Showing papers by "Binzhou Medical College published in 2018"

LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration

Abstract: Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.

hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway.

Abstract: Human placenta-derived mesenchymal stem cell (hPMSC) transplantation has been demonstrated to be an effective way of recovering ovarian function in mice with autoimmune induced premature ovarian failure (POF). But the exact mechanism remains unclear. The goal of the present study is to investigate the role of immune factors (T-helper 17 (Th17), cytotoxic T (Tc17) and regulatory T (Treg) cells) in the recovery of ovarian function and whether the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway is involved in the regulation. The inhibitor of PI3K/Akt was administered to observe its effect on ovarian function recovery and immune regulation. Serum levels of estradiol (E2), follicle stimulation hormone (FSH), luteinizing hormone (LH) and anti-Mullerian hormone (AMH)) and anti-Zona pellucida antibody (AZPAb) were measured by ELISA to evaluate ovarian function. The morphological changes of ovaries were observed by HE staining. Apoptosis of granular cells (GCs) was determined by detecting the expression of capase-3. Expression of p-Akt protein was detected by immunohistochemistry and western blot assay in ovarian tissues. The MTT assay was performed to assess GC proliferation. GC apoptosis was performed using flow cytometry analysis. Percentages of Th17, Tc17 and Treg cells were detected by flow cytometry. Expression of interleukin (IL)-17 in serum was measured by ELISA. LY294002 administration decreased serum levels of E2 and AMH, while the levels of FSH, LH and AZPAb in serum were increased compared with mice in the hPMSC transplantation group. The ovarian morphology presented as atrophy and fibrosis, with functional follicles exhausted. The expression of p-Akt in ovarian tissue was significantly decreased. Also, LY294002 administration significantly decreased proliferation and increased cell apoptosis in GCs, and for immune factors the ratios of Th17/Tc17 and Th17/Treg cells were significantly increased, as well as the serum levels of IL-17. Our data suggest that the PI3K/Akt signal pathway is involved in the recovery of ovarian function by changing the ratios of Th17/ Tc17 and Th17/Treg cells in POF mice following hPMSC transplantation.

Suppression of autophagy and HCK signaling promotes PTGS2high FCGR3- NK cell differentiation triggered by ectopic endometrial stromal cells.

Abstract: Impaired NK cell cytotoxic activity contributes to the local dysfunctional immune environment in endometriosis (EMS), which is an estrogen-dependent gynecological disease that affects the function ...

CUL4B promotes gastric cancer invasion and metastasis-involvement of upregulation of HER2

Abstract: Cullin 4B (CUL4B) is a scaffold protein overexpressed in several solid malignancies. It is known to silence tumor suppressor through post-transcriptional manner. However, its clinical significance and underlying molecular mechanisms in gastric cancer (GC) remain largely unknown. In this study, we found that CUL4B was significantly overexpressed in GC tissues and its overexpression was correlated with lymph node metastasis and poor prognosis. Through gain- and loss-of-function experiments, we showed that CUL4B promotes GC cell invasion and epithelial-mesenchymal transition (EMT) in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we identified HER2 as a downstream target gene of CUL4B in GC. CUL4B unregulated HER2 expression via transcriptionally repressing miR-125a. Intriguingly, HER2 inhibitors significantly reversed CUL4B-induced EMT in vitro and partially blocked GC metastasis in tumor xenografts with CUL4B overexpression. Finally, we suggested the involvement of the PI3K/AKT pathway in CUL4B-induced HER2 upregulation in GC. In all, we proposed a model for a CUL4B-miR-125a-HER2 oncoprotein axis, which provided novel insight into how HER2 was activated and contributed to GC progression and metastasis.

Interleukin-35 Inhibits TNF-α-Induced Osteoclastogenesis and Promotes Apoptosis via Shifting the Activation From TNF Receptor-Associated Death Domain (TRADD)-TRAF2 to TRADD-Fas-Associated Death Domain by JAK1/STAT1.

