Prognostic impact of tumor size on patients with neuroblastoma in a SEER-based study.

OBJECTIVE: The prognostic value of tumor size in neuroblastoma (NB) patients has not been fully evaluated. Our purpose is to elucidate the prognostic significance of tumor size in surgery performed on neuroblastoma patients. METHODS: Neuroblastoma patients diagnosed from 2004 to 2015 were selected from the Surveillance, Epidemiology, and End Results Program (SEER) for the study. Univariate and multivariate Cox proportional hazard regression models were used to identify risk factors and the independent prognostic influences of tumor size on NB patients. Overall survival (OS) was analyzed through univariate Cox regression analysis. To determine the optimal cutoff value of tumor size, we first divided the cohort into three groups (≤5 cm, 5-10 cm, >10 cm). Subsequently, the patients were divided into two groups repeatedly, with tumor size at 1 cm intervals. The cutoff value that maximized prognostic outcome difference was selected. Furthermore, we performed the Kaplan-Meier methods to visually present differences in prognosis between the optimal tumor size cutoff value in different subgroups. RESULTS: A total of 591 NB patients who met the inclusion criteria were selected from the SEER database in this study. Cox analysis showed that age >1 year (HR = 2.42, p < 0.0001), originate from adrenal site (HR = 1.7, p = 0.014), distant stage (HR = 6.4, p < 0.0001), undifferentiated grade (HR = 1.94, p = 0.002), and large tumor size (HR = 1.5, p < 0.0001) independently predicted poor prognosis. For tumor size, there were significant differences in tumor size distribution in different ages, tumor grade, disease stage, and primary site subgroup but not in sex, race, and histology subgroup. Furthermore, both univariate (HR = 4.96, 95% CI 2.31-10.63, p < 0.0001) and multivariable analysis (HR = 2.8, 95% CI 1.29-6.08, p < 0.0001) indicated the optimal cutoff value of tumor size was 4 cm for overall survival of NB patients. Using a 4 cm of tumor size cutoff in subgroups, we found that it can identify poor prognosis patients whatever their age or primary site. Interestingly, tumor size of 4 cm cutoff can only identify unfavorable NB patients with diagnosis at distant-stage disease, or differentiated grade tumor, but not with regional and local or undifferentiated tumor. CONCLUSIONS: Tumor size is first to be recognized as a key prognostic factor of neuroblastoma patients and a cutoff value >4 cm might predict poor prognosis, which should be included in the evaluation of prognostic factors for NB.

A Multidisciplinary Team Approach to the Treatment of Liver Cirrhosis.

OBJECTIVE: To explore the feasibility of treating cirrhosis using a multidisciplinary team approach (MDT) and to pinpoint the key factors influencing its implementation. METHODS: The data of 307 patients with decompensated cirrhosis were studied retrospectively. Patients who received more than two treatment measures were assigned to the MDT group (n=228), and patients who received symptomatic medical drug treatment only were assigned to the traditional treatment group (n=79). The follow-up period ranged from 4 to 10 years, and the average follow-up period was 5.7 years. The results of the biochemical tests for hepatitis B virus deoxyribonucleic acid, hepatitis C virus ribonucleic acid, and autoantibodies to liver disease were analyzed. RESULTS: The differences in gender and Child-Pugh grade of liver function between the two groups were not statistically significant. The MDT group had obvious advantages over the traditional treatment group in occupational composition, etiology composition, 5-year survival rate and annual hospitalization times. The leading causes of death in the MDT group, in descending order, were liver cancer, infection, mesenteric thrombosis, and non-hepatic disease, and, in the medical treatment group, they were liver failure, gastrointestinal bleeding, infection, and liver cancer. There was a significant statistical difference between the two groups (p < 0.05). In the multidisciplinary treatment, etiological treatment was the most widely used treatment, accounting for 79.8%, followed by endoscopic treatment (33.3%), peritoneal drainage and ascites reinfusion (25%), splenectomy combined with devascularization (11.4%) and stem cell transplantation and liver transplantation (1.8%). CONCLUSION: An MDT can improve the efficacy and prognosis of patients with cirrhosis and improve patient compliance. After multi-disciplinary intervention, the mortality spectrum of long-term survival patients with cirrhosis changes, and the mortality rate of liver cancer and non-liver disease increases.

