Jia Wang

The IL-28B rs12979860 CC and rs8099917 TT genotypes were proved to be predictor for pegylated-interferon (PEG-IFN)/ribavirin (RBV)-treated hepatitis C virus (HCV) patients. However, there were no identical conclusions on rs12980275 polymorphism. Our aim is to perform a meta-analysis in order to determine the association between rs12980275 polymorphism of IL28B and the sustain viral response (SVR) of HCV patients with PEG-IFN/RBV therapy. Studies were retrieved from PubMed and Chinese China National Knowledge Infrastructure (CNKI). Data were extracted by two investigators and analyzed using Stata 11.0 software. Sixteen articles, containing 19 independent studies were included in the analysis. The results showed that patients with AA genotype of rs12980275 achieved higher SVR than patients with AG/GG genotypes. The overall OR (95% CI) was 3.118 (2.146, 4.529). In subgroup analysis by ethnicity, the ORs (95% CIs) were 3.084 (1.454, 6.542) and 2.736 (1.863, 4.018) in Asian and Caucasian population, respectively. Another subgroup analysis by HCV genotype, the ORs (95% CIs) were 3.976 (2.568, 6.158), 1.462 (0.504, 4.240) and 1.489 (0.916, 2.421) in patients with HCV genotype 1/4, mix genotype, and HCV genotype 2/3, respectively. AA genotype of rs12980275 was a predictive factor for SVR in HCV patients with PEG-IFN/RBV treatment, especially in HCV genotype 1/4.

Since 2013 the occurrence of human infections by a novel avian H7N9 influenza virus in China has demonstrated the continuing threat posed by zoonotic pathogens. Although the first outbreak wave that was centred on eastern China was seemingly averted, human infections recurred in October 2013 (refs 3, 4, 5, 6, 7). It is unclear how the H7N9 virus re-emerged and how it will develop further; potentially it may become a long-term threat to public health. Here we show that H7N9 viruses have spread from eastern to southern China and become persistent in chickens, which has led to the establishment of multiple regionally distinct lineages with different reassortant genotypes. Repeated introductions of viruses from Zhejiang to other provinces and the presence of H7N9 viruses at live poultry markets have fuelled the recurrence of human infections. This rapid expansion of the geographical distribution and genetic diversity of the H7N9 viruses poses a direct challenge to current disease control systems. Our results also suggest that H7N9 viruses have become enzootic in China and may spread beyond the region, following the pattern previously observed with H5N1 and H9N2 influenza viruses.

To study the effect of hypoxia on the proliferation of hBMSCs and human placental decidua basalis-MSCs (hPDB-MSCs), and to provide the theoretical basis for discovering the new seed cells source for tissue engineering. Density gradient centrifugation method was adopted to isolate and culture hBMSCs and hPDB-MSCs, flow cytometry (FCM) was applied to detect cell surface marker. After establishing the experimental model of CoCl2 chemical hypoxia, MTT method was applied to evaluate the proliferation of hBMSCs and hPDB-MSCs at different time points (6, 12, 24, 48, 72, 96 hours) with various CoCl2 concentration (0, 50, 75, 100, 125, 150, 175, 200 micromol/L). FCM analysis revealed that hPDB-MSCs and hBMSCs expressed CD9, CD29, CD44, CD105, CD106 and human leucocyte antigen ABC (HLA-ABC), but both were absent for CD34, CD40L and HLA-DR. Compared with hBMSCs, hPDB-MSCs expressed stage-specific embryonic antigen 1 (SSEA-1), SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81 better. The proliferations of hPDB-MSCs and hBMSCs were inhibited within the first 12 hours under hypoxia condition, but promoted after 12 hours of hypoxia. Compared with the control group, the hBMSCs were remarkably proliferated 24 hours after hypoxia with CoCl2 concentration of 150 micromol/L (P < 0.05), while hPDB-MSCs were significantly proliferated 12 hours after hypoxia with CoCl2 concentration of 75 micromol/L (P < 0.05). Compared with hBMSCs, hPDB-MSCs express more specific surface antigens of embryonic stem cells and are more sensitive to the proliferation effects of chemical hypoxia, indicating it may be a new seed cells source for tissue engineering.

Adenovirus E4 promoter-binding protein 4 (E4BP4), a mammalian basic leucine zipper (bZIP) nuclear transcription factor, was identified to be involved in cell survival and proliferation. Previous research data showed that the expression of E4BP4 gene was up-regulated at the implantation sites on day 5 pregnancy of mouse. The aim of the present study was to examine the expression pattern of E4BP4 gene in uterus during pre-implantation period, and at the implantation sites and inter-implantation sites during the implantation process, through the Northern blot, in situ hybridization, Western blot and immunohistochemistry analyses. It was found that, (1) during the pre-implantation period, the expression of E4BP4 gene was gradually increased; (2) its expression was sharply up-regulated at the implantation sites compared with that at the inter-implantation sites during the embryo implantation process; (3) the uterine expression of E4BP4 gene was not embryo-dependent, but observed in artificially induced decidulization of pseudopregnant mouse; (4) both E4BP4 mRNA and E4BP4 protein were localized in stromal cells and decidual cells around the uterine lumen. These results indicated that E4BP4 may play a critical role in embryo implantation process by promoting stromal cell proliferation and inhibiting decidual cell apoptosis.