Abstract: Over-activated osteoclasts derived from myeloid or peripheral blood monocytes by inflammatory cytokines results in osteoporosis, osteoarthritis, and other bone erosion-related diseases. Interleukin 35 (IL-35) is a novel anti-inflammatory and immunosuppressive factor. This study investigated the effect of IL-35 on TNF-α-induced osteoclastogenesis. In the presence of IL-35, this process was detected by Tartrate-Resistant Acid Phosphatase (TRAP) staining, F-actin staining, and bone resorption assays. The effects of IL-35 on TNF-α-induced apoptosis were demonstrated by TUNEL staining, cell viability assays, and flow cytometry. Moreover, a microarray was performed to detect the effect of IL-35 on TNF-α-activated phosphatase kinase. The effect of IL-35 on the TNF-α-mediated activation of NF-κB, MAPK, TRAF2, RIP1, Fas-associated death domain (FADD), and caspase3 was further investigated. In addition, a murine calvarial osteolysis model was established via the subcutaneous injection of TNF-α onto the calvaria, and histological analysis was subsequently performed. As a result, IL-35 inhibited TNF-α-induced osteoclast formation and bone resorption in vitro and osteolysis calvaria in vivo. NFATc1, c-fos, and TRAP were downregulated by IL-35 through the inhibition of NF-κB and MAPK, during which JAK1/STAT1 was activated. Moreover, based on TUNEL staining and flow cytometry, IL-35 was shown to enhance TNF-α-induced osteoclast apoptosis. Meanwhile, FADD and cleaved-caspase 3 were increased in cells treated with TNF-α and IL-35, whereas the DNA-binding activity of NF-κB was increased in TNF-α-treated cells, but was decreased in cells treated with both TNF-α and IL-35. In conclusion, IL-35 inhibits TNF-α-induced osteoclastogenesis and promotes apoptosis by activating JAK1/STAT1 and shifting activation from TNF receptor-associated death domain (TRADD)-TRAF2/RIP1-NF-κB to TRADD-FADD-caspase 3 signaling.

CLDN2 inhibits the metastasis of osteosarcoma cells via down-regulating the afadin/ERK signaling pathway

Abstract: In an earlier study, we investigated the expression of tight junction protein claudins (CLDNs) in human osteosarcoma (OS) cells, and the CLDN2 was found to be down-regulated in primary tumor cells compared with normal osteoblast cells. Here, we sought to explore the effects of CLDN2 on the malignant phenotype of OS and the underlying molecular mechanisms. The expression patterns of CLDN2 and afadin in OS tissues and histologically non-neoplastic bone tissues were explored via immunohistochemistry and western blotting. CLDN2 expression levels in an OS cell line stably expressing CLDN2 and an osteoblast cell line with a CLDN2 knockout were confirmed by western blotting and immunofluorescence staining. The malignant phenotype of OS cells and osteoblast cells in vitro was assessed using a cell counting kit-8 assay, transwell assay and wound-healing experiment. Western blotting was utilized to detect the activation state of Ras/Raf/MEK/ERK pathway. Moreover, an RNA interference method were used to silence afadin in CLDN2-expressing OS cells. Our research group found that CLDN2 and afadin was underexpressed in OS tissues, and the overexpression of CLDN2 significantly inhibited the migration abilities of OS cells. Genetic silencing of afadin in CLDN2-overexpressing OS cells promoted U2OS cell motility and activation of the Ras/Raf/MEK/ERK pathway. In this study, we confirmed that CLDN2 expression significantly inhibited the malignant phenotype of OS cells in vitro. Inhibition of the ERK pathway by afadin may be one of the mechanisms by which CLDN2 blocks the metastasis phenotype of OS cells.

Anticancer effect of exogenous hydrogen sulfide in cisplatin‑resistant A549/DDP cells

Abstract: Despite huge advances in lung cancer treatment, resistance to cisplatin‑based chemotherapy remains one of the major obstacles, and the elucidation of cisplatin resistance remains challenging. As an important biological and pharmacological mediator, hydrogen sulfide (H2S) performs a variety of homeostatic functions related to cancer formation and development. However, the effects of H2S on cisplatin‑resistance lung cancer remain largely unknown. In the present study, we investigated the anticancer effects and relevant mechanisms of NaHS (an exogenous donor of H2S) on A549/DDP cells (cisplatin‑resistant). The intracellular H2S was first evaluated using a fluorescence probe in A549 (cisplatin‑sensitive) and A549/DDP cells. We found that H2S production was markedly decreased in A549/DDP cells compared with that in A549 cells, accomplished by the downregulation of cystathionine β‑synthase (CBS), an endogenous H2S‑producing enzyme. In view of these findings, we then observed the effects of NaHS treatment on A549/DDP cells. The results showed that NaHS exposure exhibited an inhibitory effect on cell viability and the IC50 of cisplatin in A549/DDP cells decreased markedly during NaHS treatment (800 µmol/l). In addition, our data revealed that NaHS treatment of A549/DDP cells resulted in the induction of apoptosis, cell cycle arrest and inhibition of cell migration and invasion. Finally, we demonstrated that the marked changes in the A549/DDP cell response to NaHS may be triggered by the activation of p53, and overexpression of p21, caspase‑3, Bax and MMP‑2, as well as the downregulation of Bcl‑xL. The findings of the present study provide novel evidence that NaHS administration may represent a new strategy for the treatment of cisplatin‑resistant lung cancer.