Trends in research related to high myopia from 2010 to 2019: a bibliometric and knowledge mapping analysis.

AIM: To evaluate the global trends in and explore hotspots of high myopia (HM) research. METHODS: This bibliometric analysis was used to reveal the publication trends in HM research field based on the Web of Science Core Collection (WoSCC). VOSviewer version 1.6.13 software was used to analyze the data and construct a knowledge map including the yearly publication number, journals, countries, international collaborations, authors, research hotspots, and intellectual base in HM. RESULTS: The search engine found 3544 peer-reviewed publications on HM between 2010 and 2019, and the yearly research output substantially elevated over the past decade. China is the top publishing country, and Sun Yat-sen University was the most active academic institution. Jonas JB is the top publishing scientist, and Investigative Ophthalmology and Visual Science (IOVS) was the most productive journal. The highest cited references mainly focused on epidemiology and management. The keywords formed 6 clusters: 1) refractive surgery; 2) etiology and clinical characteristics; 3) the mechanism of eye growth; 4) management for myopic maculopathy; 5) vitrectomy surgical treatment; 6) myopia-associated glaucoma-like optic neuropathy. CONCLUSION: The evaluation of development trends based on the data extracted from WoSCC can provide valuable information and guidance for ophthalmologists and public health researchers to improve management procedures in HM field.

Visualisation of the vomerovaginal canal during endonasal transpterygoid approaches and CT imaging diagnosis.

The vomerovaginal canal (VVC) and palatovaginal canal (PVC) are two canals that open forward to the posterior wall of the pterygopalatine fossa (PPF). Although the anatomy and computed tomography (CT) appearances of the PVC have been well studied, the VVC has been rarely reported, especially in endoscopic examinations. Some studies have even failed to distinguish the PVC from the VVC on CT images. The purpose of this study was to demonstrate the anatomy of the VVC on endoscopy and reveal its differences from the PVC, and to analyse the relative positions of the VVC, PVC, and pterygoid canal on CT images. Ten dry skull bases were studied to observe the structures involved in the formation of the VVC. Dissection of four cadaveric heads was performed to demonstrate the anatomy of the VVC on endoscopy. Coronal CT image analysis in 70 patients was conducted to evaluate the distances and relative positions between the VVC, PVC, and pterygoid canal. The PVC and VVC were also compared on axial CT images. The osteological study showed the top wall of the VVC was the antero-inferior wall of the sphenoid sinus. The VVC may be a helpful landmark in endoscopic endonasal transpterygoid approaches. Steps and discrimination in the dissections of the VVC and PVC were described. The interval between the PVC and VVC could be observed on both coronal and axial CT images. The coronal CT images of patients showed differences in the positions and distances among the three canals at both the anterior and posterior apertures of the PVC. The VVC can be easily mistaken for the PVC if its existence is not suspected. The anatomical morphologies and trajectories of the VVC and PVC differed on both nasal endoscopy and CT. The existence of the VVC should be considered during surgery and CT diagnosis within this area.

Multimodal therapy and twenty years of valid management of a patient with chronic hepatitis B in a less developed Western Region in China---case report and review of the literature.

BACKGROUND: For patients with chronic hepatitis B and cirrhosis in less developed western regions in China, due to constraints of local economic conditions, the choice of treatment measures is often limited. However if patients recieved valid management and effective treatment, they were able to maintain their health and benign prognosis. CASE PRESENTATION: This study narrates the long-term treatment and careful follow-up of a patient with chronic hepatitis B and cirrhosis in a less developed western region in China, and analyzes the prognosis of the disease and countermeasures. CONCLUSIONS: This would partly reflect the development of antiviral therapy for chronic hepatitis B and multidisciplinary comprehensive treatment for cirrhosis-related complications in remote region with limited resources in the past 20 years.

Development and application of a PCR-HRM molecular diagnostic method of SNPs linked with TNF inhibitor efficacy.

