ABSTRACT
Reform of public hospitals is key to the healthcare system reform.This article introduced how Hangzhou implemented such a reform of " Hangzhou characteristics" by referring to the hospital reform framework of the World Bank, and the theoretical achievements and practical experiences of domestic public hospitals′reform.Led by the service concept of " Medicine has its limitations but we have the courage to overcome, service is boundaryless and we must pursue excellence" , Hangzhou has established a public hospital value system of " reorientation to public welfare".The smart healthcare system serves as a focus, to support the delicacy management of the hospitals. The construction of hierarchical medical care system functions as the pillar, to support the coordinated development of hospitals, primary health institutions and public health institutions.This way a public hospital comprehensive reform mode is established featuring " one value system, 2 levels of organization structure, 6 mechanisms, and 19 supporting measures ". Its experiences may serve as reference to streamline hospital internal operation and external cooperation mechanism.
ABSTRACT
PURPOSE: The characteristic expression of DNA damage response proteins in familial breast cancers with BRCA1, BRCA2, or non-BRCA1/2 mutations has not been analyzed in Chinese patients. Our study aimed to assess the differential expression of microcephalin 1 (BRIT1), ATM serine/threonine kinase (ATM), checkpoint kinase 2 (CHEK2), BRCA1, RAD51 recombinase (RAD51), and poly (ADP-ribose) polymerase 1 (PARP-1) and establish the profile of Chinese familial breast cancers with different mutation status. METHODS: We constructed five tissue microarrays from 183 familial breast cancer patients (31 with BRCA1 mutations; 14 with BRCA2 mutations, and 138 with non-BRCA1/2 mutations). The DNA response and repair markers used for immunohistochemistry analysis included BRIT1, ATM, CHEK2, BRCA1, RAD51, and PARP-1. The expressions of these proteins were analyzed in BRCA1/2 mutated tumors. The association between pathologic characteristics with BRCA1/2 mutation status was also analyzed. RESULTS: In familial breast cancer patients, BRCA1 mutated tumors were more frequent with high nuclear grade, estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, low Ki-67, and positive CK5/6. BRCA1 mutated tumors had lower CHEK2 and higher cytoplasmic BRIT1 expression than BRCA2 and non-BRCA1/2 mutation tumors. BRCA2-associated tumors showed higher CHEK2 and cytoplasmic RAD51 expression than those in other groups. Nuclear PARP-1 expression in BRCA1/2-associated tumors was significantly higher than in non-BRCA1/2 mutation tumors. Moreover, we found quite a few of negative PARP-1 expression cases in BRCA1/2 mutated groups. CONCLUSION: The clinicopathologic findings of BRCA1-associated Chinese familial breast cancers were similar to the results of other studies. Chinese familial breast cancer patients with BRCA1/2 mutations might have distinctive expression of different DNA damage response proteins. The reduced expression of PARP-1 in Chinese BRCA1/2 mutated breast cancer patients could influence the therapeutic outcome of PARP-1 inhibitors.
Subject(s)
Humans , Asian People , Breast Neoplasms , Breast , Checkpoint Kinase 2 , Cytoplasm , DNA Damage , DNA Repair , DNA , Estrogens , Genes, BRCA1 , Genes, BRCA2 , Immunohistochemistry , Phosphotransferases , Rad51 Recombinase , ErbB ReceptorsABSTRACT
Objective@#To investigate the expression and significance of ubiquitin-specific proteases 2-69(USP2-69) in invasive ductal carcinoma of breast.@*Methods@#Twenty-four cases of human breast tissue with invasive ductal carcinoma diagnosed at Huanshan Hospital, Fudan University from 2013 to 2015 were collected, and the expression of USP2-69 mRNA and protein was detected by molecular hybridization, Western blot and immunohistochemistry. USP2-69 was over-expressed in cultured human breast cancer cell line MCF-7 by USP2-69 plasmid transfection. The cellular proliferative activity was investigated in vitro.@*Results@#The USP2-69 mRNA and protein were highly expressed in breast invasive ductal carcinoma, compared to adjacent normal tissues (P<0.01). Ki-67 protein expression was also increased in cases with high USP2-69 protein level. Western blot showed significantly higher USP2-69 protein level in cancer tissue compared to the adjacent normal tissue. In the cultured tumor cells, there was increased S phase fraction, cellular proliferation rate, flat positive clones, cyclin D1 expression and decreased p27 expression in USP2-69-transfected MCF-7 cells.@*Conclusions@#USP2-69 is over-expressed in breast invasive ductal carcinoma, and is closely related to proliferation promoting effects. The data provide an important experimental basis for further study on the molecular mechanism of breast cancer cell proliferation.
