[Therapeutic method of integrated traditional Chinese and Western medicine in treating patients with pancreatic pseudocyst and abscess: a report of 4 cases].
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Publications and source records attributed to Ning Zhang.
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OBJECTIVE: To compare the prognostic efficacy of three clinical staging systems: the Chinese system (CS), CLIP scores, and TNM for hepatocellular carcinoma (HCC). METHODS: 107 cases diagnosed as HCC between January 2000 and October 2003 were retrospectively analyzed. Their clinical stages were decided on the basis of data in CLIP or Chinese staging system when the HCC diagnosis had been confirmed. Fifty-three of the 107 patients underwent surgical resection. The TNM stage was therefore determined according to surgico-pathological results. The survival of those patients with respective to different stages were analyzed and compared using Kaplan-Meier curves and Log rank method. RESULTS: All the patients were followed up after treatment. The 3-year survival rate in the CS Ia, Ib and CLIP 0 group were 100%. The 1- and 2-year survival rates of CS IIIa group was 68% and 51%, respectively. The 1-year survival in CS IIIb group was only 20.9%. The 1-, 2-, and 3-year survival rate in patients with a CLIP score beyond 4 was 57.1%, 49.9%, and 33.5%, respectively. In patients treated with surgical resection, the CS Ia group and TNM I group had a 3-year survival rate of 100%. The 1- and 3-year survival rate in CS IIb were 83.3% and 75.0%, in TNM III group 93.7% and 77.5%. CONCLUSION: The CLIP system may provide accurate prediction of prognosis based on early clinical features. The CS system is comparably efficient in predicting the prognosis of HCC patients, particularly in patients with severe cirrhosis.
OBJECTIVE: To establish a nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver, and to serve researches on pathogenesis and experimental treatment of this disease. METHODS: Small pieces of lymphoma tissues freshly taken from patients with primary lymphoma of the liver were orthotopically transplanted into the liver parenchyma in nude mice. Tumorgenicity, invasion, metastasis, and morphological characteristics were examined by light and electron microscopy and immunohistochemistry. AFP, HBsAg and LDH were assayed by serological test. Karyotype analysis and DNA content of orthotopically transplanted tumors were also performed. RESULTS: A nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver was successfully established and named HLBL-0102. The tumor was confirmed as primary lymphoma of the liver (non-Hodgkin's lymphoma, B cell) by histopathology. Immunohistochemistry showed positive expression of CD19, CD20, CD45 and CD79a, but negative of CD3 and CD7. Serological test indicated that AFP was negative, HBsAg positive and the concentration of LDH was 1267.5 U/L. The number of chromosomes was between 55 and 59. DNA index (DI) was 1.57 approximately 1.61 (i.e. heteroploid). So far, the strain HLBL-0102 has grown for 3 years and been passaged for 37 generations in nude mice. Totally 283 nude mice were used for transplantation and the successful rate was 100%. Both the growth rate and resuscitation rate of liquid nitrogen cryo-preserved transplanted tumors were 100%. The transplanted tumors grew intensely and invasively in the liver of nude mice and damaged adjacent liver tissues, bile ducts and portal vein areas. No involvement of other tissues and organs and distal lymph nodes was observed. CONCLUSION: To our knowledge it is the first report of successfully established nude mouse model of orthotopically transplanted human primary malignant lymphoma of the liver. The HLBL-0102 model simulate very well the natural process of human primary lymphoma of the liver and provides an ideal animal model for researches on the biology and therapies of this malignancy.
OBJECTIVE: To provide an ideal animal model for exploring pathogenesis and experimental treatment of primary colonic lymphoma. METHODS: Primary colonic and liver metastatic lymphoma tissues were obtained from the surgical specimens,and transplanted into colonic mucosa of nude mice respectively. The tumorigenesis, invasion, metastasis and morphology of the transplanted tumor were observed. Karyotype was analyzed and DNA content was measured. RESULTS: According to the new WHO classification of malignant lymphoma, two high metastatic models (HCBL-0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human primary colonic non-Hodgkin's B cell lymphoma in nude mice were established successfully by orthotopic transplantation. Pathological examination showed poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors, and immunohistochemical staining showed positive expressions of CD19, CD20 and CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL-0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%. However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%. The transplanted tumors grew autonomously and invasively in nude mice, and further developed hematogenous, lymphatic metastasis and intraperitoneal seeding. CONCLUSIONS: HCBL-0303 and HCBL-0304 are the first established high metastatic models of primary colonic lymphoma, and can be applied to the research on pathogenesis, invasion,metastasis and experimental therapy of human primary colonic lymphoma.