Background Clinical evidence indicates that genetic variations may interfere with the mechanism of drug action. Recently, it has been reported that the single nucleotide polymorphisms (SNPs) of STAT4, PTPN2, PSORS1C1 and TRAF3IP2RA genes are associated with the clinical efficacy of tumor necrosis factor (TNF) inhibitors in the treatment of rheumatoid arthritis (RA) patients. Therefore, the detection of the SNPs linked with TNF inhibitor efficacy may provide an important basis for the treatment of RA. This study intended to establish molecular diagnostic methods for genotyping the linked SNPs based on high resolution melting (HRM) curve analysis. Methods The polymerase chain reaction-HRM (PCR-HRM) curve analysis detecting systems were established by designing the primers of the four SNPs, rs7574865G>T, rs7234029A>G, rs2233945C>A and rs33980500C>T, and the performance and clinical applicability of which were evaluated by using the Sanger sequencing method and genotyping test for 208 clinical samples. Results The self-developed molecular diagnostic methods of PCR-HRM were confirmed to be able to correctly genotype the four SNPs, the sensitivity and specificity of which were 100% in this study. The repeatability and reproducibility tests showed that there is little variable in intra-assay and inter-assay (the coefficient of variation ranged from 0.01% to 0.07%). The slight changes of DNA template and primer concentrations, PCR cycle number and reaction system volume had no significant effect on the genotyping performance of the method. The PCR-HRM assays were also applied to other PCR thermocyclers with HRM function and use different saturation fluorescent dyes. Conclusions The PCR-HRM genotyping method established in this study can be applied to the routine molecular diagnosis of rs7574865, rs7234029, rs2233945 and rs33980500.

Catechol-O-methyltransferase 158G/A polymorphism and endometriosis/adenomyosis susceptibility: A meta-analysis in the Chinese population.

PURPOSE: An association between catechol-O-methyltransferase (COMT) 158G/A polymorphism and endometriosis/adenomyosis susceptibility has been reported in the previous studies, but the results were inconsistent. This study was conducted to explore this association in the Chinese population using meta-analysis. MATERIALS AND METHODS: PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure, and Chinese Biology Medicine were searched for all relevant studies published up to December 2015. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. RESULTS: A total of 7 case-control studies including 782 cases and 700 controls were included in this meta-analysis. Overall, COMT 158G/A polymorphism was found to be significantly associated with endometriosis and adenomyosis risk in the Chinese population (A vs. G, OR = 1.21, 95% CI: 1.02-1.42; AA vs. GG, OR = 1.47, 95% CI: 1.01-2.14; AA vs. GG + GA, OR = 1.42, 95% CI: 0.99-2.03; AA + GA vs. GG, OR = 1.20, 95% CI: 0.97-1.49). In subgroup analyses stratified by ethnicity, source of controls and disease groups, the significant risk was found in Chinese not mentioned the ethnicity, in population-based studies and adenomyosis. CONCLUSIONS: COMT 158G/A polymorphism may contribute to the risk of endometriosis and adenomyosis in Chinese, particularly for adenomyosis.

miR-24-p53 pathway evoked by oxidative stress promotes lens epithelial cell apoptosis in age-related cataracts.

MicroRNA-24 (miR-24) serves an important role in cell proliferation, migration and inflammation in various types of disease. In the present study, the biological function and molecular mechanism of miR­24 was investigated in association with the progression of age­associated cataracts. To the best of our knowledge the present study is the first to report that the expression of miR­24 was significantly increased in human anterior lens capsules affected by age­associated cataracts as well as lens epithelial cells (LECs) exposed to oxidative stress. Overexpression of miR­24 induced p53 expression and p53 was verified as a direct target of miR­24. Overexpression of miR­24 enhanced LEC death by directly targeting p53. The present study revealed that oxidative stress induced the upregulation of miR­24 and enhanced LEC death by directly targeting p53. These results suggest that the miR­24­p53 signaling pathway is involved in a novel mechanism of age­associated cataractogenesis and miR­24 may be a useful therapeutic target for age-associated cataracts.

House dust mite allergens mediate the activation of c­kit in dendritic cells via Toll­like receptor 2.