ABSTRACT
Objective@#To investigate the effect of triptolide on human oral cancer cell (HB) proliferation and phosphates and tensin homologue deleted on chromosome ten gene (PTEN) mRNA expression in oral cancer.@*Methods@#The cancer cells were cultured in the medium containing triptolide of different concentrations for 24, 48 and 72 h. Methyl thiazolyl tetrazolium (MTT) method was used to test the rate of growth inhibition of cancer cells, flow cytometer to detect the change of cell cycle and reveres transcription-PCR (RT-PCR) to examine the expression of PTEN mRNA. The expression of PTEN protein was examined by Western blotting.@*Results@#The rate of growth inhibition was (26.92 ± 0.14)%, (38.67 ± 0.11)%, (72.62 ± 0.89)% and (90.42 ± 0.28)%, respectively. The corresponding expression of PTEN mRNA was (3.59±0.21)%, (5.27±0.40)%, (7.18±0.44)% and (9.16±0.50)%, respectively and the corresponding A value of PTEN protein was 0.135±0.007, 0.410±0.020, 0.447±0.017 and 0.884±0.066, respectively. The proportion of G1 phase cells increased from (58.78±0.98)% to (84.13±0.47)%, but the proportion of S phase cells decreased from (25.40±0.43)% to (9.41±0.73)%.@*Conclusions@#The triptolide not only had inhibitory effect on the HB proliferation, but also affected the cell cycle.
ABSTRACT
Objective To investigate the regulatory effect of adrenomedullin (AM) on the cell-cell contact formation of podocytes and the possible mechanism.Methods Podocytes were treated with AM (10-7 mol/L),AM combined with a PKA inhibitor H89 (10-4 mol/L),and forskolin (10-5 mol/L) as positive control respectively for 12 hours.Immunofluorescent staining was applied to observe the distribution of cell adhesion molecules and actin-associated proteins.Western blotting assay was used to assess their protein levels.Rho GTPases activity was analyzed by GST-pull down assay and their protein levels were tested by Western blotting.Results AM induced the redistribution of adhesion molecules,actin-associated proteins as well as the F-actin at cell-cell contacts between podocytes.This effect was similar to that of forskolin and could be blocked by H89.The levels of those proteins did not change significantly (P ＞ 0.05).AM up-regulated the activities of RhoA,Rac1 and Cdc42 (P ＜ 0.05),which were partially blocked by H89.The protein levels of Rho GTPases showed no difference compared with the control (P ＞ 0.05).Conclusions AM may promote cell-cell contact formation of podocytes,probably through enhancing the activity of Rho GTPases and then resulting in the redistribution of adhesion molecules,actin-associated proteins and F-actin,which is partially mediated through cAMP-PKA signaling pathway.
ABSTRACT
@#Alcoholic dementia is increasingly becoming both a severe medical issue and a social problem; the unknown overall mechanism is the bottleneck for effective intervention and treatment of alcoholic brain injury. As the primary structure for the release, transmission of neurotransmitter and information integration between neurons, synapse plays a significant role in performing the advanced function of brain, such as learning and memory. Based on the neurobiological principles of synaptic structure and function, the changes in process and efficiency of synaptic transmission and information integration stressed by alcoholic molecular were reviewed in comparison with the normal process. The molecular mechanisms for alcoholic brain damage in learning and memory abilities were systematically discussed from the levels of synaptic morphology, material components, and signal transduction, respectively, and the repairing strategies for the damaged synaptic structure were proposed accordingly. Hopefully, this review could provide a deep insight into understanding the molecular mechanism of alcoholic brain damage, and draw ideas for the memory-enhancing peptides development.