OBJECTIVE: Conducting a meta-analysis to evaluate the efficacy of artificial liver support system (ALSS) in the treatment of hepatic failure in China. METHODS: Clinical trials comparing ALSS vs. routine medical treatment of hepatic failure in China were identified from computer-based literature. The pooled odds ratio and 95% confidence interval (CI) of prognostic indicators, such as survival rate and clinical improvement rate at discharge, were used to measure the magnitude of the efficacy. RESULTS: Ten trials including 1030 patients were identified. The odds ratio (95% CI) of survivorship or improvement of ALSS over routine medical treatment in early, intermediate and advanced stages of hepatic failure were 3.72 (2.03-6.83), 2.79 (2.88-4.14) and 1.85 (0.96-3.56) respectively. CONCLUSION: ALSS treatment is more effective in early and intermediate stages of hepatic failure than routine medical treatment, but not in its advanced stage.
OBJECTIVE: To evaluate the clinical manifestation, management and prognostic characteristics of scrotal extramammary Pagets disease (EMPD). METHODS: Twenty-three cases of EMPD were identified and retrospectively reviewed, and the clinical findings, surgical treatment, pathologic features and prognostic characteristics were evaluated. The patients ranged in age from 49 to 72 years (mean 62. 4 years). The diagnoses were delayed by 12 to 132 months (67. 6 on average) in 9 cases at Stage A1 , 12 at A2, 1 at B and 1 at D. The rate of initial misdiagnosis was 91.3% (21/23). Twenty of the patients underwent operations, 2 received radiotherapy and 1 chemotherapy. RESULTS: Twenty-two patients of the total number were followed up for 7 to 223 months, averaging at 119, therapy and 1 chemotherapy. of whom 12 remained cancer free, 1 died of tumor, 3 died of intercurrent disease, 4 experienced local recurrence, 1 relapsed with inguinal lymph node metastasis and 1 developed inguinal lymph node metastasis exclusively. Those with relapses received the second surgery, and 5 of them survived without cancer and 1 died of intercurrent disease. CONCLUSION: The primary treatment of choice for scrotal EMPD is radical excision. Precise, histological examination before and during the operation is of crucial importance. The positive excisal margins are one of the key causes of local recurrence, and the involvement of dermis by Pagets cells may suggest possible metastasis. Scrotal EMPD tends to occur as a slowly growing lesion, mainly in the elderly, and has a good prognosis in cases of non-invasion. Otherwise the prognosis is poor.
Based on the progress in the world market of drug delivery system (DDS) product and the research profile of DDS of compound Chinese Medicine, The article puts forward a new method of studies on DDS of compound Chinese Medicine. It is expected that the theory of compatibility of compound Chinese Medicine can be shown and its role can be exerted to the largest extent with the application of pharmaceutics technology to change the mode of drug delivery of activated components of compound Chinese Medicine.
In order to improve the guidance potential of a nerve entubulation bridging device, highly aligned textures were formed on the inner surface of semipermeable hollow fiber membranes (HFMs) during the wet phase inversion process. By precisely controlling the fabrication parameters, such as polymer solution flow rate, coagulant solution flow rate, and the air-gap distance, also called drop height, different-sized aligned grooves can be fabricated on the inner surface of HFMs. Preliminary studies using in vitro dorsal root ganglion (DRG) regeneration assay showed that both the alignment and outgrowth rate of regenerating axons increased significantly on HFMs with aligned textures compared to those on HFMs with a smooth inner surface. Studies in progress are evaluating axonal outgrowth and regeneration using in vivo sciatic-nerve and spinal-cord-injury models.
As part of our structure-activity relationship studies, we report here the synthesis and in vitro anti-HBV and anti-HCV activities of a number of ring-expanded ('fat') nucleobases containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system. One of the compounds, ZP-88, exhibited a good activity/toxicity profile against HBV by inhibition of the synthesis of extracellular virion release (EC(50)=1.7microM, CC(50)=286microM, SI=168) and intracellular HBV replication intermediates (EC(50)=8.4microM, CC(50)=286microM, SI=34) in cultured human hepatoblastoma 2.2.15 cells. By contrast, most of the compounds tested against HCV had only marginal activity/toxicity profile, although that was still better than that of the reference compound ribavirin.