Several studies have demonstrated that the c­kit proto­oncogene and its ligand, stem cell factor, are important in the development of asthma. House dust mite (HDM; Dermatophagoides pteronyssinus) allergens are a major trigger in the development and exacerbation of asthma. HDM allergens can induce the activation of c­kit in dendritic cells (DCs), leading to the development of allergic asthma. Previous studies have demonstrated that activation of Toll­like receptor 2 (TLR2) evokes a T helper (Th)2 immune response and promotes experimental asthma. The aim of the present study was to assess whether HDM mediates the activation of c­kit in DCs via TLR2. Monocyte­derived DCs were generated from C57BL/6 mice, and cultured with interleukin (IL)­4 and granulocyte­macrophage colony­stimulating factor. The DCs were then sensitized with HDM (10 µg/ml) for 72 h. TLR2­specific small interfering (si)RNA was used to silence and inhibit the expression of TLR2 in the DCs. The expression levels of c­kit and B7 (CD80/CD86) were measured, by analyzing the DC culture supernatant for the presence of IL­6 and IL­12. Inhibition of TLR2 using specific siRNA downregulated the expression of c­kit in the HDM­activated DCs. In addition, silencing of TLR2 inhibited the expression of CD80/CD86, decreased the production of IL­6, and increased the production of IL­12. These results indicated that TRL2 are important in the activation of c­kit by HDM in DCs.

Anti-inflammatory effects of propofol on lipopolysaccharides-treated rat hepatic Kupffer cells.

This study is set to explore the role of commonly used intravenous anesthetic propofol on the inflammatory response of rat liver Kupffer cells (KCs) induced by lipopolysaccharides (LPS). The isolated KCs were cultured at the density of 1 × 10(5)/ml, divided into five groups randomly after 48 h culture: group C, control group; group L, KCs were treated with 1 µg/ml LPS for 24 h; groups P1, P2, P3, KCs were pretreated with propofol at low (25 µM), medium (50 µM), high (100 µM) concentration for 2 h, respectively, and then were stimulated with 1 µg/ml LPS for 24 h. The expressions of tumor necrosis factor-α (TNF-α) mRNA and interleukin-1ß (IL-1ß) mRNA of every group were measured by RT-PCR. Nuclear NF-ΚB p65 was determined by Western blot. The concentrations of IL-1ß and TNF-α in supernatant were measured by ELISA. Compared with the group C, TNF-α mRNA and IL-1ß mRNA in group L were significantly up-regulated and NF-ΚB p65 was significantly up-regulated after LPS treatment (P < 0.05). Meanwhile, TNF-α and IL-1ß were also significantly increased (P < 0.05). With propofol the mRNA expressions of aforementioned inflammatory mediators were significantly down-regulated and NF-ΚB p65 was significantly inhibited in group P2 and P3 (P < 0.05), compared with group L. However, low propofol concentration did not exhibit any effect (group P1, P > 0.05). Propofol at medium and high concentration can counteract the LPS-induced inflammatory response in KCs by regulating NF-ΚB p65 protein expression.

[Effect of scalp acupuncture on learning ability and hippocampal VEGF expression in chronic cerebral ischemia rats].

OBJECTIVE: To observe the effect of scalp cluster-needle intervention on cognitive ability and hippocampal vascular endothelial growth factor (VEGF) expression in cerebral ischemia (CI) rats. METHODS: Forty Wistar rats were randomized into sham operation (sham), model, scalp-acupuncture and medication groups. Chronic CI model was established by occlusion of the bilateral common carotid arteries. Acupuncture needles were inserted into "Baihui" (GV 20) and its left and right points (2 mm beside GV 20) and manipulated leftward and rightward for 3 min at a frequency of about 200 times/min, retained for 30 min. The treatment was conducted once daily, for 4 weeks. For rats of the medication group, Nimodipine (1 mg/kg) was given to the animal by gavage, once a day, for 4 weeks. The rats' learning ability was measured by Morris water maze. Changes of hip-pocampal cellular morphology were observed by HE staining and light microscope, and hippocampal VEGF expression was detected by immunohistochemistry. RESULTS: In comparison with the sham group, the escape latency of rats in the model group was prolonged significantly (P < 0.05), suggesting a decrease of learning ability after CI. Compared with the model group, the escape latency of both acupuncture and medication groups were reduced markedly after the treatment (P < 0.05). In comparison with the sham group, the number of VEGF immunoreaction (IR) positive cells in the model group was up-regulated significantly (P < 0.05), while compared with the model group, the numbers of both acupuncture and medication groups were increased further (P < 0.05). No significant differences were found between the acupuncture and medication groups in escape latency and VEGF expression levels (P > 0.05). HE staining showed that in the model group the hippocampal pyramidal cells were reduced in number, became vaguer in layers and nucleole, and got deformed in structure with karyopycnosis and disappearance of endochylema, and cavitation. These situations were relatively lighter in both acupuncture and medication groups. CONCLUSION: Scalp acupuncture intervention can significantly improve CI rats' congnitive ability and pathological changes, which may be related to its function in increasing the expression of VEGF in the hippocampus.

