中国肝病患者血清铜蓝蛋白水平的研究

目的　探讨我国不同肝病患者血清铜蓝蛋白 (CP)水平交叉程度 ,为肝豆状核变性(WD)的诊断和鉴别诊断提供科学的依据。方法　测定 90 5例正常人、WD及其他各种肝病患者血清CP水平 ,采用SPSS12统计软件进行统计分析。结果　WD患者血清CP平均为 (93 9± 98 1)mg/L ,与其他各组相比差异有非常显著性 ,72 7%的患者低于 10 0mg/L ,其中 4 2 9%的患者低于 5 0mg/L ,但是也有 9 1%的患者其血清CP正常 ,其中 3例高于 4 0 0mg/L ,最高达 5 0 1mg/L。 6 8%的非WD患者血清CP低于正常 ,最低为 2 8mg/L。急性肝炎患者血清CP平均为 (398 4± 15 1 3)mg/L ,显著高于其他各组。重型肝炎患者血清CP平均为 (2 96 5± 10 6 5 )mg/L ,显著低于其他各组 ,其中18 8%的患者低于正常。结论　WD患者CP水平显著低于正常人和其他肝病患者 ,但是与其他肝病有一定程度的交叉 ,单凭CP水平不足以确诊或排除WD。     

Expression of p21(WAF1) and p53 and polymorphism of p21(WAF1) gene in gastric carcinoma

AIM: To investigate the relationship between expression of p21(WAF1) and p53 gene, and to evaluate the deletion and polymorphism of p21(WAF1) gene in gastric carcinoma (GC). METHODS: Expression of p21 and p53 proteins, and deletion and polymorphism of p21 gene in GC were examined by streptavidin-peroxidase conjugated method (SP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. RESULTS: The expression of p21 and p53 was found in 100% (20/20) and 0% (0/20) of normal gastric mucosae(NGM), 92.5% (37/40) and 15.0% (6/40) of dysplasia (DP) and 39.8% (43/108) and 56.5% (61/108) of GC, respectively. The positive rate of p21 in GC was lower than that in NGM and DP (P<0.05), while the positive rate of p53 in GC was higher than that in NGM and DP (P<0.05). p21 and p53 were significantly expressed in 63.3% (19/30) and 36.7% (11/30), 35.0% (14/40) and 77.5% (31/40), 26.7% (4/15) and 80.0% (12/15), 30.8% (4/13) and 30.8% (4/13), and 20.0% (2/10) and 30.0% (3/10) of well-differentiated, poorly-differentiated, undifferentiated carcinomas, mucoid carcinomas and signet ring cell carcinomas. The expression of p21 in well-differentiated carcinomas was significantly higher than that in poorly-differentiated, un-differentiated, mucoid carcinomas and signet ring cell carcinomas (P<0.05). Contrarily, The expression of p53 was increased from well-differentiated to poorly-differentiated and un-differentiated carcinomas (P<0.05). The expression of p21 and p53 in paired primary and metastatic GC (35.3% and 70.6%) was different from non-metastatic GC (62.5% and 42.5%) markedly (P<0.05). The expression of p21 in invasive superficial muscle (60.0%) was higher than that in invasive deep muscle or total layer (35.2%) (P<0.05) and was higher in TNM stages I (60.0%) and II (56.2%) than in stages III (27.9%) and IV (22.2%) (P<0.05), whereas the expression of p53 did not correlate to invasion depth or TNM staging (P>0.05). The exoression patterns of p53+/p21-, and of p53-/p21+ were found in 5.0% and 82.5% of DP. There was a significant correlation between expression of p21 and p53 (P<0.05). But there was no significant correlation between expression of both in GC (P>0.05). There was no deletion in exon 2 of p21 gene in 30 cases of GC and 45 cases of non-GC, but polymorphism of p21 gene at exon 2 was found in 26.7% (8/30) of GC and 8.9% (4/45) of non-GC, a significant difference was found between GC and non-GC (P<0.05). There was no significant relation between p21 expression of polymorphism (37.5%, 3/8) and non-polymorphism (45.5%, 10/22) in GC (P>0.05). CONCLUSION: The loss of p21 protein and abnormal expression of p53 are related to carcinogenesis, differentiation and metastasis of GC. The expression of p21 is related to invasion and clinical staging in GC intimately. The expression of p21 protein depends on p53 protein largely in NGM and DP, but not in GC. No deletion of p21 gene in exon 2 can be found in GC. The polymorphism of p21 gene might be involved in gastric carcinogenesis.There is no significant association between polymorphism of p21 gene and expression of p21 protein.     

