[Therapeutic strategies, practice, and prospect of a clinical cure for chronic hepatitis B in China].

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

[Lactate promotes HMGB1 phosphorylation and release via Akt signaling pathway in gastric cancer cells HGC-27].

Objective: To investigate the molecular mechanism of how lactate induces high mobility group box 1 (HMGB1) release. Methods: Gastric cancer HGC-27 cells were divided into the control group and the lactate group (The cells were treated with lactate for 6 h). The level of HMGB1 in the cell culture medium was detected by enzyme-linked immunosorbent assay (ELISA), the localization of HMGB1 was detected using laser confocal microscopy, and the nuclear translocation of HMGB1 was detected using the nucleoplasmic separation assay. The phosphorylation and acetylation levels of HMGB1 were determined by co-immunoprecipitation, and Western blot was used to measure the phosphorylation of Akt and protein kinase C (PKC). HGC-27 cells were first treated with lactate and LY294002, the inhibitor of Akt, and then the phosphorylation of HMGB1 and Akt was analyzed by co-immunoprecipitation and Western blot, respectively. The localization of HMGB1 in cells was detected by laser confocal microscopy. EdU and Transwell assays were used to detect the proliferation and migration abilities of HGC-27 cells, respectively. HGC-27 cells were then injected into the BALB/C null mice for subcutaneous tumor implantation. Mice in the lactate group were intraperitoneally injected with lactate (0.2 g/kg/2 d), while those in the control group were intraperitoneally injected with an equal amount of PBS for 20 consecutive days. ELISA was used to detect the HMGB1 levels in the blood samples taken from the medial canthus vein of the mice, while co-immunoprecipitation and Western blot were used to detect the phosphorylation of HMGB1 and Akt in tumor tissue proteins, respectively. Results: The release levels of HMGB1 in the lactate group were (2 995.00±660.91) pg/ml and (696.33±22.03) pg/ml, after lactate treatment for 6 h and 12 h, respectively, both higher than those in the control group (485.00±105.83) pg/ml (P<0.001 and P=0.028, respectively). After lactate treatment for 6 h, the relative expression of HMGB1 protein in the cytoplasm of HGC-27 cells was 1.13±0.09, higher than that of the control group (0.83±0.07, P=0.001), while the relative expression of HMGB1 in the nucleus was 0.79±0.06, lower than that of the control group (1.07±0.06, P=0.007). The phosphorylation level of HMGB1 reached 1.41±0.09, which was higher than that of the control group (0.97±0.10, P=0.031). The phosphorylation level of Akt was 11.16±0.06, higher than that of the control group (0.91±0.022, P=0.002). The phosphorylation level and nuclear translocation of HMGB1 induced by lactate decreased obviously after Akt inhibition; the proliferation and migration abilities induced by lactate were also obviously inhibited after Akt inhibition. In vivo, the HMGB1 level in the peripheral blood was (1 280.70±389.66) pg/ml in the lactate group, which was obviously higher than that in the control group (595.11±44.75) pg/ml (P=0.008), and the phosphorylation levels of HMGB1 and Akt in tumor tissues in the lactate group were obviously enhanced compared with the control group. Conclusion: Lactate induces HMGB1 release through enhancing HMGB1 phosphorylation via the Akt signaling pathway.

MDA5 attenuate autophagy in chicken embryo fibroblasts infected with IBDV.

1. The role of melanoma differentiation-associated protein 5 (MDA5) in infectious bursal disease virus (IBDV)-induced autophagy was studied in chicken embryos.2. Chicken embryo fibroblasts (CEF) were used as the research model and small interfering RNA (siRNA), western blot, indirect enzyme-linked immunosorbent assay (ELISA), real-time fluorescence quantitative polymerase chain reaction (PCR) and transmission electron microscopy were used to detect autophagy, IBDV replication, CEF damage, and activation of both MDA5 and its signalling pathway.3. The results showed that CEF infected with IBDV activated the intracellular MDA5 signalling pathway and caused autophagy via inactivation of the AKT/mTOR pathway. While autophagy promotes IBDV proliferation, MDA5 weakens IBDV-induced CEF autophagy thus inhibiting IBDV replication and protecting CEF cells.4. The results indicated that chMDA5 can be activated by IBDV and attenuate CEF autophagy caused by IBDV infection, thereby inhibiting IBDV replication. This study provided a foundation for further exploring the relationship between viruses, autophagy and the pathogenic mechanism of the MDA5 pathway involved in IBDV.