Preeclampsia and maternal risk of breast cancer: a meta-analysis of cohort studies.

Abstract: Background: Pregnancy-related hypertensive disorders, including preeclampsia (PE) and pregnancy-induced hypertension (PIH), may influence the maternal risk of breast cancer. However, results of the cohort studies were inconsistent.Methods: An updated meta-analysis of cohort studies was performed to evaluate the association between PE, PIH and maternal breast cancer incidence. Relevant studies were identified via searching of PubMed and Embase databases. A random effect model was applied to synthesize the results. Stratified analyses were performed to evaluate the potential influence of parity, gender of offspring, and study design on the association between PE and maternal breast cancer incidence.Results: Ten cohort studies with 2,417,899 pregnant women were included. Maternal risk of breast cancer was not significantly affected by PE (risk ration [RR] = 0.93, 95% confidence interval [CI]: 0.82–1.06, p = .27), or PIH (RR = 0.95, 95% CI: 0.81–1.12, p = .54). Interestingly, PE was associated with si...

DNA methylation enzyme inhibitor RG108 suppresses the radioresistance of esophageal cancer.

Abstract: Esophageal cancer (EC) is the eighth most common highly aggressive cancer worldwide. The purpose of this study was to investigate the effect of the DNA methyltransferase inhibitor RG108 on the radiosensitivity of EC cells. MTT and clonogenic assays were performed to assess the effect of RG108 on the proliferation and radiosensitivity of Eca‑109 and TE‑1 human EC cells. The cell cycle progression and alterations in apoptosis were analyzed by flow cytometry. For the in vivo analysis, the Eca‑109 cells were inoculated into nude mice to establish tumors. Tissues from xenografts were obtained to detect changes to microvessels and tumor growth by immunohistochemistry (IHC). RNA-seq was used to identify differentially expressed genes. We found that RG108 increased the radiosensitivity of EC cells. Apoptosis and G2/M-phase arrest were induced by X-ray irradiation and were significantly enhanced by RG108. In addition, growth of tumor xenografts from the Eca‑109 cells was significantly inhibited by irradiation in combination with RG108. The RNA-seq analysis revealed that, compared with radiation alone, X-ray irradiation in combination with RG108 altered the expression of 121 genes in multiple pathways, including the TGF-β signaling pathway and the Epstein-Barr virus infection pathway. In conclusion, RG108 induced radiosensitivity in EC cells both in vitro and in vivo.

Microwave ablation for lung cancer patients with a single lung: Clinical evaluation of 11 cases

Abstract: Background The study was conducted to retrospectively evaluate the safety and effectiveness of computed tomography (CT)-guided percutaneous microwave ablation (MWA) for peripheral non-small cell lung cancer (NSCLC) in 11 patients with a single lung after pneumonectomy. Methods From May 2011 to March 2015, 11 single-lung patients (8 men and 3 women; mean age 60.3 years, range 46-71) with peripheral NSCLC underwent 12 sessions of MWA. Eleven tumors measuring 13-52 mm (mean 30.2 mm) were treated. Follow-up was performed via CT scan at 1, 3, 6, 12, 18, and 24 months after the procedure and annually thereafter. Clinical outcomes were evaluated and complications after MWA were summarized. Results At a median follow-up period of 20 months (range 6-38), four patients showed evidence of local recurrence at a rate of 36.4% (4/11). Median overall survival was 20 months. The overall survival rates at one, two, and three years after MWA were 88.7%, 63.6%, and 42.3%, respectively. Complications after MWA included pneumothorax (33.3%), hemoptysis (33.3%), intrapulmonary bleeding (25%), pleural effusion (16.7%), and pulmonary infection (8.3%). None of the patients died during the procedure or in the 30 days after MWA. Conclusion CT-guided percutaneous MWA is safe and effective for the treatment of peripheral NSCLC in patients with a single lung after prior pneumonectomy.