[PKD3 contributes to up-regulation of prostate-specific antigen in prostate cancer cells].

OBJECTIVE: To investigate the role of PKD3 in prostate-specific antigen (PSA) expression regulation in androgen-dependent prostate cancer cells and explore the mechanism. METHODS: LNCaP cells containing low level of PKD3 were transfected with pEGFP-C2 or pEGFP-PKD3 plasmid followed by dihydrotestosterone (DHT) treatment, and PSA mRNA level was analyzed by RT-QPCR using 2(-delta delta Ct) method. Wild-type or kinase-dead PKD3 plasmids, human androgen receptor plasmid pSVAR0, pMMTV-luc of AR luciferase reporter and renilla luciferase reporter pRL-SV40 were cotransfected into HEK293 cells, and after treatment with DHT for 24 h, the cells were harvested and AR transcriptional activity were determined by dual-luciferase reporter assay. The subcellular localization of endogenous PKD3 and AR and their colocalization induced by DHT were observed by confocal microscopy. RESULTS: PSA mRNA level triggered by DHT was significantly increased by overexpression of pEGFP-PKD3 in LNCaP cells compared with that in pEGFP-C2 control cells (P<0.001). AR transcription in response to DHT treatment was also significantly up-regulated by wild type PKD3 expression (P<0.001), but partially down-regulated by kinase-dead PKD3 mutant (P<0.01). Endogenous PKD3 and AR in LNCaP cells not only translocated from the cytoplasm to the nucleus, but also colocalized with each other after DHT stimulation. CONCLUSION: Elevated AR transcriptional activity and enhanced expression of PSA induced by PKD3 in response to DHT treatment suggest that PKD3 contributes to the proliferation and malignant growth of androgen-dependent prostate cancer cells.

[Radiographic diagnosis of traumatic bronchial rupture].

OBJECTIVE: To study the X-ray and CT findings of traumatic bronchial rupture for early radiographic diagnosis and treatment. METHODS: The chest plain X-ray films and CT images of 21 patients with traumatic bronchial rupture confirmed by operations or bronchoscopy were retrospectively analyzed. RESULTS: The main radiographic findings of traumatic bronchial rupture included interrupted tracheobronchial air column, atelectasis, lung ptosis, pneumomediastinum and subcutaneous emphysema, pneumothorax or hydropneumothorax. CT scanning also revealed tracheobronchial wall defect, bronchostenosis, and bronchial occlusion, displacement and angulation. CONCLUSION: Chest plain X-ray film combined with CT scanning has important values for early diagnosis of traumatic bronchial rupture.

Antitumor effects of polysorbate-80 coated gemcitabine polybutylcyanoacrylate nanoparticles in vitro and its pharmacodynamics in vivo on C6 glioma cells of a brain tumor model.

Polybutylcyanoacrylate (PBCA) nanoparticles coated with polysorbate-80 have been extensively studied for delivery of drugs into the animal models; however, 1% polysorbate-80 coated gemcitabine PBCA nanoparticles (GCTB-PBCA-NPs) remain unknown. In this study, we investigated the inhibitory effects of brain targeted 1% polysorbate-80 coated GCTB-PBCA-NPs on C6 glioma cells in vitro and in vivo. GCTB-PBCA-NPs were prepared by emulsion polymerization and freeze drying. C6 glioma cells treated with 1% polysorbate-80 coated GCTB-PBCA-NPs showed poor growth with less cell density and increased detachment. Cell morphology was also greatly altered with nuclear vacuoles, ruptured cells and dead cells. Meanwhile, by flow cytometry, the numbers of cells treated with 1% polysorbate-80 coated GCTB-PBCA-NPs showed increase in G0/G1 phase and decreased in the S phase (P<0.01) compared with the blank control. CCK-8 assay also showed that GCTB could significantly inhibited cell proliferation in a concentration dependent manner. Finally, various preparations were injected (90 mg preparation per kg body weight) into the brain tumor model, which was produced after inoculating C6 glioma cells into Sprague Dawley (SD) rats for 14 days, it was shown that 1% polysorbate-80 coated GCTB-PBCA-NPs could significantly extend the survival time compared with the saline control (P<0.05). Taken together, 1% polysorbate-80 coated GCTB-PBCA-NPs can effectively inhibit the growth of C6 glioma cells in vitro and enhance antitumor activity on brain tumor in vivo.