[Mechanism of advanced glycation end products inhibiting the proliferation of peripheral blood mononuclear cells and osteoblasts in rats].

OBJECTIVE: To explore the mechanism of nuclear factor-kappa B (NF-κB), phosphatidylinositol 3-kinase (PI3K)/protein kinase B(PKB/Akt) and mitogen-activated protein kinase (MAPK) signaling pathways after intervention of advanced glycosylation end products (AGEs) in peripheral blood mononuclear cells (PBMCs) and osteoblasts (OB) in rats, so as to provide certain experimental basis and theoretical basis for further research on the clinical treatment of periodontal tissue inflammation caused by diabetes mellitus. METHODS: AGEs were prepared, PBMCs and OB were isolated and cultured in vitro. CCK-8 was used to detect the cell viability intervened by different concentrations and time of AGEs. Western blot and qRT-PCR were used to detect the expression changes of genes related to NF-κB, PI3K/PKB and MAPK signaling pathways. RESULTS: OB and PBMCs were successfully isolated and cultured in vitro. The activity of PBMCs and OB cells was significantly correlated with the concentration, time and interaction of AGEs. With the increase of AGEs concentration and time, the activity of PBMCs and OB cells significantly decreased (P < 0.001). AGEs stimulation significantly increased the expression of NF-κB in PBMCs and the contents of tumor necrosis factor α(TNF-α), interleukin-1ß(IL-1ß) (P < 0.01). TNF-α, IL-1ß levels were significantly reduced after inhibition of NF-κB pathway (P < 0.01). NF-κB p65, JNK, and p38 phosphorylated and non-phosphorylated proteins increased significantly after AGEs stimulation of OB (P < 0.05). The phosphorylated protein expression of IκB was significantly increased, while the expression of non-phosphorylated protein was decreased (P < 0.01).The expressions of NF-κB p65, JNK, and IκB were significantly increased at the mRNA levels, and the expressions of IκB mRNA were significantly decreased (P < 0.05). There was no difference in the expression of Akt in either phosphorylated or non-phosphorylated proteins or at the mRNA level (P>0.05). With the addition of MAPK signaling pathway inhibitors, the phosphorylation and non-phosphorylated protein expressions of NF-κB p65, p38 and JNK were significantly reduced, and the phosphorylated protein of IκB was significantly decreased and the non-phosphorylated protein was significantly increased compared with the group with AGEs alone (P < 0.05). The results of qRT-PCR showed that the expression of IκB increased significantly after the addition of the JNK pathway blocker (P < 0.05), and the expression of NF-κB p65, p38 and JNK decreased, but the difference was not significant (P>0.05). While NF-κB p65, p38 and JNK were significantly decreased and IκB was significantly increased in the AGEs group after the addition of the p38 pathway blocker (P < 0.05). At this time, there was still no significant change in the expression of Akt at the protein level and mRNA level (P>0.05). CONCLUSION: AGEs inhibit the proliferation of PBMCs and OB, and the NF-κB and MAPK pathways are likely involved in regulating this process, but not the PI3K/PKB pathway.

Effect of pH on functional, gas sensing and antimicrobial properties of bio-nanocomposite gelatin film for food packaging application.