IkappaBalpha is an inhibitor of the nuclear transcription factor NF-kappaB. Binding of IkappaBalpha to NF-kappaB inactivates the transcriptional activity of NF-kappaB. Expression of IkappaBalpha itself is regulated by NF-kappaB, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo IkappaBalpha expression by imaging IkappaBalpha-luc transgenic mice for IkappaBalpha promoter driven luciferase activity. We demonstrated a rapid and systemic induction of IkappaBalpha expression in the transgenic mice following treatment with LPS. The induction was high in liver, spleen, lung and intestine and lower in the kidney, heart and brain. The luciferase induction in the liver correlated with increased IkappaBalpha mRNA level. Pre-treatment with proteasome inhibitor bortezomib dramatically suppressed LPS-induced luciferase activity. The p38 kinase inhibitor SB203580 also showed moderate inhibition of LPS-induced luciferase activity. Analysis of IkappaBalpha mRNA in the liver tissue showed a surprising increase of the IkappaBalpha mRNA after bortezomib and SB203580 treatments, which could be due to increased IkappaBalpha mRNA stability. Our data demonstrate that regulation of IkappaBalpha expression involves both the NF-kappaB and the p38 signaling pathways. The IkappaBalpha-luc transgenic mice are useful for analyzing IkappaBalpha expression and the NF-kappaB transcriptional activity in vivo.
Chemokine receptors, a family of Gi protein-coupled receptors responsible for cell migration, are widely expressed by cells of immune and nervous systems. Activation of receptors on the surface of leukocytes, such as opioid, vasoactive intestinal peptide, or adenosine receptors, often has inhibitory effects on chemokine receptors by a mechanism termed heterologous desensitization, resulting in suppression of immune responses. Conversely, activation of chemokine receptors also induces heterologous desensitization of mu-opioid receptors (MOR), a class of key analgesic receptors on neurons. Furthermore, prior exposure of neuronal cells to chemokine treatment enhances the sensitivity of transient receptor potential vanilloid 1 (TRPV1), a heat- and ligand-gated calcium channel, which is critical for sensing of pain. Consequently, during inflammation, activation of chemokine receptors on neurons contributes to hyperalgesia by inhibiting MOR and concomitantly sensitizing TRPV1 via Gi protein-mediated signaling pathways. These observations suggest that the crosstalk between chemokine receptors and neuropeptide membrane receptors serves as a bridge between the immune and nervous systems.
BACKGROUND AND PURPOSE: Oxidative stress contributes to ischemia/reperfusion neuronal damage in a consecutive 2-phase pattern: an immediate direct cytotoxic effect and subsequent redox-mediated inflammatory insult. The present study was designed to assess the neuroprotective mechanisms of edaravone, a novel free radical scavenger, through antioxidative and anti-inflammatory pathways, from the early period to up to 7 days after ischemia/reperfusion in mice. METHODS: Mice were subjected to 60-minute ischemia followed by reperfusion. They were divided into the edaravone group (n=72; with different schedules for first administration) and the vehicle (control) group (n=36). Infarct volume and neurological deficit scores were evaluated at several time points after ischemia. Immunohistochemical analysis for 4-hydroxy-2-nonenal (HNE), 8-hydroxy-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba-1), inducible NO synthase (iNOS), and nitrotyrosine were performed at 24 hours, 72 hours, or 7 days after reperfusion. RESULT: Edaravone, even when administrated 6 hours after onset of ischemia/reperfusion, significantly reduced the infarct volume (68.10+/-6.24%; P<0.05) and improved the neurological deficit scores (P<0.05) at 24 hours after reperfusion. Edaravone markedly suppressed the accumulation of HNE-modified protein and 8-OHdG at the penumbra area during the early period after reperfusion (P<0.05) and reduced microglial activation, iNOS expression, and nitrotyrosine formation at the late period. CONCLUSIONS: Our results indicated that edaravone exerts an early neuroprotective effect through the early free radicals scavenging pathway and a late anti-inflammatory effect and suggested that edaravone is important for expansion of the therapeutic time window in stroke patients.
