivation (MD) animal models were created in 60 2-week-old SD rats by monolateral eyelid suturing and observed for 31 days and reared in natural light together with 15 other matched normal healthy SD rats.The models were randomly divided into the MD group,levodopa group,cytidine diphosphate choline group and normal saline control group,with 15 rats for each group.40 mg/kg of levodopa,80 mg/kg of cytidine diphosphate choline,I ml normal saline were given to the rats,respectively,for 28 consecutive days.Expressions of the AMPA-CluR2 protein and AMPA-CluR2 mRNA in the rat visual cortex were detected by immunohistochemistry,Western blot and real-time fluorescence quantitative PCR.Use of the animals followed the Regulations for the Administration of Affairs Concerning Experimental Animals by State Science and Technology Commission.Results The expression values of the AMPA-GluR2 protein (AMPA-GluR2/β-actin) and AMPA-GluR2 mRNA (2-△△Ct) were significantly lower in the MD group than those of the normal control group (protein:0.32 ± 0.02 vs.0.64 ± 0.05,t =13.287,P＜0.05 ;mRNA:0.30±0.01 vs.0.84±0.03,t=38.184,P＜0.05).Those in the levodopa group were significantly increased in comparison with the normal saline solution group (protein:0.59 ±0.04 vs.0.33 ±0.03,t =11.628,P＜0.05 ; mRNA:0.71±0.06 vs.0.33 ±0.02,t =13.435,P＜0.05).The expression values of the AMPA-GluR2 protein and AMPA-GluR2 mRNA were significantly increased in the cytidine diphosphate choline group compared with the normal saline solution group (protein:0.52 ± 0.04 vs.0.33 ± 0.03,t =8.497,P ＜ 0.05 ; mRNA:0.48± 0.04 vs.0.33 ± 0.02,t =7.500,P＜0.05).Conclusions AMPA-GluR2 is associated with the plasticity of visual development.Levodopa and cytidine diphosphate choline may improve visual function by down-regulating the expression of AMPA-GluR2 in the visual cortex.

Carcinoma, Renal Cell ; Humans ; Kidney Neoplasms ; Nomograms ; Prognosis ; Progression-Free Survival ; Retrospective Studies

BACKGROUNDRhabdomyosarcoma (RMS) is an uncommon malignancy of the breast. The aim of this study was to summarize its clinicopathologic features and biological behavior.

METHODSFive primary or secondary breast RMSs were collected. Their clinicopathological characteristics and all published literature about breast RMS were reviewed. Immunohistochemical study of desmin, myogenic differentiation 1 (MyoD1), myogenin, leukocyte common antigen (LCA), vimentin, cytokeratin (AE1/AE3), E-cadherin, neuron specific enolase (NSE), CD99, chorioallantoic membrane 5.2 (CAM5.2) and epithelial membrane antigen (EMA) expression were performed.

RESULTSThe five patients were all female with ages ranging from 16 to 46 years old (mean, 30 years). Three were metastatic breast RMSs, two embryonal and one solid variant alveolar, with the primary tumor sites the right labium majus, left nasal meatus and nasopharynx, respectively. The other two, one embryonal and one alveolar, were primaries. Grossly, the surgical specimens revealed round or oval, well-demarcated but nonencapsulated masses. Their cut surfaces consisted of homogeneous grayish yellow or white tissue. Microscopically, most tumor cells were poorly differentiated small round, oval or small polygons with eosinophilic cytoplasm. All cases were positive for vimentin, desmin, MyoD1 and myogenin. One embryonal RMS also had a few cells with perinuclear staining of AE1/AE3. The other markers were negative.

CONCLUSIONSAlthough primary or metastatic RMS in breast was almost confined to young adolescent females, our cases suggested that it can also happen to the middle-aged women. Embryonal RMS has a certain metastatic potential. MyoD1 and myogenin are two useful markers when making differential diagnosis. Axillary lymph node status and age may play a role in the prognosis of primary breast RMS patients.