We have examined morphological change and movements of individual sunspots within a sunspot group in association with a large solar flare activity (3B/X1.5) appeared on 13 May 1981. For this purpose we measured distance among spots during the period before and after the flare activity and estimated the average velocity of their movement. Our main results are as follows: (1) The longitudinal displacement among sunspots are generally greater than the latitudinal displacement. (2) During the period the spots moved with an average velocity of 1.2 km/s in longitude and 0.86 km/s in latitude. (3) The most notable change took place in the central part placed between the two ribbons of the flare.

A 12-pole wideband high-temperature superconducting (HTS) microstrip bandpass filter is reported in this paper. The filter has a center frequency of 23 GHz and a bandwidth of 4.2 GHz. The filter was fabricated on a 2-in-diameter 0.25-mm-thick MgO wafer with double-sided YBCO films. Both edge and end coupling structures were employed in this paper to achieve the desired bandwidth. An insert coupling structure was used for input/output coupling to realize the remarkably strong coupling. A microwave-absorbing material was used to eliminate cavity resonances. The measured results show a midband insertion loss of 1.3 dB, a return loss better than 9.5 dB and an out-of-band rejection of over 55 dB on both sides of the passband.

Drug-induced liver injury (DILI) is a frequent cause of pediatric liver disease; however, the data on DILI are remarkably limited. All 69 children hospitalized with DILI between January 2009 and December 2011 were retrospectively studied. A total of 37.7% of the children had medical histories of respiratory infection. The clinical injury patterns were as follows hepatocellular 89.9%, cholestatic 2.9%, and mixed 7.2%. Liver biopsies from 55 children most frequently demonstrated chronic (47.3%) and acute (27.3%) hepatitis. Hypersensitivity features, namely, fever (31.9%), rash (21.7%), and eosinophilia (1.4%), were found. Twenty-four children (34.8%) developed chronic DILI. Antibiotics (26.1%) were the most common Western medicines (WMs) causing DILI, and the major implicated herbs were Ephedra sinica and Polygonum multiflorum. Compared with WM, the children whose injuries were caused by Chinese herbal medicine (CHM) showed a higher level of total bilirubin (1.4 mg/dL vs 16.6 mg/dL, p=0.004) and a longer prothrombin time (11.8 seconds vs 17.3 seconds, p=0.012), but they exhibited less chronic DILI (2/15 vs 18/39, p=0.031). Most cases of DILI in children are caused by antibiotics or CHM used to treat respiratory infection and present with hepatocellular injury. Compared with WM, CHM is more likely to cause severe liver injury, but liver injury caused by CHM is curable.

Dysfunction of central and skin Hypothalamic-Pituitary-Adrenal (HPA) axis play important roles in pathogenesis of atopic dermatitis (AD). Our previous studies showed that several Chinese herbs could improve HPA axis function. In this study, we evaluated the anti-inflammatory effects of BuShenYiQi granule (BSYQ), a Chinese herbs formula, in AD mice and explored the effective mechanism from regulation of HPA axis. The ovalbumin (OVA) induced AD mice model were established and treated with BSYQ. We evaluated dermatitis score and histology analysis of dorsal skin lesions, meanwhile, serum corticosterone (CORT), adrenocorticotropic hormone (ACTH), corticotropin-releasing hormone (CRH) and inflammatory cytokines were determined by ELISA. The changes of CRH/proopiomelanocortin(POMC) axis elements, corresponding functional receptors and crucial genes of glucocorticosteroidogenesis in the skin were measured by quantitative real-time PCR and western blot, respectively. The symptoms and pathological changes in skin of AD mice were significantly improved and several markers of inflammation and allergy descended obviously after BSYQ treatment. We found that AD mice had insufficient central HPA tone, but these conditions were markedly improved after BSYQ treatment. The AD mice also showed a disturbed expression of skin HPA. In lesion skin of AD mice, the mRNA and protein expressions of CRH decreased significantly, on the contrary, POMC and cytochrome P450 side-chain cleavage enzyme (CYP11A1) increased markedly, meanwhile, NR3C1 (mouse GR), CRHR2 and 11-hydroxylase type 1(CYP11B1) were reduced locally. Most of these tested indexes were improved after BSYQ treatment. AD mice displayed the differential expression pattern of central and skin HPA axis and BSYQ treatment significantly alleviated the symptoms of AD mice and presented anti-inflammatory and anti-allergic effects via regulating the expression of central and skin HPA axis.