ABSTRACT
Object: To investigate the effects of Huaiqihuang Granule, a compound Chinese herbal medicine, on expressions of nephrin and podocin of slit diaphragm of glomerular podocytes in rats with adriamycin-induced nephrosis and to explore the mechanism in reducing the proteinuria. Methods: Twenty SD rats were randomly divided into five groups: control group, model group, glucocorticoid group, Huaiqihuang Granule group and Huaiqihuang Granule plus glucocorticoid group. The 24-hour urine was collected 7, 14, 21 and 28 days after adriamycin injection respectively to measure 24-hour urinary protein, and all rats were sacrificed after 28-day treatment. Pathological changes in renal tissues were observed under a light microscope and an electron microscope. Expressions of nephrin and podocin mRNAs in renal cortex were determined by real-time polymerase chain reaction, and protein levels of nephrin and podocin were detected by Western blotting. Results: (1) In the model group and the treatment groups, the level of urinary protein increased significantly from the 14th day. (2) Under the light microscope, inflammatory cells and slight fibroplasia were found in renal interstitium of the model group, but there were less inflammatory cells in renal interstitium in the intervention groups than in the model group. Under the electron microscope, 29 days after adriamycin injection, extensive fusion of foot processes was observed. (3) The expressions of nephrin and podocin were higher in treatment groups than in the model group. (4) Proteinuria level was negatively correlated with the expressions of nephrin mRNA and nephrin and podocin proteins. Conclusion: The above results indicate that Huaiqihuang Granule can maintain the integrity of the slid diaphragram in podocyte, alleviate the lesion of glomerular filtration membrane, and decrease the proteinuria by up-regulating the expressions of nephrin and podocin. Huaiqihuang Granule plus glucocorticoid maybe has better effects than glucocorticoid alone.
ABSTRACT
Objective To examine the expression of response gene to complement 32 (RGC-32) in renal tissue of children with IgA nephropathy (IgAN), and to explore its significance. Methods The subjects were 45 children diagnosed as IgAN by renal biopsy. The expression of RGC-32, α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGF-β1) was examined by immunohistochemistry staining. The correlation of RGC-32 expression with α-SMA,TGF-β1, degree of renal pathological lesions and clinical index in IgAN was assessed by Spearman correlation analysis. Results RGC-32 protein located in renal tubular epithelial cells in normal and IgAN renal tissues. The positive expression index of RGC-32 in nomal group, IgAN mild group, moderate group and severe group was (18.29±6.22)%, (23.90±9.65)%, (31.23±9.86)%,and (34.52±10.63)% respectively. With more severity of renal pathological lesions, the expression of RGC-32 in IgAN was enhanced. The RGC-32 expression was positively correlated with the score of glomerulus and renal interstitium in children with IgAN (r=0.385, 0.347, P＜0.05), as well as α-SMA, TGF-β1 (r=0.594, 0.521, P＜0.01), but was not correlated with Scr, urinary NAG/Cr,Alb/Cr, IgG/Cr, and α1-M/Cr (r =0.117, -0.115, -0.138, -0.176, -0.028, all P ＞0.05).Conclusions RGC-32 protein locates in renal tubular epithelial cells in normal and IgAN renal tissues. RGC-32 may participate in the course of renal tubulointerstitial lesions in children with IgAN, especially in the course of epithelial-mesenchymal transition (EMT) induced by TGF-β1.
ABSTRACT
Objective To investigate the typical value of gamma-radiation dose rate and its confidence interval in tank-transported copper ore by using bootstrap resampling techniques. Methods Bootstrap resampling method, coupled with kernel density estimation, introduced to acquire the typical value of gamma-radiation dose rate in copper ore. Results The typical value of gamma-radiation dose rate in copper ore was expressed as the central tendency of the means of resampling, and two kinds of confidence interval, empirical percentile and bias-corrected accelerated confidence interval, were provided as standard error. Conclusion It is clearly demonstrated that this method has an advantage to give a robust description in explanation of central tendency and variation range of gamma-radiation dose rate data profiles.