BACKGROUND AND PURPOSE: Social interaction can have a profound effect on health. The purpose of the present study was to determine whether affiliative social interactions before and after stroke improve ischemic outcomes as assessed through histological analysis and behavioral assays. METHODS: Male and female C57BL/6 mice were housed individually or with an ovariectomized female. Behavioral assessments were made 24 hours before 60 or 90 minutes of transient intraluminal middle cerebral artery occlusion (MCAO) or SHAM surgery and after 7 days of reperfusion. Two hours after behavioral testing on day 7, infarct size was determined by 2,3,5-triphenyltetrazolium histology, and blood samples were collected for assessment of corticosterone and C-reactive protein (CRP) concentrations. RESULTS: Pair housing significantly decreased infarct size and improved contralateral paw use in 60-minute MCAO males and 90-minute MCAO females compared with socially isolated cohorts. Housing condition had no significant effect on infarct size in females that underwent 60 minutes of MCAO, but pair housing was associated with improved contralateral paw use relative to socially isolated mice. In a separate cohort of males, intraischemic CRP concentration was significantly reduced in pair-housed males relative to isolated males. CONCLUSIONS: Affiliative interaction during the peri-ischemic period reduces intraischemic CRP concentration, decreases ischemic damage in male and female mice, and improves behavioral outcome.
The analysis of tandem mass (MS/MS) data to identify and quantify proteins is hampered by the heterogeneity of file formats at the raw spectral data, peptide identification, and protein identification levels. Different mass spectrometers output their raw spectral data in a variety of proprietary formats, and alternative methods that assign peptides to MS/MS spectra and infer protein identifications from those peptide assignments each write their results in different formats. Here we describe an MS/MS analysis platform, the Trans-Proteomic Pipeline, which makes use of open XML file formats for storage of data at the raw spectral data, peptide, and protein levels. This platform enables uniform analysis and exchange of MS/MS data generated from a variety of different instruments, and assigned peptides using a variety of different database search programs. We demonstrate this by applying the pipeline to data sets generated by ThermoFinnigan LCQ, ABI 4700 MALDI-TOF/TOF, and Waters Q-TOF instruments, and searched in turn using SEQUEST, Mascot, and COMET.
OBJECTIVE: To investigate the changes of gene expression in early stage of hemitransection of spinal cord and the regulatory effects of the traditional Chinese mixture Suifukang (SFK) on these changes. METHODS: Eighty-six adult male SD rats were randomly divided into 3 groups: Suifukang group (Group S, n = 31, administered with SFK 3 days before the hemitransection at the dose of 2.5 g crude drugs/100 kg body weight QD and then 4 h and 8 h after hemitransection), model group (Group M, n = 45, administered with normal saline in the manner as in Group S), and normal control group (Group N, n = 10, without any treatment). The rats of Groups S and M underwent hemitransection of spinal cord at the level T12 three days before treatment. Twenty-four hours after the spinal cord injury (SCI), the rats were anesthetized and the injured tissues of Groups S and M and the corresponding tissues of Group N were removed. Total RNA was extracted, mRNA was purified and marked by Cy3 or Cy5 fluorescence labeling to synthesize cDNA hybridized probe that was hybridized with Biostars gene chip. Then the chip was scanned with ScanArray500 scanning apparatus. The data were analyzed by Imagene3.0 software. RESULTS: There were 139 differentially expressed genes in Group M, 83 up-regulated and 56 down-regulated, involved in multifarious functions, such as cell metabolism, especially lipid metabolism, and regulation of ionic channel, immunity and defense, cytoskeleton protein, extracellular matrix, cell cycle, etc. There were 37 differentially expressed gene in Group S, 11 up-regulated, such as such Anxal, Ca(2+)-ATPase, IL-1 beta, Ofp, and 26 down-regulated, such as HSP-70 and Psap, several being key genes related to protection and regeneration of neuron. CONCLUSION: In the early stage after SCI many genes related to nervous degeneration, necrosis, traumatic inflammation, secondary injury of spinal cord, and aborted regeneration, etc, are expressed differentially. SFK regulates the changes of gene expression induced by SCI, thus initiating the protective effect of nervous tissues and promoting and supporting the regeneration of injured nervous tissues.