The demand for effective intervention for subhealth conditions is growing with increasing numbers of people being in a state of subhealth with a poor quality of life. Future research and evaluation of the treatment methods for subhealth conditions from the perspective of traditional Chinese medicine (TCM) may provide an important direction for developing effective management of these conditions. To evaluate the efficacy and safety of Xiaopi Yishen herbal extract granules (XPYS-HEG), a compound traditional Chinese herbal medicine for relieving fatigue and promoting a cheerful spirit for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency. DESIGN, SETTING PARTICIPANTS AND INTERVENTIONS: A multi-center, randomized, double-blinded, placebo-controlled clinical study was undertaken. The study period was 18 weeks, including 6 weeks for intervention and 12 weeks for follow-up. Participants were recruited from medical center and outpatient clinics of three hospitals in China, i.e. Xiaotangshan Hospital of Beijing, the First Affiliated Hospital of Henan University of TCM and the Affiliated Hospital of Liaoning University of TCM. Two hundred participants who met the criteria of fatigue-predominant subhealth and liver-qi stagnation and spleen-qi deficiency in TCM were allocated randomly to the treatment group (XPYS, n=100) and control group (placebo, n=100). The total score of Fatigue Scale-14 (FS-14) was used to evaluate the fatigue status of subjects and the extent of liver-qi stagnation and spleen-qi deficiency syndrome was also recorded. Three cases in the XPYS group withdrew from the trial. There were 200 subjects who entered to full analysis set (FAS) analysis and 197 subjects fitted in the per-protocol set (PPS) analysis. (1) According to the score changes of FS-14, the effectiveness rates in the XPYS and placebo group were as follows: 14.0% vs 9.0% (FAS) and 14.4% vs 9.0% (PPS) for complete remission, 19.0% vs 15.0% (FAS) and 19.6% vs 15.0% (PPS) for obvious effects, 39.0% vs 26.0% (FAS) and 39.2% vs 26.0% (PPS) for effective, and 72.0% vs 50.0% (FAS) and 73.2% vs 50.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to the placebo statistically (P<0.05). (2) According to the score changes of TCM syndrome, the effectiveness rates in the XPYS group and placebo group were as follows: 1.0% vs 0.0% (FAS) and 1.0% vs 0.0% (PPS) for complete remission, 20.0% vs 7.0% (FAS) and 19.6% vs 7.0% (PPS) for obvious effects, 29.0% vs 24.0% (FAS) and 29.9% vs 24.0% (PPS) for effective, and 50.0% vs 31.0% (FAS) and 50.5% vs 31.0% (PPS) for complete efficacy. The efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (3) The follow-up results at 12 weeks and 18 weeks showed that the efficacy of XPYS-HEG was superior to that of placebo statistically (P<0.05). (4) No adverse effects were found in the XPYS group. It can be concluded that XPYS-HEG is effective and safe for the treatment of people with fatigue-predominant subhealth due to liver-qi stagnation and spleen-qi deficiency.

The plant mitochondrial electron transport chain (ETC) includes a non-energy conserving alternative oxidase (AOX) thought to dampen reactive oxygen species (ROS) generation by the ETC and/or facilitate carbon metabolism by uncoupling it from ATP turnover. When wild-type (WT) Nicotiana tabacum grown at 28°C/22°C (light/dark) were transferred to 12°C/5°C, they showed a large induction of leaf Aox1a mRNA and AOX protein within 24 h. Transfer to cold also resulted in a large accumulation of monosaccharides, an increase in transcript level of genes encoding important ROS-scavenging enzymes and a moderate increase in lipid peroxidation. Transgenic plants with suppressed AOX level showed less cold-induced sugar accumulation than WT while transgenic plants with enhanced AOX levels showed enhanced sugar accumulation. This is inconsistent with the hypothesis that AOX acts to burn excess carbohydrate, but rather suggests a role for AOX to aid sugar accumulation, at least during cold stress. At 28°C/22°C, plants with suppressed AOX had elevated levels of lipid peroxidation compared with WT, while plants with enhanced AOX had reduced lipid peroxidation. This is consistent with the hypothesis that AOX dampens ROS generation and oxidative damage. However, this inverse relationship between AOX level and lipid peroxidation did not hold upon shift to cold. Under this stress condition, plants with strong suppression of AOX show enhanced induction of ROS-scavenging enzymes compared with WT and decline in lipid peroxidation. These data suggest that, under stress conditions, the lack of AOX enhances a mitochondrial stress-signaling pathway able to increase the ROS-scavenging capacity of the cell.

CXC chemokine receptor 4 (CXCR4) was considered to be an important factor in cancer cell metastasis. This study was aimed to examine the expression of CXCR4 in ovarian cancer and determine the functions and the possible mechanisms of CXCR4 in the progression of ovarian cancer. CXC chemokine receptor 4 messenger RNA expression in normal ovarian tissues, malignant epithelial ovarian tumors, and 3 ovarian cancer cell lines was analyzed. Immunohistochemical analysis was used to detect the protein expression of CXCR4 and β-catenin in normal and malignant ovarian tissues. The effect of CXCR4 inhibition on cell proliferation and invasion was determined. CXC chemokine receptor 4 was highly expressed in malignant ovarian tumors and ovarian cancer cell lines, and the different expression of CXCR4 was observed between the ovarian cancers with lymph node metastasis and without lymph node metastasis. Furthermore, The CXCR4 expression was correlated with β-catenin expression in ovarian tissues. Moreover, knockdown of CXCR4 could obviously reduce proliferation and invasion of ovarian cancer cell and inhibit Wnt target genes and mesenchymal markers such as vimentin and SLUG expression. CXC chemokine receptor 4 plays a critical role in the metastasis of human ovarian cancer possibly through modulating the Wnt/β-catenin pathway. CXC chemokine receptor 4 is a potential therapeutic target for treatment of ovarian cancer.

To study the chemical constituents of Ligusticum sinense. The chemical constituents were isolated and purified by column chromatography on silica gel and Sephadex LH-20; Using spectroscopy methods to elucidate their structures. Nine compounds were isolated and identified as levistolide A (1), (Z)-3-butylidene-7-hydroxyphthalide (2), senkyunolide B (3), 3-butylphthalide(4), (Z)-ligustilide (5), riligustilide (6), neocnidilide (7), senkyunolide A (8), beta-sitostesol (9). Compounds 2 and 3 are obtained from this plant for the first time.