A bio-nanocomposite film is a polymer blend with nanofiller dispersed in a biopolymer matrix. The aim of this study is to investigate the functional, gas sensing and antimicrobial properties of bio-nanocomposite films incorporated with chicken skin gelatin/ tapioca starch/zinc oxide at different pH levels (pH 4, 6, 7 and 8). Bio-nanocomposite films were prepared using a casting technique followed by the characterization of their functional, gas sensing and antimicrobial properties. Film formulations with pH at different levels showed increased thickness, colour and water vapour permeability (WVP) (p < 0.05). In addition, the increase of pH in films in chicken skin gelatin bio-nanocomposite films increased the tensile strength (TS), while decreasing the elongation at break (EAB). The highest response for ammonia gas in chicken skin gelatin bio-nanocomposite films was obtained at pH 7, with quick response time (τres) within 10 s. The inhibition zone of Staphylococcus aureus in chicken skin gelatin bio-nanocomposite films increased with increasing pH levels. Overall, chicken skin gelatin bio-nanocomposite films with a pH level of 8 were found to have the optimal formulation, with the highest values in thickness, and TS, with the lowest values for WVP and EAB. In conclusion, bio-nanocomposite chicken skin gelatin films with an alkaline pH are a superior packaging material.

Nanomaterials Derived from Fungal Sources-Is It the New Hype?

Greener alternatives to synthetic polymers are constantly being investigated and sought after. Chitin is a natural polysaccharide that gives structural support to crustacean shells, insect exoskeletons, and fungal cell walls. Like cellulose, chitin resides in nanosized structural elements that can be isolated as nanofibers and nanocrystals by various top-down approaches, targeted at disintegrating the native construct. Chitin has, however, been largely overshadowed by cellulose when discussing the materials aspects of the nanosized components. This Perspective presents a thorough overview of chitin-related materials research with an analytical focus on nanocomposites and nanopapers. The red line running through the text emphasizes the use of fungal chitin that represents several advantages over the more popular crustacean sources, particularly in terms of nanofiber isolation from the native matrix. In addition, many ß-glucans are preserved in chitin upon its isolation from the fungal matrix, enabling new horizons for various engineering solutions.

[Endoscopic features and clinical correlation analysis of 24 patients with Cronkhite-Canada syndrome].

Objective: To clarify the endoscopic changes prior to corticosteroid therapy in Cronkhite-Canada syndrome (CCS) patients and to explore the correlation between endoscopic features and clinical characteristics. Methods: A total of 24 CCS patients who were hospitalized in Peking Union Medical College Hospital from January 1999 to June 2019 and underwent gastroscopy and colonoscopy before corticosteroid therapy were retrospectively enrolled. The endoscopic images were re-interpreted. The demographic characteristics, clinical manifestations, laboratory tests and histopathological data were collected and analyzed. Results: Of all 24 patients, 15 (62.5%) were male and 9(37.5%) were female, with an average age of (59±10) years and disease course of 6 (1~36) months. Based on the endoscopic findings, the percentages of stomach, colon, duodenum, rectum and terminal ileum involvement were 100%, 100%, 95.7%, 66.7% and 50.0% respectively. Gastric involvement was more severe in the lower part of the body and the antrum of the stomach, while the cardia and the fundus were spared in 5 (20.8%) cases. Colonic involvement was more severe in the right colon. No patient showed remarkable esophageal involvement. The typical appearance under endoscopy were diffuse mucosal hyperemia and edema with polyps or nodular changes. The lesions may have mulberry-like or imbricate changes in severe cases. Lymphatic dilation in the duodenum was found in 47.8% patients. Most of the polyps were pedunculated or sub-pedunculated, with occasionally seen sessile polyps in the colon. The pit patterns of the 12 resected colon polyps in 11 patients could be classified as Kudo type Ⅲ(S), Ⅲ(L), Ⅳ and Ⅴ(I), among which 2 tubular adenomas had the Kudo type Ⅲ(L). Other resected polyps were hyperplastic polyps or CCS polyps. The disease duration prior to diagnosis was positively correlated with the maximum diameter of colon polyps (r=0.625, P=0.006). Serum albumin levels in patients with whole stomach involvement were significantly lower than those in patients with cardia spared [(29±8) g/L vs (37±5) g/L, P=0.034]. Conclusions: The typical initial endoscopic finding of CCS is multiple polyps or nodular changes on the background of diffuse hyperemia and edema lining the gastric, duodenal and colonic mucosa. Lymphatic dilatation in the duodenum could also be found. Some endoscopic features are correlated to clinical characteristics.