Enteral nutrition feeding in Chinese intensive care units: a cross-sectional study involving 116 hospitals.

Abstract: There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2–19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2–3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353–0.599; p < 0.001). AGI 4 was significantly associated with lower hazard of EN administration (HR 0.056; 95% CI 0.008–0.398; p = 0.004). In a linear regression model, greater Sequential Organ Failure Assessment scores (coefficient – 0.002, 95% CI – 0.008 to − 0.001; p = 0.024) and male gender (coefficient – 0.144, 95% CI – 0.203 to − 0.085; p < 0.001) were found to be associated with lower EN proportion. As compared with AGI 1, AGI 2–3 was associated with lower EN proportion (coefficient – 0.206, 95% CI – 0.273 to − 0.139; p < 0.001). The study showed that EN delivery was suboptimal in Chinese ICUs. More attention should be paid to EN use in the early days after ICU admission.

Clinicopathological features and survival of early stage breast cancer in northwest China: A population-based retrospective study of 1287 patients.

Abstract: Background Breast cancer (BC) displays different clinicopathological features and outcomes based on patient age, molecular subtype, and treatment. However, such features in BC patients in northwest China are unclear. This study investigated the clinicopathological features and overall survival (OS) of early stage BC patients using a population-based study. Methods Patients who were newly diagnosed with BC at the First Affiliated Hospital of Xi'an Jiaotong University between January 2001 and June 2012 were included. Clinicopathological features and OS were assessed. Results The median age of 1287 patients was 50 years, with an average tumor size of 2.65 cm. Additionally, 42.7% were luminal A, 25.6% luminal B, 9.3% Her2 overexpression, and 17.7% triple negative. The cut-off age was 35 years, and young patients (< 35) tended to have larger tumors, ≥ 4 positive lymph nodes, grade 2 or 3 histology, non-luminal types, high Ki67, and poor outcomes. Patients with luminal A tumors showed moderate features: 50.6% had tumors < 2 cm, 56.7% had negative lymph nodes. Patients with Her2 overexpression tumors showed aggressive features and the poorest survival (5-year OS 67.6%). Patients with triple negative tumors were the youngest (average 48.4 years), but had the largest proportion of grade 3 histology and poor outcomes. Conclusion Our results are consistent with those in other provinces in China, but showed an earlier age at diagnosis and more aggressive pathological features compared to developed countries. Additionally, each molecular subtype showed specific features and different survival outcomes.

VCAM1-targeted RNA interference inhibits the proliferation of human oral squamous carcinoma HN12 cells.

Abstract: In the present study, RNA interference (RNAi) was used to investigate the effect of vascular cell adhesion molecule 1 (VCAM1) silencing on the proliferation of human oral squamous carcinoma HN12 cells. HN12 cells were divided into three groups: The untreated blank control cell group (CK), the negative control group transfected with non-homologous vector (NC) and the positive group transfected with the target sequence VCAM1 small hairpin RNA (KD). Reverse-transcription polymerase chain reaction and western blot analysis were used to examine the effects of VCAM1-knockdown on the mRNA expression of VCAM1 and subsequent protein expression. Furthermore, the HN12 cell growth inhibition rate was detected using the cell counting kit-8 method. The VCAM1-targeted lentiviral vector RNAi significantly inhibited VCAM1 mRNA, and subsequent protein, expression. Compared with the NC group, the VCAM1 gene knockdown efficiency was ~85%, while the expression level of VCAM1 protein was reduced by ~74% in KD group cells. In addition, cell growth was significantly inhibited in the KD group, with a growth inhibition rate of ~34%. Therefore, this targeted lentiviral vector RNAi effectively inhibited VCAM1 gene, and subsequent protein, expression, as well as the proliferation of oral squamous carcinoma cells. These results may provide an experimental reference for the diagnosis and treatment of oral squamous cell carcinoma.

Effects of recombinant human growth hormone on protein malnutrition and IGF-1 and IL-2 gene expression levels in chronic nephrotic syndrome.