We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. All the lesions were located in the cortex and their mean size was 1.3 ± 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions.

PI3K is a promising therapeutic target for cancer. With PI-103 as the lead compound, we designed and synthesized 4-(2-arylpyrido[3',2':3,4]pyrrolo[1,2-f][1,2,4]triazin-4-yl)morpholine derivatives. 9, 10a, 10d, 10e had the IC(50) against PI3Kα comparable with PI-103. All of the compounds showed selectivity over 15 tested protein kinases and anti-proliferative activity at micromolar concentration against several cancer cell lines.

To compare the dose and image quality of three methods for reducing the radiation dose to the eye at head computed tomography (CT): bismuth shielding, organ-based tube current modulation (TCM), and global reduction of the tube current. An anthropomorphic head phantom was scanned under six conditions: (a) without any dose reduction techniques (reference scanning); (b) with one bismuth eye shield; (c) with organ-based TCM; (d) with reduced tube current to yield the same dose reduction as one bismuth shield; (e) with two layers of bismuth shields; and (f) with organ-based TCM and one bismuth shield. Dose to the eye, image noise, and CT numbers in the brain region were measured and compared. The effect of increasing distance between the bismuth shield and eye lens was also investigated. Relative to the reference scan, the dose to the eye was reduced by 26.4% with one bismuth shield, 30.4% with organ-based TCM, and 30.2% with a global reduction in tube current. A combination of organ-based TCM with one bismuth shield reduced the dose by 47.0%. Image noise in the brain region was slightly increased for all dose reduction methods. CT numbers were increased whenever the bismuth shield was used. Increasing the distance between the bismuth shield and the eye lens helped reduce CT number errors, but the increase in noise remained. Organ-based TCM provided superior image quality to that with bismuth shielding while similarly reducing dose to the eye. Simply reducing tube current globally by about 30% provides the same dose reduction to the eye as bismuth shielding; however, CT number accuracy is maintained and dose is reduced to all parts of the head.

MicroRNAs (miRNAs) are important regulators of cell fate decisions, while the miRNAs and their targets in the regulation of stem cell differentiation are largely unidentified. Here we report novel functions of miR-125b/Lin28 axis in the regulation of mouse embryonic stem cell (mESC) lineage specification and cardiomyocyte differentiation. With a MicroRNA Array screen, we identified a number of miRNAs significantly changed during ESC differentiation, among which miR-125b showed a marked reduction during early differentiation. The abundantly expressed miR-125b in undifferentiated mESCs was dramatically downregulated to a level hardly detected during differentiation day 3 to 5, with a concomitant upregulation of Lin28. Ectopically expressing miR-125b did not alter characteristics of undifferentiated mESCs, whereas it impaired the endoderm and mesoderm development, but not the ectoderm, and inhibited cardiomyocyte formation. We further demonstrate that miR-125b targeted the 3'-untranslated region of Lin28 and reduced the abundance of Lin28 at both mRNA and protein levels. Moreover, phenotypes of miR-125b overexpressing cells were mimicked by downregulation of Lin28 and rescued by reintroduction of Lin28. In addition, the impaired cardiogenesis in miR-125b-introduced cells was greatly recovered when mimicking endoderm environment by cultivation with the condition medium from a visceral endoderm-like cell line, END-2. These results reveal that the miR-125b/Lin28 axis is an important regulator of early lineage specification and cardiomyocyte differentiation of ESCs.

To explore the magnetic resonance imaging (MRI) manifestations of pancreatic neuroendocrine carcinoma (PNC). The clinical data of 7 PNC patients as confirmed by pathological examination were analyzed retrospectively and the relevant literatures discussed. Among them, 2 patients were misdiagnosed for benign tumor lesion, one for SPT and another for pancreatic cancer with liver metastasis. And 3 were diagnosed correctly. The lesions showed irregular or lobulated shapes: 5 in body and tail of pancreas and 2 in head of pancreas. All lesions were hypointense on T(1)WI. They were iso- to slightly hyperintense (n = 5) and heterogeneously hyperintense (n = 2) on T(2)WI. Dynamic contrast-enhanced MRI was performed in all. There were slight enhancement (n = 2) and moderate enhancement (n = 5) during arterial phase. During interstitial and delayed phases, there were gradual enhancement (n = 2) and less enhancement (n = 5) than pancreatic parenchyma. There were metastasis of lymph nodes (n = 1), splenic metastasis (n = 2), liver metastasis (n = 1) and invasion of pancreatic capsule (n = 3). Due to the lack of MRI specificities, a definite diagnosis of pancreatic neuroendocrine carcinoma must be made by pathological examination and immunohistochemistry.