Head-to-head trials of systemic psoriasis therapies: a systematic review of study design and maximum acceptable treatment differences.

There is increasing use of head-to-head clinical trials in dermatology when establishing the efficacy of a new treatment. Active comparator trials (ACTs) can be classified into three distinct study trial designs: non-inferiority, equivalence and superiority. A better understanding of the statistical parameters, such as acceptable treatment differences (also known as the margin or delta), is necessary to properly design and interpret findings of active comparator trials (ACTs) in the field of dermatology. Therefore, the objective of this study was to summarize the maximum acceptable treatment differences in clinical trials that examine the efficacy of an oral or biologic psoriasis therapy with an active comparator. We conducted a systematic search using MEDLINE, Scopus, EMBASE, Cochrane Central Register of Controlled Trials, LILACS, Web of Science and ClinicalTrials.gov from inception to 31 August 2017. All ACTs with adult participants that had a primary outcome of the Psoriasis Area and Severity Index score were included. Bibliographies of articles were further reviewed. Two investigators independently assessed for article inclusion and separately completed data extraction of predefined data points. When there was a disagreement, a third investigator was consulted. Of the 49 ACTs included, there were 13 superiority, eight non-inferiority and seven equivalence trials. Another 21 studies had inadequate information for classification. All of the non-inferiority trials reported the margin, one of the superiority and six of the equivalence trials stated the treatment difference explicitly. For superiority trials, acceptable treatment differences ranged from 14% to 20%. The non-inferiority studies reported lower bound margins ranging from -20% to -10%. The equivalence trials reported upper and lower bound margins ranging from ±12.5% to ±18%. The results demonstrate the need for harmonization in the conduct of dermatological clinical trials and in the approaches of reporting research parameters.

Interpretation of liver stiffness measurement-based approach for the monitoring of hepatitis B patients with antiviral therapy: A 2-year prospective study.

Liver biopsy is not routinely performed in treated chronic hepatitis B. Liver stiffness measurement has been validated for noninvasive liver fibrosis assessment in pretreatment chronic hepatitis B but has not been assessed for fibrosis monitoring during antiviral therapy. Liver stiffness was systemically monitored by Fibroscan® every 6 months in a cohort of patients with hepatitis B receiving antiviral therapy and compared with liver biopsies at baseline and week 104. A total of 534 hepatitis B e antigen-positive treatment-naive patients receiving telbivudine-based therapy with qualified liver stiffness measurement at baseline and week 104 were analyzed, 164 of which had adequate paired liver biopsies. Liver stiffness decreased rapidly (-2.2 kPa/24 weeks) in parallel with alanine aminotransferase (ALT) from 8.6 (2.6-49.5) kPa at baseline to 6.1 (2.2-37.4) kPa at week 24. Interestingly, liver stiffness decreased slowly (-0.3 kPa/24 weeks) but continually from week 24 to week 104 (6.1 vs 5.3 kPa, P < .001) while ALT levels remained stable within the normal range. More importantly, liver stiffness declined significantly irrespective of baseline ALT levels and liver necroinflammation grades. From baseline to week 104, the proportion of patients with no or mild fibrosis (Ishak, 0-2) increased from 74.4% (122/164) to 93.9% (154/164). Multivariate analysis revealed that percentage decline of 52-week liver stiffness from baseline was independently associated with 104-week liver fibrosis regression (odds ratio, 3.742; P = .016). Early decline of 52-week liver stiffness from baseline may reflect the remission of both liver inflammation and fibrosis and was predictive of 104-week fibrosis regression in treated patients with chronic hepatitis B.

Nivolumab versus ipilimumab in the treatment of advanced melanoma: a critical appraisal: ORIGINAL ARTICLE: Wolchok JD, Chiarion-Sileni V, Gonzalez R et al. Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 2017; 377:1345-56.