Adolescent ; Adult ; Breast Neoplasms ; diagnosis ; metabolism ; Female ; Humans ; Immunohistochemistry ; Middle Aged ; Rhabdomyosarcoma ; diagnosis ; metabolism ; Young Adult

OBJECTIVETo investigate the clinical features and surgical strategy for pediatric intractable epilepsy due to posterior quadrantic cortical dysplasia and to assess the surgical outcomes.

METHODSThe clinical features and preoperative evaluation results of 14 children with intractable epilepsy due to posterior quadrantic cortical dysplasia were retrospectively analyzed. The localization values of video-electroencephalography and intraoperative monitoring and the indications, advantages and disadvantages of temporoparietooccipital disconnection were evaluated.

RESULTSThe 14 children had different seizure types, of which spasm was the most common one. The lesions of cortical dysplasia involved the central cerebral region in 2 cases. After temporoparietooccipital disconnection in 14 patients, 13 cases were seizure-free; only one case still had seizures, but the frequency dropped by more than 50%.

CONCLUSIONSTemporoparietooccipital disconnection is a safe and effective surgical procedure for children with intractable epilepsy due to posterior quadrantic cortical dysplasia.

Child ; Child, Preschool ; Electroencephalography ; Epilepsy ; etiology ; physiopathology ; surgery ; Evoked Potentials, Somatosensory ; Female ; Humans ; Infant ; Male ; Malformations of Cortical Development ; complications

The study was aimed to investigate the effect of deriving hematopoietic cells from human embryonic stem cells (hESCs) by the erythropoietin gene-modified conditioned medium of human mesenchymal cells. The mesenchymal stem cells (MSCs) steadily expressing EPO were established by lentiviral system. The expression of exogenous EPO was detected by RT-PCR and Western blot. After suspension culture, hESCs developed into embryonic bodies (EBs). Then the EB cells were cultured in conditional medium. The hESCs-derived hematopoietic cells were analyzed by immunofluorescence, CFU assay and RT-PCR. The results indicated that the exogenous EPO successfully expressed in the EPO transfected MSCs (EPO/MSCs). The supernatant from EPO/MSCs increased CD34(+) cell population and the expression of globin, and enhanced colony forming unit incidence. These effects were obviously higher than that of control. It is concluded that the EPO gene-modified conditioned medium of human mesenchymal cells can induce the hESCs to differentiate into hematopoietic cells.
Cell Culture Techniques ; Cell Differentiation ; drug effects ; Culture Media, Conditioned ; pharmacology ; Embryonic Stem Cells ; cytology ; drug effects ; Erythropoietin ; genetics ; pharmacology ; Hematopoietic System ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Organisms, Genetically Modified

Background: Approximately 15–20% cases of systemic lupus erythematosus (SLE) are diagnosed in children. There have been a few studies reporting the epidemiological data of pediatric?onset SLE (cSLE) in China, neither comparing the differences between cSLE and adult?onset SLE (aSLE). The aim of this study was to describe the impact of age of onset on clinical features and survival in cSLE patients in China based on the Chinese SLE Treatment and Research group (CSTAR) database. Methods: We made a prospective study of 225 cSLE patients (aged <16 years) and 1759 patients aged 16–50 years based on CSTAR registry. We analyzed initial symptoms, clinical presentations, SLE disease activity, damages, and outcomes of cSLE, as well as compared with aSLE patients. Results: The mean age of cSLE patients was 12.16 ± 2.92 years, with 187 (83.1%) females. Fever (P < 0.001) as well as mucocutaneous (P < 0.001) and renal (P = 0.006) disorders were found to be significantly more frequent in cSLE patients as initial symptoms, while muscle and joint lesions were significantly less common compared to aSLE subjects (P < 0.001). The cSLE patients were found to present more frequently with malar rash (P = 0.001; odds ratio [OR], 0.624; 95% confidence interval [CI ], 0.470–0.829) but less frequently with arthritis (P < 0.001; OR, 2.013; 95% CI, 1.512–2.679) and serositis (P = 0.030; OR, 1.629; 95% CI, 1.053–2.520). There was no significant difference in SLE disease activity index scores between cSLE and aSLE groups (P = 0.478). Cox regression indicated that childhood onset was the risk factor for organ damage in lupus patients (hazard ratio 0.335 [0.170–0.658], P = 0.001). The survival curves between the cSLE and aSLE groups had no significant difference as determined by the log?rank test (0.557, P = 0.455). Conclusions: cSLE in China has different clinical features and more inflammation than aSLE patients. Damage may be less in children and there is no difference in 5? year survival between cSLE and aSLE groups.