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a multifunctional tumor suppressor, has been shown to play a regulatory role in cell migration. Dictyostelium discoideum cells lacking PTEN exhibited impaired migration toward chemoattractant gradients. In the present study, we investigated the involvement of PTEN in chemotaxis of mammalian cells by examining PTEN-null Jurkat T cells. We observed that, in contrast to observations made in D discoideum, PTEN-null Jurkat T cells exhibited potent chemotactic responses to the chemokine stromal cell-derived factor 1alpha (SDF-1alpha), indicating that PTEN was not requisite for CXC chemokine receptor 4 (CXCR4)-mediated chemotaxis of Jurkat cells. Conversely, reconstitution of PTEN in Jurkat cells by using a tetracycline (Tet-on)-inducible expression system down-regulated CXCR4-mediated chemotaxis. Furthermore, we established the lipid phosphatase activity of PTEN as essential for its inhibitory effect on chemotaxis. In addition, using PTEN-expressing T-cell lines and primary T cells, we demonstrated that down-regulation of PTEN expression with vector-based small interfering RNAs (siRNAs) enhanced CXCR4-mediated chemotaxis. Based on these results, we conclude that PTEN expression negatively regulates chemotaxis of lymphoid mammalian cells via its lipid phosphatase activity. Our findings may account for the reported increase in metastatic activity of PTEN-null tumor cells.
PURPOSE: To investigate the role of neutrophils in the development of laser induced experimental choroidal neovascularization (CNV). METHODS: CNV was induced by laser photocoagulation in adult male C57BL/6J mice. Neutrophil infiltration was evaluated by histology and confocal immunohistology. The expression of neutrophil chemotactic chemokines in the regions of laser injury was determined by quantitative real-time PCR. Animals were treated with NIMP-R14, an anti-murine neutrophil monoclonal antibody (mAb), intraperitoneally to deplete neutrophils. The specific neutrophil depletion was confirmed by flow cytometry. The CNV responses were compared between neutropenic and untreated control mice on the basis of fluorescein angiography (FA), CNV lesion volume and lesion histology, and vascular endothelial growth factor (VEGF) expression by ELISA. Expression of VEGF and Angiopoietin-1 and Angiopoietin-2 protein by murine neutrophils was evaluated by confocal immunohistochemistry. RESULTS: Neutrophils infiltrated the sites of laser injury as early as day 1 after laser treatment and peaked at day 3. The neutrophil infiltration correlated with enhanced mRNA expression of neutrophil chemotactic chemokines MIP-2 and KC in the lesions. Administration of NIMP-R14 mAb specifically depleted neutrophils. Analysis of FA, CNV volume, and lesion histology, all demonstrated a moderate decrease in the CNV response in neutropenic mice compared to control mice (p<0.01). The reduction in the CNV response in neutropenic mice was associated with decreased VEGF protein levels in the ocular posterior segment. Murine neutrophils contained VEGF and Angiopoietin-1 and Angiopoietin-2 proteins. CONCLUSIONS: Neutrophil invasion was part of early inflammatory responses during laser induced CNV. Neutrophil depletion correlated with reduced CNV responses and decreased VEGF protein expression. These data suggest that neutrophils promoted the early development of CNV possibly via secretion of angiogenic growth factors.
Acute phase serum amyloid A proteins (A-SAAs) are multifunctional apolipoproteins produced in large amounts during the acute phase of an inflammation and also during the development of chronic inflammatory diseases. In this study we present a Saa1-luc transgenic mouse model in which SAA1 gene expression can be monitored by measuring luciferase activity using a noninvasive imaging system. When challenged with LPS, TNF-alpha, or IL-1beta, in vivo imaging of Saa1-luc mice showed a 1000- to 3000-fold induction of luciferase activity in the hepatic region that peaked 4-7 h after treatment. The induction of liver luciferase expression was consistent with an increase in SAA1 mRNA in the liver and a dramatic elevation of the serum SAA1 concentration. Ex vivo analyses revealed luciferase induction in many tissues, ranging from several-fold (brain) to >5000-fold (liver) after LPS or TNF-alpha treatment. Pretreatment of mice with the proteasome inhibitor bortezomib significantly suppressed LPS-induced SAA1 expression. These results suggested that proteasome inhibition, perhaps through the NF-kappaB signaling pathway, may regulate SAA1 expression. During the development of acute arthritis triggered by intra-articular administration of zymosan, SAA1 expression was induced both locally at the knee joint and systemically in the liver, and the induction was significantly suppressed by bortezomib. Induction of SAA1 expression was also demonstrated during contact hypersensitivity induced by topical application of oxazolone. These results suggest that both local and systemic induction of A-SAA occur during inflammation and may contribute to the pathogenesis of chronic inflammatory diseases associated with amyloid deposition.