18F-FDG PET/CT features of ureteral metastases from breast cancer: a case report

Breast cancer metastasis to the ureter is rare. Fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) is widely used to identify primary lesions of metastatic tumours, however, 18F-FDG PET/CT imaging features of ureteral metastasis from breast cancer are rarely reported. Herein, the case of a 46-year-old woman with recurrent left flank pain for 5 months, who was admitted to the Cancer Hospital of Guangxi Medical University and Guangxi Cancer Research Institute, is described. She had undergone right radical mastectomy 5 years previously and had received tamoxifen treatment for 5 years. Assessment by 18F-FDG PET/CT revealed tumours on the ureter presenting as a long segmental lesion, radioactive concentrations, and a low maximum standardized uptake value (SUVmax), with no radioactive concentrations in the urine and no significant change in the ureteral contour. The severity of the ureteral lesion was not consistent with the severity of hydronephrosis. A tumour biopsy was performed laparoscopically, and postoperative pathological examination confirmed a primary breast cancer tumour. The patient did not consent to treatment and was lost to follow-up.     

Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.     

Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia reperfusion injury

Nanoparticles (NPs) with modification of brain-targeting molecules have been extensively exploited for therapeutic gene delivery across the blood–brain barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy. Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important target for gene therapy against cerebral ischemia reperfusion injury. In this study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a μ-opiate receptor agonist) through PEG for efficient brain-targeting, then complexed with anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL-PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting ability. In vitro, increased cellular uptake and transfection efficiency were explored; in vivo, preferable accumulation and gene transfection in brain were showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell death was apparently decreased and cerebral infarct area was significantly reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and safe for brain-targeting RNAi neuroprotection against cerebral ischemia reperfusion injury.     

Anti-CCL25 Antibody Prolongs Skin Allograft Survival by Blocking CCR9 Expression and Impairing Splenic T-Cell Function

Chemokines, by virtue of their ability to recruit immune cells into allografts, play critical roles in acute transplantation rejection. CCR9 and its ligand, CCL25, is one of the key regulators of thymocyte migration and maturation in normal and inflammatory conditions. Moreover, several studies have revealed that high expression of CCR9 and CCL25 participated in many kinds of diseases. However, the role of CCR9 in allograft rejection is still unclear. In this study, we established a murine skin transplantation model of acute rejection. Our findings showed that the proportion of CCR9-expressing T cells was significantly increased in the spleen of allotransplanted mice compared with syngeneic transplantation. Furthermore, expression of CCL25 in allograft was similarly increased. Neutralization of CCL25 by intravenous injection of anti-CCL25 monoclonal antibody significantly prolonged skin allograft survival, decreased the number of infiltrating cells, and simultaneously suppressed the chemotactic ability and the proliferation of the splenic T cells in response to allogeneic antigens. Finally, blockade of CCL25 also diminished the secretion of IFN-γ by splenic T cells. These studies indicated that CCR9/CCL25 was involved in acute transplantation rejection and anti-CCL25 strategies might be useful in preventing acute rejection.     

Technical note: multi-alleles at the DYS385ab locus with high frequency in a Han Chinese population from southwestern China

International Journal of Legal Medicine - Y-chromosome short tandem repeat (Y-STR) markers have been widely used in forensic applications and usually show monoallelic or diallelic genotypic...     

Disrupted Intersubject Variability Architecture in Functional Connectomes in Schizophrenia

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.