We investigated the value of intraoperative sonography in improving the prevalence of total tumor resection and the survival time of patients who underwent resection of cerebral gliomas. One hundred thirty-seven patients who underwent sonographically guided surgery were followed for 6 to 60 months. In addition, 60 randomly selected patients (30 with low-grade gliomas and 30 with high-grade gliomas) who had surgery in our hospital without sonographic guidance served as the control group. Follow-up included the survival time, and the difference in the survival time between the study and control groups was statistically analyzed. Total removal of the lesion was achieved in 77 cases (69%), and partial removal was achieved in 35 (31%). In the control low-grade glioma group, 6-month survival was 96.7%; 1-year survival was 73.3%; and 2-year survival was 53.3%. In the study low-grade glioma group, survival rates at 6 months, 1 year, and 2 years were 98.0%, 96.1%, and 88.2%, respectively. In the control and study high-grade glioma groups, survival rates at 6 months, 1 year, and 2 years were 83.3% and 93.4%, 43.3% and 59.2%, and 13.3% and 32.8%. When comparing survival at 6 months, 1 year, and 2 years between the control and study groups, there was no significant difference at 6 months (P > .05), but survival at 1 and 2 years was significantly different (P < .05). Sonographically guided resection of cerebral gliomas helps the surgeon understand the relationship between the lesion and the surrounding structures. It is of value in improving the prevalence of total tumor resection and the patient's survival time.

Egg white protein powder was hydrolyzed with Alcalase to produce antioxidant peptides. Then, the peptides were fractionated with ultrafiltration membranes. The peptides (1-10 kDa) were further treated by pulsed electric field (PEF) to investigate its effect on the antioxidant activity of the peptides. Antioxidant activity was evaluated using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition assay. The results indicated that optimal electric field intensity and standing times of PEF can enhance the antioxidant activity of the peptides. Therefore, a Box-Behnken design (BBD) with three independent variables including concentration, electric field intensity and pulse frequency was used to establish the regression equation of second-order response surface. The optimal conditions were as follows: concentration 8 mg/ml, electric field intensity 10 kV/cm and pulse frequency 2400 Hz. Under these conditions, the peptides antioxidant activity was 62.64% ± 0.98%. The present study demonstrated that the antioxidant activity of peptides (1-10 kDa) could be improved using PEF.

Ginseng acidic polysaccharide WGPA isolated from the root of Panax ginseng C. A. Meyer was fractionated into WGPA-A and WGPA-N by anion-exchange chromatography. The antifatigue activity of ginseng acidic polysaccharide WGPA has been reported in our previous research. This present study was designed to identify its active component and elucidate the mechanism for preventing chronic fatigue syndrome (CFS). WGPA, WGPA-A and WGPA-N were orally administered to mice once daily for 15 days. The effects of these compounds on physiological biomarkers of oxidative stress and on the morphology of the mitochondria in striated skeletal muscle were assessed. The results of forced swimming test-induced indicated that WGPA and WGPA-A could lengthen the swimming time, while WGPA-N could not. In addition, malondialdehyde and lactate dehydrogenase levels in serum were enhanced; while those of superoxide dismutase and glutathione peroxidase were lowered. Interestingly, the structural degeneration of mitochondria were all ameliorated. These findings suggested that WGPA-A is the active component of WGPA, it might have potential therapeutic effects for CFS and the oxidative stress might be involved in the pathogenesis. Our results also provided essential data for a better understanding of the antifatigue effects of P. ginseng extracts.

In this study, we demonstrate that killer cell lectin-like receptor subfamily G member 1 (KLRG1), a transmembrane protein preferentially expressed on T cells, is highly expressed on CD56(+) NK cells, which are significantly reduced in their numbers and functions in the peripheral blood of patients with chronic hepatitis C virus (HCV) infection compared to subjects without infection. KLRG1 expression is also upregulated on healthy NK cells exposed to Huh-7 hepatocytes infected with HCV in vitro. Importantly, the expression levels of KLRG1 are inversely associated with the capacity of NK cells to proliferate and to produce gamma interferon (IFN-γ) but positively associated with apoptosis of NK cells in response to inflammatory cytokine stimulation. KLRG1(+) NK cells, including CD56(bright) and CD56(dim) subsets, exhibit impaired cell activation and IFN-γ production but increased apoptosis compared to KLRG1(-) NK cells, particularly in HCV-infected individuals. Importantly, blockade of KLRG1 signaling significantly recovered the impaired IFN-γ production by NK cells from HCV-infected subjects. Blockade of KLRG1 also enhanced the impaired phosphorylation of Akt (Ser473) in NK cells from HCV-infected subjects. Taken together, these results indicate that KLRG1 negatively regulates NK cell numbers and functions via the Akt pathway, thus providing a novel marker and therapeutic target for HCV infection.