[Comparative study on accumulation of Ah-receptor agonists in contaminated soil based on EROD bioassay and chemical analysis].

The potential ecological risk by wastewater or reclaimed water for irrigation is of great concerns in recent years, but little work was done on the chronic toxicities through long term accumulation of persistent organic chemicals in soil. In present work, concentration of Ah-receptor agonists in soil organic extract was measured by an ethoxyresorfin O-deethylase (EROD) bioassay, which was calibrated and expressed by the 2, 3, 7, 8-tetrachlorodibenzo- p-dioxin (2, 3, 7, 8-TCDD) toxic equivalent (TEQbio). Simultaneously, 16 PAHs in soil were analyzed and their TEQs (total as TEQ(PAHs)) were calculated according to their toxic equivalent factors (TEFs) cited from literature. By bioassay, it was found that the concentration level of Ah-receptor agonists in soil irrigated using reclaimed water could be as high as 97.4 ng/kg, which was obviously higher than that in background soil using ground water irrigation regime (56.0 ng/kg). In comparing the results from bioassay and chemical analysis, the percentage of TEQ(PAHs) in TEQbio increased from 10.3% in background soil to 78.6% in the soil irrigated by reclaimed water. Use of reclaimed water for irrigation could result in the accumulation of Ah-receptor agonists in soil,and a major part of them in this case could be attributed to the accumulation of 16 priority PAHs in soils.

[Screening of peptide inhibitors of acetylcholinesterase from 12-mer random phage display peptide library].

OBJECTIVE: To screen the peptide inhibitor of acetylcholinesterase (AChE) from 12-mer random phage display peptide library. METHODS: Human AChE was used as the target to screen its binding peptides from 12-mer random phage display peptide library. The positive phage clones were isolated after three rounds of biopanning followed then by sequence analysis and their activity evaluation. RESULTS: Six positive phage clones binding to human AChE were obtained, and 4 of them sharing the conservative sequence W(S/P)HY inhibited the enzyme activity of AChE. CONCLUSION: Acquisition of AChE inhibitor from phage display library provides clues for designing peptide inhibitors of AChE.

[Preparation of 10-hydroxycamptothecin semisolid lipid nanoparticles and investigation of its stability].

OBJECTIVE: To prepare 10-hydroxycamptothecin-semisolid lipid nanoparticles (HCPT-SSLN) and investigate its stability. METHODS: HCPT-SSLN was prepared by the method of "emulsion evaporation at a high temperature and solidification at a low temperature"; The morphology was examined by transmission electron microscope; The particle size and xi potential were determined by laser granularity equipment; The physical stability of both suspl and freeze drying powder of HCPT-SSLN were investigated. RESULTS: The mean particle size of the prepared HCPT-SSLN was 130.5 nm, drug loading was 2.51%, entrapment efficiency was 79.19%, xi potential was -33.1 mV; Placed at room temperature and 4 degrees C for 6 months, the appearance, particle size and entrapment efficiency of HCPT-SSLN were all stable. Moreover, the freeze drying powder was more stable than the suspl. CONCLUSION: The HCPT-SSLN has high entrapment efficiency and drug loading, uniform particle size, good stability, which initially indicates that HCPT is fit for being incorporated into SSLN.

Characterization of human gene encoding SLA/LP autoantigen and its conserved homologs in mouse, fish, fly, and worm.