AIM: To show whether either nivolumab in combination with ipilimumab or nivolumab monotherapy vs. ipilimumab monotherapy extends overall survival (OS) or progression-free survival (PFS) in adults with previously untreated, advanced melanoma. SETTING AND DESIGN: The trial was conducted at 137 sites in 21 countries. Randomization (n = 945; 1 : 1 : 1 ratio) was stratified according to metastasis stage, BRAF mutation status and programmed death ligand 1 status. STUDY EXPOSURE: Adults were randomized to one of the following: nivolumab plus ipilimumab every 3 weeks for four doses, followed by nivolumab every 2 weeks; nivolumab every 2 weeks plus placebo; or ipilimumab every 3 weeks for four doses plus placebo. Treatment was continued until progression, unacceptable toxicity or withdrawal. OUTCOMES: OS, PFS and objective response rate were determined. Patients were also assessed for adverse events. The primary end points of interest were OS and PFS, comparing either the nivolumab plus ipilimumab group or the nivolumab-only group with the patients treated with ipilimumab only. RESULTS: At 3 years, the OS rates were 58%, 52% and 34% for the nivolumab plus ipilimumab, the nivolumab monotherapy and the ipilimumab monotherapy groups, respectively. For the nivolumab plus ipilimumab group, the median OS was not reached at the time of analysis. For the nivolumab-only group, the median OS was 37·6 months, and the ipilimumab-only group had a median OS of 19·9 months. The hazard ratio for death was 0·55 [95% confidence interval (CI) 0·45-0·69; P < 0·001] comparing nivolumab plus ipilimumab with ipilimumab, and 0·65 (95% CI 0·53-0·80; P < 0·001) comparing nivolumab with ipilimumab. The PFS rates at 3 years were 39% for the nivolumab plus ipilimumab group, 32% for the nivolumab monotherapy group and 10% for the ipilimumab monotherapy group, with 95% CIs for the two nivolumab groups that did not overlap with that for ipilimumab alone. CONCLUSIONS: Among patients with advanced melanoma, significantly longer OS and PFS occurred with the combination of nivolumab plus ipilimumab or with nivolumab alone compared with ipilimumab alone. Furthermore, survival outcomes favoured the nivolumab-containing groups over the ipilimumab group in subgroup analyses.

A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT).

BACKGROUND: Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. OBJECTIVES: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX. METHODS: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day). RESULTS: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation. CONCLUSIONS: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.

Polymorphism of the androgen receptor gene CAG repeat sequence and male climacteric syndrome.

The aim of this study was to analyze the association between polymorphism of the androgen receptor (AR) gene CAG repeat sequence and the climacteric syndrome in men. The study was performed in 103 males with climacteric syndrome and 111 males without the clinical syndrome of climacteric, aged between 40 and 70 years. DNA sequencing of the CAG repeat sequence in the N-terminal domain of the first exon of the AR gene was analyzed. The AR allele length ranged from 18-34 CAG repeats in males with climacteric syndrome. The average value of CAG repeat was 24.7±2.58. However, the corresponding values ranged from 15-24 CAG repeat in control group and the average value of CAG repeat was 21.25±2.63. There was a significant difference of the number of CAG repeat between the two groups. The occurrence of male climacteric syndrome was related to the CAG repeat number of androgen receptor gene, and the male patients with more CAG repeats had higher risk of clinical syndrome of climacteric. The detection of CAG repeat number of AR gene might be helpful for the prediction of clinical syndrome of climacteric.

The incidence of military training-related injuries in Chinese new recruits: a systematic review and meta-analysis.

INTRODUCTION: Training-related injuries are the main reason for disability, long-term rehabilitation, functional impairment and premature discharge from military service. The aim of this study was to identify the incidence of injuries in the training of Chinese new recruits via a systematic review of the literature. METHOD: A systematic review and meta-analysis was conducted to evaluate the combined incidence of military training-related injuries in Chinese new recruits. The electronic databases of full-text journals were searched, and the Loney criteria were used to assess the quality of eligible articles. Summary estimates were obtained using random-effects models. Subgroup analyses and publication bias tests were performed. RESULTS: Fifty-five eligible articles representing 109 611 Chinese new recruits met the inclusion criteria, of which 21 253 recruits were clinically diagnosed with military training-related injuries. The combined incidence of military training-related injuries in Chinese new recruits was found to be 21.04%. CONCLUSIONS: An increased incidence of training injuries was found in more recent years, underscoring the need for further research on the risk factors associated with their causation.