To compare the prognoses of non-small cell lung cancer patients based respectively on the 6th-Edition Staging System for NSCLC (the 6th-Edition Staging System) and the new staging system by the International Association for the Study of Lung Cancer (IASLC) (new staging system). Data were collected from 136 operated NSCLC patients from Sep. 2003 through Oct. 2007. Those data were staged based respectively on the 6th-Edition Staging System and the new staging system. The 2-year no-recurrence survival rate was calculated, and life span was analyzed using the Kaplan-Meier method of SPSS 13.0 software. (1) In this series, using the 6th-Edition Staging System, there were 56, 23, 53 and 4 patients in stage I, stage II, stage III and stage IV respectively; using the new staging system, there were 50, 31, 54 and 1 patients in stage I, stage II, stage III and stage IV respectively. There were 6 patients in stage I according to the 6th-Edition Staging System who had become 6 patients in stage II according to the new staging system, 1 patient in stage II 1 in stage III, 3 patients in stage III 3 in stage II, 1 patient in stage III 1 in stage IV, and 4 patients in stage IV 4 in stage III. (2) According to the 6th-Edition Staging System, the 2-year no-recurrence survival rates for Ia, Ib, IIa, IIb,IIIa, IIIb and IV were 95.0%, 83.3%, 100.0%, 63.6%, 52.1%, 80.0% and 50.0% respectively, and according to the new staging system, the 2-year cumulative survival rates for I a, Ib, IIa, IIb, IIIa, IIIb and IV were 95.5%, 89.3%, 68.4%, 63.6%, 52.8%, 50.0% and 0.0% respectively. After Chi square analysis, there was no distinguished difference between the 2 staging systems for the 2-year cumulative survival rate. (3) According to the 6th-Edition Staging System, the difference between the no-recurrence rate of stage I and stage II was not statistically significant (P = 0.232), and the difference between the no-recurrence rates of stage II and III was statistically significant(P = 0.023); according to the new staging system, the difference between the no-recurrence rates of stage I and stage II as well as between those of stage II and stage III were both statistically significant (P = 0.023 and 0.014 respectively). (4) The differences between the no-recurrence rates of the patients on the two sides, above and below the tumor maximum diameter cutpoint 2 cm, as well as the cutpoint 5 cm were statistically significant (P = 0.025; P = 0.023). The new staging system by NSCLC has better staging specificity than the 6th-Edition Staging System and could be used for Chinese patients.

To verify the correlation between nasal contact point and headache and to discuss the significance of nasal endoscopic surgery through observation of clinical outcomes in patients with nasal mucosa contact point treated by endoscopic surgery. Forty-five patients diagnosed as nasal mucosa contact headache were treated by nasal endoscopic surgery. The results were analyzed retrospectively, including headache degree, headache frequency, lasting time and total time between before and 6, 18, and 24 months after operation. The data were processed by rank-sum test by SPSS 18.0 software. 6, 18 and 24 months after operation, the headache degree (VAS scores were 1.50 [0; 4.00], 2.00 [0; 5.00], 3.25 [0; 5.75], respectively) was relieved (VAS score was 6.00 [5.25; 8.25] before operation) dramatically (Z value were -4.913, -4.070 and -3.095, respectively, all P < 0.01). The total time of headache 6, 18, 24 months after operation (It were 0.07 [0; 3.50], 0.26 [0; 7.77], 1.04[0; 17.15] h, respectively) was shortened (It was 25.20 [4.00; 186.00] h before operation) significantly (Z value were -4.368, -3.652, -2.500, respectively, all P < 0.05). One of the key causes of patients suffered from intractable headaches is mucosal contact in the nasal cavity. The pain in these patients could be relieved through surgical correction of intranasal anatomic abnormalities. Nasal mucosa contact might not be the only etiology of intractable headache since the mechanism of headache is complicated and variable. The effect of endoscopic surgery needs to be estimated by long-term follow-up.

This retrospective study was conducted to evaluate information on paediatric lymphoma in China. We reviewed the pathological files of patients less than 12 years of age with lymphoma in Shanghai Xinhua Hospital from January 1982 to June 2009. SPSS version 11.0 was used to analyse the results. Of the 213 subjects, 176 (82.6%) had non-Hodgkin's lymphoma (NHL) and 37 (17.4%) had Hodgkin's lymphoma (HL). All NHL cases had diffuse and high grade tumours, and 33.5% of these tumours primarily involved extra-nodal sites. Of the NHL cases, 56.6%, 43.3%, and 1.7% were derived from T, B, and null cells, respectively. Lymphoblastic lymphoma (LL, 50.6%), Burkitt's lymphoma (BL, 28.4%), and anaplastic large cell lymphoma (ALCL, 12.5%) comprised the majority of the NHL cases. A significant difference was found in the frequency of stage I/II cases between LL and ALCL. Paediatric HL resembled the disease in adults. Paediatric lymphoma in China is different from that in Western countries with respect to the incidence rate of HL and BL. The distribution pattern of NHL histological subtypes is more similar to that in Japan than that in Pakistan. These features suggest ethnic or geographic variations.

Recurarization has previously been described in the context of acute normovolemic hemodilution. The aim of this study was to investigate the impairment of recovery of neuromuscular function after re-transfusion of intraoperative salvaged blood in patients treated with rocuronium. We enrolled 50 patients undergoing general anesthesia for lumbar surgery. Intraoperative blood salvage (IBS) was used in 30 patients (group I); the remaining 20 comprised a control group (group C). Anesthesia was induced with fentanyl, midazolam, propofol and rocuronium. Rocuronium was infused to maintain neuromuscular blockade during surgery. Blood was collected from the operative field and re-transfused in the post-anesthesia care unit (PACU). Neuromuscular function was monitored using the train-of-four ratio (TOFr). Once the train-of-four ratio exceeded 90 in the PACU, neuromuscular function was evaluated every 5 minutes for 30 minutes. The TOFr and incremental recovery of TOFr from baseline were recorded. Salvaged blood was re-transfused at the beginning of the evaluation for patients in group I, and afterwards for patients in group C. Blood gas analysis was assessed before anesthesia and in the PACU. Incremental recovery of TOFr from baseline was significantly less in group I than controls at 25 minutes (6.1 ± 3.2 vs. 9.1 ± 3.2, respectively; P = 0.001) and 30 minutes (7.1 ± 3.2 vs. 10.0 ± 2.2, respectively; P = 0.001). There were no significant differences in gas exchange between the groups. In patients who had received a rocuronium infusion during anesthesia, re-transfusion of salvaged blood significantly impaired recovery of neuromuscular function recovery in the PACU, but without significant impairment of respiratory function.