BACKGROUNDGenetic susceptibility is one of the major etiological factors for nasopharyngeal carcinoma (NPC). Among the genetic predisposing factors, human leukocyte antigen (HLA) genes have been reported to be associated with NPC. This study aimed to investigate the associations of HLA-DRB1 alleles with NPC and the clinical significance of HLA-DRB1 alleles in NPC.

METHODSFrom January 2009 to December 2013, 140 NPC patients (118 Han patients and 22 Uyghur patients) and 158 healthy controls (81 Han individuals and 77 Uyghur individuals) from Xinjiang Province were genotyped for HLA-DRB1 using the polymerase chain reaction-sequence specific primer technique. Chi-square analysis was used when comparing allele frequencies between groups. The clinical outcomes were evaluated by Kaplan-Meier method and Cox regression model.

RESULTSCompared with healthy controls, the allele frequency of HLA-DRB1*0701 was increased in the Uyghur patients (P = 0.008) but not in the Han patients (P = 0.869). HLA-DRB1*0101 allele was presented with higher frequency in clinical Stage I + II group compared with clinical Stage III + IV group in the Han patients (P = 0.015) but not in the Uyghur patients (P = 1.000). Higher frequency of HLA-DRB1*1501 allele was observed in patients aged <45 years compared with those in patients aged ≥45 years (P = 0.002). Neither HLA-DRB1*0701 nor HLA-DRB1*0101 had a statistically significant association with 3-year survival.

CONCLUSIONSThis study found HLA-DRB1*0701 in Uyghur population was associated with an increased risk of developing NPC. In Han population, we found HLA-DRB1*0101 was associated with protection from disease progression, and HLA-DRB1*1501 was associated with early age of onset. HLA-DRB1 could not be identified as a prognostic indicator for NPC in either Han or Uyghur patients.

Adult ; Asian Continental Ancestry Group ; Carcinoma ; China ; Female ; Gene Frequency ; genetics ; Genetic Predisposition to Disease ; genetics ; Genotype ; HLA-DRB1 Chains ; genetics ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Polymorphism, Genetic ; genetics ; Prognosis

OBJECTIVE: To explore the prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma for the risk stratification of such patients. METHODS: Clinical data of patients with locally advanced renal cell carcinoma in the Third Hospital of Peking University from January 2015 to December 2017 were collected. The patients were divided into progression group and progression-free group according to follow-up data, and preoperative platelet parameters and clinical data between the two groups were compared. The optimal cut-off value of platelet parameters was determined by receiver operating characteristic curve (ROC) and analyzed by Kaplan-Meier survival curve. Cox proportional hazards model was used to analyze the independent risk factors of PFS. Time dependent ROC curve, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the improvement of SSIGN model by incorporating platelet parameters. RESULTS: Of the 215 patients, 192 (89.3%) were followed up for a median of 36 months. Sixty-four patients (29.8%) had disease progression during the follow-up, and the median PFS was 46 months. In progression group, the platelet count (PLT) was higher [(250.72 ± 88.59)×10⁹/L vs. (227.27 ± 66.94)×10⁹/L, P=0.042] and the platelet distribution width (PDW) was lower [(12.01 ± 2.27)% vs. (13.31 ± 2.74)%, P = 0.001] than that of progression-free groups. 285×10⁹ /L and 12.65% as the best cut-off values of PLT and PDW, the median PFS of PLT≤285×10⁹ /L group was significantly longer than that of PLT>285×10⁹ /L group (53 months vs. 41 months, P=0.033), and the median PFS of PDW>12.65% group was also significantly longer than that of PDW≤12.65% group (56 months vs. 41 months, P < 0.001). Multivariate analysis showed that preoperative PDW (HR=0.735, P < 0.001), nuclear grade Ⅲ to Ⅳ (HR=2.425, P=0.001) and sarcomatoid differentiation (HR=3.101, P=0.008) were independent risk factors for PFS. The area under the curve of PDW combined with SSIGN model was larger than that with the original SSIGN model [0.748 (95%CI: 0.662－0.833) vs. 0.678 (95%CI: 0.583－0.773), P=0.193], NRI was 0.262 (P=0.04), and IDI was 0.085 (P=0.01), indicating that the predictive ability of PDW combined with SSIGN model was improved. CONCLUSION Preoperative high PLT and low PDW are associated with adverse prognosis of locally advanced renal cell carcinoma, and PDW is an independent risk factor. Therefore, preoperative PDW could serve as biomarker for risk stratification of locally advanced renal cell carcinoma.
Carcinoma, Renal Cell/surgery* ; Humans ; Kidney Neoplasms/surgery* ; Platelet Count ; Prognosis ; ROC Curve ; Retrospective Studies