Abstract: The aim of the study was to investigate the effects of recombinant human growth hormone on protein malnutrition and insulin-like growth factor-1 (IGF-1) and interleukin-2 (IL-2) gene expressions in chronic nephrotic syndrome. Eighty patients with chronic nephrotic syndrome were admitted to our hospital. The patients were included in the study period from January 2015 to December 2016 and were divided into two groups (40 cases in each group) according to the random number method. All the patients enrolled received symptomatic and supportive treatment. The observation group was injected subcutaneously with recombinant human growth hormone, while the control group was treated with Shenyankangfu tablets. The recovery time of the clinical symptoms, change in serum protein, caloric intake and protein metabolism after intervention were compared between the two groups. Changes in serum cystatin C, IGF-1 and IL-2 before intervention, and at 1 week, 1 month and 3 months after intervention were detected, and the adverse reactions in the two groups were observed during the treatment. After intervention, the improvement time of proteinuria, hypoproteinemia, edema and hyperlipidemia in the observation group was significantly shorter than that in the control group (P<0.05). The expression of transferrin, pre-albumin, albumin and total protein in the observation group was significantly superior increased compared to those in the observation group prior to intervention and the control group after intervention (P<0.05). In addition the caloric intake, protein intake and urea nitrogen survival rate in the observation group were significantly superior to those in the observation group prior to intervention and the control group after intervention (P<0.05). At 1 week, 1 month and 3 months after intervention, the levels of serum cystatin C, IGF-1 and IL-2 in the observation group were markedly obviously lower than those in the control group during the same period (P<0.05). The total proportion of allergy, systemic pruritus, nausea and vomiting, abdominal distension and abdominal pain in the observation group was obviously lower than that in the control group (P<0.05). Compared with the traditional Chinese medicine Shenyankangfu tablets applied in the control group, the recombinant human growth hormone used for patients with chronic nephrotic syndrome can improve the clinical symptoms more quickly, regulate the protein metabolism and reduce the inflammatory response in the body, which also has fewer adverse reactions and higher safety.

Microhemorrhage identified on 3.0 T MR susceptibility-weighted imaging for prognosis of viral encephalitis.

Abstract: OBJECTIVE To evaluate the relationship of microhemorrhage on susceptibility-weighted imaging (SWI) with the severity of clinical symptoms and the prognosis of viral encephalitis. MATERIALS AND METHODS Thirty patients with clinically diagnosed viral encephalitis were divided into three groups according to the Glasgow Coma Scale (GCS) and the condition of recovery namely, Group I (n = 12): Glasgow Coma Scale (GCS)≥13 and recovered with no sequelae; Group II (n = 11): GCS 9-12 and recovered with some sequelae; Group III (n = 7): GCS 3-8 and recovered with more severe sequelae. The microhemorrhage detectability on SWI and conventional MR imaging in these three groups was compared and their correlations with different seriousness of clinical symptoms and prognosis were analyzed. RESULTS There was a significant difference in microhemorrhage volume among different MR sequences (p < 0.05). SWI was more sensitive to detect microhemorrhage than conventional MR imaging techniques. Microhemorrhages on SWI were significantly different among the three groups (p < 0.01). The volume of microhemorrhage on SWI was well correlated with the degree of clinical symptoms and the prognosis of viral encephalitis. CONCLUSION SWI can be used to detect microhemorrhage in patients with viral encephalitis. Assessment of microhemorrhage with SWI can provide useful information for the prognosis evaluation of viral encephalitis.

Retraction Note to: Differences in the expression profiles of claudin proteins in human nasopharyngeal carcinoma compared with non-neoplastic mucosa.

Abstract: The editor has retracted this article [1] because of flaws and inconsistencies in the methodology, reporting and interpretation of the data.

[Effects of mild hypothermia on β-adrenergic signaling pathway in a cardiac arrest swine model].