The prevalence of allergic asthma has been increased rapidly in recent years. About 20% of all these sufferers have experienced asthma exacerbation. Although corticosteroids and β-agonists therapy improves serious asthma symptoms, they can׳t completely cure these allergic diseases. BuShenYiQi Formula (BSYQF) has been widely used to treat bronchial asthma and its exacerbation for decades in Huashan Hospital of Fudan University, China. Nevertheless, the mechanisms of BSYQF' anti-asthmatic effects haven׳t been fully elucidated. In this study, we evaluated the involvement of Th1, Th2 and Th17 cells in the anti-asthmatic effects of BSYQF in Respiratory Syncytial Virus (RSV)-induced asthma exacerbated mice. BALB/c mice were challenged with ovalbumin (OVA), followed by RSV infections for establishment of asthma exacerbated model. Airway hyperresponsiveness (AHR) was examined by direct airway resistance analysis. Bronchoalveolar lavage fluid (BALF) was assessed for inflammatory cell counts and secreted levels of cytokines. Lung tissues were detected for inflammatory cell infiltration and mucus hypersecretion. Subsequently, CD4(+)T cells and alveolar macrophages were sorted and purified from mice lungs in different groups. CD4(+)T cell subpopulations including the expression levels of important transcription factors in T lymphocyte polarization were examined. In asthma exacerbation group, the purified CD4(+)T cells and macrophages were co-cultured, and the changes of co-cultured cells with BSYQF treatment were further analyzed in vitro. BSYQF significantly attenuated airway hyperresponsiveness and inhibited inflammatory cell infiltration, especially for excessive infiltration of eosinophils and neutrophils. Histopathological analysis showed that BSYQF could suppress airway inflammation and RSV replication. The decreases of antigen-specific IgE, IL-4, IL-5, IL-6, IL-17a and increases of IFN-γ, IL-12 were observed in BALF, lung homogenate or serum after BSYQF treatment. We further confirmed that BSYQF could down-regulate Th2-Th17 cell proportions with lower expressions of GATA3, STAT6 and RORγT, and up-regulate Th1 cell proportion with higher expression of T-bet. And as a result of strengthened Th1-response, activated macrophages were also observed by remarkable enhancement of signature gene expressions and phagocytosis. BSYQF can significantly attenuate RSV-induced asthma exacerbation. These effects may be mediated at least partially by regulating the balance between Th1 and Th2-Th17 responses.

Prognosis of patients with colorectal cancer (CRC) is generally poor because of the lack of simple, convenient, and noninvasive tools for CRC detection at the early stage. The discovery of microRNAs (miRNAs) and their different expression profiles among different kinds of diseases has opened a new avenue for tumor diagnosis. We built a serum microRNA expression profile signature and tested its specificity and sensitivity as a biomarker in the diagnosis of CRC. We also studied its possible role in monitoring the progression of CRC. We conducted a two phase case-control test to identify serum miRNAs as biomarkers for CRC diagnosis. Using quantitative reverse transcription polymerase chain reactions, we tested ten candidate miRNAs in a training set (30 CRCs vs 30 controls). Risk score analysis was used to evaluate the diagnostic value of the serum miRNA profiling system. Other independent samples, including 83 CRCs and 59 controls, were used to validate the diagnostic model. In the training set, six serum miRNAs (miR-21, let-7g, miR-31, miR-92a, miR-181b, and miR-203) had significantly different expression levels between the CRCs and healthy controls. Risk score analysis demonstrated that the six-miRNA-based biomarker signature had high sensitivity and specificity for distinguishing the CRC samples from cancer-free controls. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA signature profiles were 0.900 and 0.923 for the two sets of serum samples, respectively. However, for the same serum samples, the areas under the ROC curve used by the tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were only 0.649 and 0.598, respectively. The expression levels of the six serum miRNAs were also correlated with CRC progression. Thus, the identified six-miRNA signature can be used as a noninvasive biomarker for the diagnosis of CRC, with relatively high sensitivity and specificity.

The arrangement of plant cortical microtubules can reflect the physiological state of cells. However, little attention has been paid to the image quantitative analysis of plant cortical microtubules so far. In this paper, Bidimensional Empirical Mode Decomposition (BEMD) algorithm was applied in the image preprocessing of the original microtubule image. And then Intrinsic Mode Function 1 (IMF1) image obtained by decomposition was selected to do the texture analysis based on Grey-Level Cooccurrence Matrix (GLCM) algorithm. Meanwhile, in order to further verify its reliability, the proposed texture analysis method was utilized to distinguish different images of Arabidopsis microtubules. The results showed that the effect of BEMD algorithm on edge preserving accompanied with noise reduction was positive, and the geometrical characteristic of the texture was obvious. Four texture parameters extracted by GLCM perfectly reflected the different arrangements between the two images of cortical microtubules. In summary, the results indicate that this method is feasible and effective for the image quantitative analysis of plant cortical microtubules. It not only provides a new quantitative approach for the comprehensive study of the role played by microtubules in cell life activities but also supplies references for other similar studies.