ABSTRACT
Objective To explore the inhibitory effect of decorin(DCN) on rat mesangial cell (MsC) growth and on the expression of mitogen-activated protein kinases (MAPKs) and p21 protein. Methods Lipofectin-mediated method was used to transfect DCN vector into MsC. After the screen and identification of transfected MsC, DCN-containing supernatant was collected and added into the culture medium of normal MsC, then flow cytometer was used to detect the cell cycle. Western blot analysis was used to explore the changes of MAPK and p21 protein. Immunofluorescence was adapted to detect the expression of p21 on cultured MsC. Results Compared with normal MsC, the number of G2-M cells treated with DCN-containing supernatant decreased to 35%(P
ABSTRACT
Objective To examine the expression of angiopoietin-like protein(ANGPTL)3 in kidneys from children with primary nephrotic syndrome. Methods Immunohistochemistry for ANGPTL3 was performed in kidney biopsies from patients with nephrotic syndrome or hematuria, including MCD (n=31), MN(n=6), FSGS (n=6), TBMN (n=10), IgA nephropathy (IgAN) with mesangial proliferation (n=16). Normal renal tissue of 2 cases with nephrectomy for tumor were used as control. According to the episode, four groups were divided ("12 months"). The expression was quantitatively examined with IMS color image analysis system, using positive index (PI) as sediment degree of ANGPTL3 in glomeruli or tubules. Immunofluorescence for ANGPTL3 co-labeling with WT1 and perlecan was applied to show the distribution of ANGPTL3. Results (1) The PI levels of ANGPTL3 in glomeruli of MCD(7.49?1.96) and MN (6.27?0.98) were significantly higher than those of TBMN (0.02?0.001), FSGS (3.14?0.49) or normal control(0.02?0.001) respectively (all P
ABSTRACT
Objective To explore whether the antagonistic effect of decorin (DCN)on progression of glomeruloselerosis is associated with the inhibition of the expression of type I and type II transforming growth factor-? receptors (TGF-?R I and TGF-?R II )in mesangial cells (MsC). Methods RT-RCR and Western blot analysis were used to detect the expression of TGF-?R I and TGF-?R II mRNA and their proteins on cultured rat MsC stimulated by exogenous TGF-?1. Lipofectin-mediated method was used to transfect DCN vector into MsC. After screening and identifying of transfected MsC, RT-PCR and Western blot analysis were adapted to detect the changes of TGF-?R I and TGF-?R II expression respectively. Results The expression of TGF-?R I and TGF-?R II mRNA and their proteins on normal MsC stimulated by exogenous TGF-?1 increased in time-dependent manner and reached the peak at 24th hour. Compared with normal and untransfected MsC (1P-1), the mRNA and protein expression of TGF-?R I and TGF-?R II on MsC (3D-5, 7D-1) transfecled by DCN gene decreased significantly, and DCN gene transfection could antagonize the increase of mRNA and protein expression of both receptors caused by exogenous TGF-?1. Conclusions The expression of both TGF-?R I and TGF-?R II decreases obviously in MsC overexpressing DCN gene, which may be one of the importan antagonistic mechanisms of decorin involved in the development of glomeruloselerosis mediated by TGF-?.
ABSTRACT
Three widely used methods of sediment toxicity evaluation were introduced in the present paper, including organism toxicity tests, toxicity identification evaluation(TIE) and sediment quality guidelines(SQGs). Compared with the chemical analysis, toxicity tests have an advantage of taking the bioavailability of POPs into account, however, it fails to identify the causative toxicants. TIE, integrating with physicochemical analysis, implicates the specific pollutants in a tiered approach, and by which effective remediation can be designed accordingly. The sediment toxicity can be identified more quickly and appropriately by SQGs than by the former two methods. The differences among the different SQGs constituted by different standards may affect their values for toxicity evaluation. Extensive and reliable SQGs had been acquired to improve their utility. Finally, the combination of chemical analysis, toxicity tests and in situ bioassays will be the trend of sediment toxicity evaluation in the future.