OBJECTIVE To establish the mice model of chronic obstructive pulmonary disease (COPD) complicated with depression induced by smoke,and to evaluate the therapeutic effects and mechanism of modified Wendan Decoction on these mice models.METHODS Mice were randomly divided into normal control group and model group.Model group was given smoke four times a day.After 15 weeks,sugar consumption of both the model group and the control group were tested as well as the pathological changes of airway and lung tissue of the two groups were observed.In recognition of COPD with depression models being successfully constructed,mice in the model group were further randomly divided into model group,high dose group of Modified Wendan Decoction,low dose group of Modified Wendan Decoction and positive drug group,with the medi-cine administration lasting for 3 weeks.Then the sugar consumption,tail suspension test,pulmonary function and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of each group were tested and the airway and lung tissue patho-logical changes were once more observed.RESULTS Compared with normal control group,the weight and sugar consumption of model group decreased and the enhanced respiratory pause(Penh)increased after 15 weeks of smoking.Compared with the model group,the body weight and sugar consumption of the Modified Wendan Decoction group increased,with significantly re-duced inspiratory resistance(RI),increased lung dynamic compliance(Cdyn),decreased total number of leukocyte and neutro-phils than those of the model group.In addition,the bronchoalveolar lavage fluid and inflammatory factors in hippocampus were decreased.CONCLUSION The COPD with depression mouse model established by smoke is in accordance with the dis-ease development and and its clinical features.Chinese medicine Modified Wendan Decoction has therapeutic effects on the im-provement of pathological and functional changes in mice with COPD and depression.

BACKGROUNDChronic stress contributes to increased risks of atherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis (AS).

METHODSFifty male New Zealand white rabbits were used. Aortic balloon-injury model was applied. Both social stress and physical stress methods were adopted to establish chronic stress models. The lumen stenotic degree, intimal and medial areas, maximum fibrous cap thickness, and plaque contents were measured with histological sections. Proteomic methods were applied to detect protein changes in abdominal aortas to identify the specialized mediators. Real-time reverse transcription-polymerase chain reaction was used for further verification and investigation.

RESULTSThe stress rabbits exhibited lower body weight, worse fur state, more inactivity behavior, and higher serum cortisol level. Chronic stress was significantly associated with the decreased medial area and increased plaque instability, which was manifested by thinner fibrous caps, larger lipid cores, more macrophages, and new vessels but fewer smooth muscle cells and elastic fibers. After chronic stress, the apoptosis-related genes UBE2K, BAX, FAS, Caspase 3, Caspase 9, and P53 were upregulated, and BCL-2/BAX was down-regulated; the angiogenesis-related genes ANG and VEGF-A were also highly expressed in atherosclerotic arteries.

CONCLUSIONSRabbit models of chronic stress were successfully established by applying both social stress and physical stress for 8 weeks. Chronic stress can reduce AS tunica media and accelerate plaque instability by promoting apoptosis and neovascularization.