Glutathione (GSH) was treated by pulsed electric field (PEF) processing to investigate its effect on antioxidant activity. The antioxidant activity of GSH was evaluated using 2,2-diphenyl-1-picrylhydrazy (DPPH) radical inhibition. A Box-Behnken design (BBD) with three independent variables, which were concentration, electric field intensity and pulse frequency was used to establish the regression equation of second-order response surface. Optimal conditions were as follows: GSH concentration 8.86mg/mL, electric field intensity 9.74kV/cm and pulse frequency 2549.08Hz. The DPPH radical inhibition increased from 81.83% to 97.40%. Near-infrared spectroscopy (NIR) and mid-infrared spectroscopy (MIR) were used to analyse the change of structure and functional groups of GSH.

We investigated the effects of respiratory syncytial virus (RSV) infections on ovalbumin (OVA)-challenged mice via regulation of Th17/Treg cell responses. BALB/c mice were challenged with OVA, followed by RSV infections twice. In OVA-challenged mice, the secretion of Th2/Th17-type cytokines, airway hyperresponsiveness and inflammation were significantly inhibited by initial RSV infection. Moreover, the in vivo findings demonstrated that initial RSV infection reversed the imbalance of Th17/Treg responses. In contrast, RSV re-infection strengthened Th2/Th17-type cytokine secretion, airway hyperresponsiveness, and inflammation, especially for lymphocyte infiltration in OVA-challenged mice. Meanwhile, RSV re-infection enhanced the imbalanced Th17/Treg responses. Upon all results reveal that RSV-induced respiratory infections may lead to dual effects pertaining to allergic airway inflammation by regulation of Th17/Treg responses.

Nuclear apoptosis-inducing factor 1 (NAIF1) was previously reported to induce apoptosis. Moreover, the expression of NAIF1 was significantly down-regulated in human gastric cancer tissues compared to adjacent normal tissues. However, the mechanism by which the NAIF1 gene induces apoptosis is not fully understood. Our results show that NAIF1 was minimally expressed in all the tested gastric cancer cell lines. Our data also demonstrates that NAIF1 is localized in the nuclei of cells as detected by monitoring the green fluorescence of NAIF1-GFP fusion protein using fluorescent confocal microscopy. Next, a comparative proteomic approach was used to identify the differential expression of proteins between gastric cancer cell lines MKN45/NAIF1 (-) and MKN45/NAIF1 (+). We found five proteins (proteasome 26S subunit 2, proteasome 26S subunit 13, NADH dehydrogenase Fe-S protein 1, chaperonin containing TCP1 subunit 3 and thioredoxin reductase 1) that were up-regulated and three proteins (ribonuclease inhibitor 1, 14-3-3 protein epsilon isoform and apolipoprotein A-I binding protein) that were down-regulated in the MKN45 cells overexpressing NAIF1. We also discovered that NAIF1 could induce cell cycle arrest at G1/S phase by altering the expression of cell cycle proteins cyclinD1, cdc2 and p21. The differentially expressed proteins identified here are related to various cellular programs involving cell cycle, apoptosis, and signal transduction regulation and suggest that NAIF1 may be a tumor suppressor in gastric cancer. Our research provides evidence that elucidates the role of how NAIF1 functions in gastric cancer.

The high incidence of MET oncogene activation in human malignancies has prompted researchers to develop MET inhibitors. As part of our efforts to developing effective and safe therapeutic agents against MET-dependent tumors, a pyridone-based class II MET inhibitor, namely, 1-(4-((2-amino-3-iodopyridin-4-yl)-oxy)-3-fluorophenyl)-N-(4-fluorobenzyl)-4-methoxy-6-oxo-1,6-dihydropyridine-3-carboxamide (3s), was identified. Knowledge of the binding mode of class II MET inhibitors led to the design of new inhibitors that utilize 2-pyridone to conformationally restrain key pharmacophoric groups within the molecule. Integrated molecular docking and SAR studies resulted in the discovery of a novel class of pyridone MET inhibitors with high potency (IC50 of 0.005 μM) and efficient selectivity (>5000 fold) to VEGFR-2, c-Kit and RET kinases.

Toxic cyanobacterial blooms are potential global threats to aquatic ecosystems and human health. The World Health Organization has set a provisional guideline limit of 1 μg/L microcystin-LR (MCLR) in freshwater. However, MCLR concentrations in several water bodies have exceeded this level. Despite this recommended human safety standard, MCLR-induced endocrine-disrupting effects and reproductive toxicity on male frog (Rana nigromaculata) were demonstrated in this study. Results showed that sperm motility and sperm count were significantly and negatively correlated with exposure time and concentration. By contrast, abnormal sperm rate was positively correlated with both parameters. Ultrastructural observation results revealed abnormal sperm morphologies, vacuoles in spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. These results indicated that MCLR could induce toxic effects on the reproductive system of frogs, significantly decrease testosterone content, and rapidly increase estradiol content. Prolonged exposure and increased concentration enhanced the relative expression levels of P450 aromatase and steroidogenic factor 1; thus, endocrine function in frogs was disrupted. This study is the first to demonstrate in vivo MCLR toxicity in the reproductive system of male R. nigromaculata. This study provided a scientific basis of the global decline in amphibian populations.