Intermittent Dissipation and Heating in 3D Kinetic Plasma Turbulence.

High resolution, fully kinetic, three dimensional (3D) simulation of collisionless plasma turbulence shows the development of turbulence characterized by sheetlike current density structures spanning a range of scales. The nonlinear evolution is initialized with a long wavelength isotropic spectrum of fluctuations having polarizations transverse to an imposed mean magnetic field. We present evidence that these current sheet structures are sites for heating and dissipation, and that stronger currents signify higher dissipation rates. The analyses focus on quantities such as J·E, electron, and proton temperatures, and conditional averages of these quantities based on local electric current density. Evidently, kinetic scale plasma, like magnetohydrodynamics, becomes intermittent due to current sheet formation, leading to the expectation that heating and dissipation in astrophysical and space plasmas may be highly nonuniform. Comparison with previous results from 2D kinetic simulations, as well as high frequency solar wind observational data, are discussed.

Nucleotide-binding oligomerization domain 1 regulates Porphyromonas gingivalis-induced vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 expression in endothelial cells through NF-κB pathway.

BACKGROUND AND OBJECTIVE: Porphyromonas gingivalis has been shown to actively invade endothelial cells and induce vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) overexpression. Nucleotide-binding oligomerization domain 1 (NOD1) is an intracellular pattern recognition reporter, and its involvement in this process was unknown. This study focused on endothelial cells infected with P. gingivalis, the detection of NOD1 expression and the role that NOD1 plays in the upregulation of VCAM-1 and ICAM-1. MATERIAL AND METHODS: The human umbilical vein endothelial cell line (ECV-304) was intruded by P. gingivalis W83, and cells without any treatment were the control group. Expression levels of NOD1, VCAM-1, ICAM-1, phosphorylated P65 between cells with and without treatment on both mRNA and protein levels were compared. Then we examined whether mesodiaminopimelic acid (NOD1 agonist) could increase VCAM-1 and ICAM-1 expression, meanwhile, NOD1 gene silence by RNA interference could reduce VCAM-1, ICAM-1 and phosphorylated P65 release. At last, we examined whether inhibition of NF-κB by Bay117082 could reduce VCAM-1 and ICAM- 1 expression. The mRNA levels were measured by real-time polymerase chain reaction, and protein levels by western blot or electrophoretic mobility shift assays (for phosphorylated P65). RESULTS: P. gingivalis invasion showed significant upregulation of NOD1, VCAM-1 and ICAM-1. NOD1 activation by meso-diaminopimelic acid increased VCAM-1 and ICAM-1 expression, and NOD1 gene silence reduced VCAM-1 and ICAM-1 release markedly. The NF-κB signaling pathway was activated by P. gingivalis, while NOD1 gene silence decreased the activation of NF-κB. Moreover, inhibition of NF-κB reduced VCAM-1 and ICAM-1 expression induced by P. gingivalis in endothelial cells. CONCLUSION: The results revealed that P. gingivalis induced NOD1 overexpression in endothelial cells and that NOD1 played an important role in the process of VCAM-1 and ICAM-1 expression in endothelial cells infected with P. gingivalis through the NF-κB signaling pathway.

Anisotropy in solar wind plasma turbulence.

A review of spectral anisotropy and variance anisotropy for solar wind fluctuations is given, with the discussion covering inertial range and dissipation range scales. For the inertial range, theory, simulations and observations are more or less in accord, in that fluctuation energy is found to be primarily in modes with quasi-perpendicular wavevectors (relative to a suitably defined mean magnetic field), and also that most of the fluctuation energy is in the vector components transverse to the mean field. Energy transfer in the parallel direction and the energy levels in the parallel components are both relatively weak. In the dissipation range, observations indicate that variance anisotropy tends to decrease towards isotropic levels as the electron gyroradius is approached; spectral anisotropy results are mixed. Evidence for and against wave interpretations and turbulence interpretations of these features will be discussed. We also present new simulation results concerning evolution of variance anisotropy for different classes of initial conditions, each with typical background solar wind parameters.