Abstract: Objective To observe the effect of mild hypothermia on myocardial β-adrenergic receptor (β-AR) signal pathway after cardiopulmonary resuscitation (CPR) in pigs with cardiac arrest (CA) and explore the mechanism of myocardial protection. Methods Healthy male Landraces were collected for reproducing the CA-CPR model (after 8-minute untreated ventricular fibrillation, CPR was implemented). The animals were divided into two groups according to random number table (n = 8). In the mild hypothermia group, the blood temperature of the animals was induced to 33 ℃ and maintained for 6 hours within 20 minutes after return of spontaneous circulation (ROSC) by using a hypothermia therapeutic apparatus. In the control group, the body temperature of the animals was maintained at (38.0±0.5)℃ with cold and warm blankets. The heart rate (HR), mean arterial pressure (MAP), the maximum rate of increase or decrease in left rentricular pressure (+dp/dt max) were measured during the course of the experiment. The cardiac output (CO) was measured by heat dilution methods before CA (baseline), and 0.5, 1, 3, 6 hours after ROSC respectively, the venous blood was collected to detect the concentration of cTnI. Left ventricular ejection fraction (LVEF) was measured with cardiac ultrasound before CA and 6 hours after ROSC. Animals were sacrificed at 6 hours after ROSC and the myocardial tissue was harvested quickly, the mRNA expression of β1-AR in myocardium was detected by reverse transcription-polymerase chain reaction (RT-PCR), the contents of adenylate cyclase (AC) and cyclic adenosine monophosphate (cAMP) were detected by enzyme linked immunosorbent assay (ELISA), the protein content of G protein-coupled receptor kinase 2 (GRK2) was detected by Western Blot. Results After successful resuscitation, the HR of both groups were significantly higher than the baseline values, CO, ±dp/dt max were significantly decreased, MAP were not significantly changed, serum cTnI levels were significantly increased. Compared with the control group, HR at 0.5, 1, 3 hours after ROSC were significantly decreased in mild hypothermia group (bpm: 142.80±12.83 vs. 176.88±15.14, 115.80±11.48 vs. 147.88±18.53, 112.60±7.40 vs. 138.50±12.02, all P < 0.01), CO was significantly increased at 1 hours and 3 hours after ROSC (L/min: 3.97±0.40 vs. 3.02±0.32, 4.00±0.11 vs. 3.11±0.59, both P < 0.01), +dp/dt max at 3 hours and 6 hours was also significantly increased after ROSC [+dp/dt max (mmHg/s): 3 402.5±612.7 vs. 2 130.0±450.6, 3 857.5±510.4 vs. 2 562.5±633.9; -dp/dt max (mmHg/s): 2 935.0±753.2 vs. 1 732.5±513.6, 3 520.0±563.6 vs. 2 510.0±554.3, all P < 0.05], the cTnI was significantly decreased at 3 hours and 6 hours afher ROSC (μg/L: 1.39±0.40 vs. 3.24±0.78, 1.46±0.35 vs. 3.78±0.93, both P < 0.01). The left at 6 hours after ROSC in both groups was decreased as compared with that before CA. The LVEF in the mild hypothermia group was higher than that in the control group (0.52±0.04 vs. 0.40±0.05, P < 0.05). The mRNA expression of β1-AR, and concentrations of AC and cAMP in hypothermia group were significantly higher than those in control group [β1-AR mRNA (2-ΔΔCT): 1.18±0.39 vs. 0.55±0.17, AC (ng/L): 197.0±10.5 vs. 162.0±6.3, cAMP (nmol/L): 1 310.58±48.82 vs. 891.25±64.95, all P < 0.05], GRK2 was lower than that in the control group (GRK2/GAPDH: 0.45±0.05 vs. 0.80±0.08, P < 0.05). Conclusion Mild hypothermia can reduce the degree of cardiac function injury after CPR, and its mechanism may be related to the reduction of impaired myocardial β-AR signaling after CPR. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Mild hypothermia; β-adrenergic signaling pathway

Differences in the expression profiles of claudin proteins in human nasopharyngeal carcinoma compared with non-neoplastic mucosa.

Abstract: Background Several studies have suggested that claudin proteins, which are the main components of tight junction structures, are related to the regulation of cell polarity and cell differentiation. Method To explore the expression profiles of the tight junction proteins claudin-2, - 5, - 8 and - 9 in nasopharyngeal carcinoma, IHC (immunohistochemical analysis), Western blot and real-time PCR were used to detect the expression profiles of these claudin proteins in nasopharyngeal carcinoma tissues and in non-neoplastic mucosal tissues. Results According to our study, the expression levels of claudin-2 and claudin-5 were reduced, while the expression of claudin-8 was increased in nasopharyngeal carcinoma tissues in comparison with non-neoplastic mucosal tissues. Correlations between claudin-2 and -5 expression and metastatic progression in nasopharyngeal carcinoma patients were also found. Conclusion In summary, our research reveals distinct expression profiles of claudin-2, - 5 and - 8 in non-neoplastic mucosal tissues and nasopharyngeal carcinoma tissues. In addition, the expression of these claudin proteins was highly correlated with metastatic progression and prognosis in patients with nasopharyngeal carcinoma and had predictive value for the metastasis and survival of nasopharyngeal carcinoma patients.