AIM: To approach the elusive function of the SLA/LP molecule, we have characterized genomic organization and conservation of the major antigenic and functional properties of the SLA/LP molecule in various species. METHODS: By means of computational biology, we have characterized the complete SLA/LP gene, mRNA and deduced protein sequences in man, mouse, zebrafish, fly, and worm. RESULTS: The human SLA/LP gene sequence of approximately 39 kb, which maps to chromosome 4p15.2, is organized in 11 exons, of which 10 or 11 are translated, depending on the splice variant. Homologous molecules were identified in several biological model organisms. The various homologous protein sequences showed a high degree of similarity or homology, notably at those residues that are of functional importance. The only domain of the human protein sequence that lacks significant homology with homologous sequences is the major antigenic epitope recognized by autoantibodies from autoimmune hepatitis (AIH) patients. CONCLUSION: The SLA/LP molecule and its functionally relevant residues have been highly conserved throughout the evolution, suggesting an indispensable function of the molecule. The finding that the only non-conserved domain is the dominant antigenic epitope of the human SLA/LP sequence, suggests that SLA/LP autoimmunity is autoantigen-driven rather than being driven by molecular mimicry.

In vitro and in vivo effects of combination of Trastuzumab (Herceptin) and Tamoxifen in breast cancer.

Extensive interactions between estrogen receptor alpha (ERalpha) and HER2 signaling pathways have been described. Using BT-474 human breast cancer cells, we have previously shown that the combination of tamoxifen (TAM) and Herceptin results in strong synergistic growth inhibition, enhancement of G(0)-G(1) cell cycle accumulation, inhibition of HER2 activity and a cytostatic effect without cell death. To further examine the underlying mechanism of synergy, we investigated the effect of this drug combination on ERalpha function and growth factor downstream signaling. TAM caused a small increase in ERalpha levels while Herceptin had no effect, and both drugs caused an increase in the level of Ser118-phosphorylated ERalpha. However, both TAM and Herceptin individually inhibited ERalpha transcriptional activity, although the combination did not have a greater effect than either single agent. Herceptin inhibited MAPK and Akt activity, while TAM had no effect on these either as a single agent or when added to Herceptin. Using a BALB/c athymic BT-474 in vivo xenograft model, the drug combination (Herceptin 0.3 mg/kg i.p. twice weekly, TAM 1.0 mg/mouse i.p. three times per week) showed a greater inhibition of tumor growth compared to either single agent. Tumor extracts and fixed sections were examined at the end of the treatment period for treatment-specific alterations: we noted a paradoxical proliferation-inducing effect of TAM that was reversed by the addition of Herceptin. Our results indicate that combined targeting of both peptide growth factor receptors and ERalpha represents a promising breast cancer treatment strategy.

Effect of Changtong oral liquid on serum cytokine concentrations in rats with postoperative intestinal adhesion.

OBJECTIVE: To observe the effects of Changtong oral liquid (CTOL) on the serum levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta(1), interleukin (IL)-1beta, IL-4, IL-6 and IL-10 in rats with postoperative intestinal adhesions. METHODS: Fifty-four male Sprague-Dawley rats were randomized into 6 equal groups, namely the normal control, model, Simo decoction (SMD) groups and three CTOL groups of low, moderate, and high doses, respectively. Intestinal adhesion was induced in the rats of the groups other than the normal control group. The rats in the normal control and model groups received intragastric administration of distilled water (10 ml/kg), and those in the 4 treatment groups had SMD (10 ml/kg) and CTOL (at 4.3, 8.6 and 17.2 g/kg for low, moderate, and high dose groups, respectively). On day 7 after surgery, blood samples were obtained from the rats for measurement of serum cytokine levels with enzyme-linked immunosorbent assay followed by adhesion grading according to a 5-grade scale. RESULTS: CTOL evidently reduced the severity of postoperative adhesions and decreased the serum levels of the proinflammatory cytokines such as TNF-alpha, IL-1beta, TGF-beta(1) and IL-6. However, it had no significant impact on serum levels of the anti-inflammatory cytokines IL-4 and IL-10 in rats with postoperative adhesion. CONCLUSION: Significant indices for postoperative adhesion assessment are established, which provides the experimental basis for evaluating clinical therapeutic effects of postoperative adhesions as well as for developing new therapeutic drugs.