Immunomodulatory effect of bone marrow mesenchymal stem cells on T lymphocytes in patients with decompensated liver cirrhosis.

We explored the immunomodulatory effects of bone marrow mesenchymal stem cells (BMSCs) on peripheral blood T lym-phocytes in patients with decompensation stage, hepatitis B-associated cirrhosis. MSCs from nine patients were analyzed by flow cytometry. Peripheral blood lymphocytes were isolated for fluorescent staining. Following stimulation by phytohemagglutinin (PHA), peripheral blood lymphocytes were co-cultured with BMSCs in serum and divided into four groups: (1) BMSC + lymphocyte + PHA contact culture group; (2) BMSC + lymphocyte + PHA non-contact culture group; (3) lym-phocyte + PHA positive control group; and (4) lymphocyte-only negative control group. Lymphocyte proliferation and frequencies of CD4(+)CD25(+)CD127(-) Tregs and CD4(+)CD8(-)IL-17(+) (Th17) cells were de-tected. Cell proliferation in groups 1 and 2 declined compared with group 3 (P < 0.01), and was notably higher than in group 4 (P < 0.01). CD4(+)CD25(+)CD127(-) Tregs frequencies in groups 1 and 2 were higher than in groups 3 and 4. In an intra-group comparison before and after culture, Th17 cell frequencies in groups 1 and 2 were higher than in group 4 (P < 0.01), but lower than in group 3 (P < 0.01). The Treg/Th17 ratio in groups 1 and 2 increased (P < 0.01), but did not change signifi-cantly in groups 3 and 4 (P > 0.05). In a comparison between groups after culture, the Treg/Th17 ratio in groups 1 and 2 increased more than in groups 3 and 4 (P < 0.01). BMSCs from cirrhotic patients can inhibit the proliferation of peripheral blood T lymphocytes, upregulate the ex-pression of CD4(+)CD25(+)CD127(-) Tregs, and improve Treg/Th17 imbal-ance. The mechanism by which this takes place may be associated with immunomodulatory effects induced by the secretion of soluble factors.

High expression of HIF-2α and its anti-radiotherapy effect in lung cancer stem cells.

Hypoxia-inducible factor-2 alpha (HIF-2α) has been shown to regulate cell stemness, although the expression and effects of HIF-2α in lung cancer stem cells remained unclear. This study investigated HIF-2α expression in lung cancer stem cells, as well as the relationship between HIF-2α expression and radioresistance in lung cancer cells. Stem-like cells (CD133(+)) in the non-small-cell lung cancer cell line A549 were enriched by serum-free culture conditions, and CD133(+) cells were sorted via fluorescence-activated cell sorting. A549 cells were treated with middle-infrared radiation, and the level of HIF-2α expression was determined by a quantitative polymerase chain reaction assay and western blot analysis. The level of HIF-2α expression in tissue sections from 50 cases of clinically confirmed non-small-cell lung cancer was determined via immunohistochemical analysis, and its correlation with prognosis after radiotherapy was analyzed. HIF-2α levels in CD133(+) cells were significantly higher than those in CD133(-) cells (P = 0.032). However, after radiation treatment, these levels were significantly upregulated in both CD133(+) and CD133(-) cells (P = 0.031 and P = 0.023, respectively). After irradiation, the proportions of apoptotic, dead, and autophagic CD133(+) A549 cells were considerably lower than those of CD133(-) A549 cells (P < 0.05). Furthermore, the recovery of carcinoembryonic antigen to pre-radiation levels was more rapid in lung cancer patients with high levels of HIF-2α expression, and these patients had shorter survival times (P = 0.018). HIF-2α is highly expressed in lung cancer stem cells, which may lead to radioresistance. In conclusion, HIF-2α is a potential prognostic marker for lung cancer.