Survival analysis of comprehensive treatment in Chinese patients with metastatic melanoma: A retrospective analysis.

BACKGROUND: Most of the current progression of immune checkpoint inhibitors for malignant melanoma is based on data from Caucasians in Western countries, but the benefit of Chinese patients is limited, mainly due to different pathological subtypes. The patients in western countries are mainly skin melanoma (about 90%), while the acral and mucosal types are dominant in China, accounting for 41.8% and 22.6% respectively. Acral and mucosal melanoma have lower response rates to immunotherapy and chemotherapy. OBJECTIVE: Whether immune checkpoint inhibitors can improve the survival of Chinese patients with malignant melanoma, therefore, we conducted a retrospective analysis. METHODS: We analyzed 53 patients with metastatic melanoma treated in our hospital to evaluate the efficacy and safety of PD-1 mAb in Chinese patients with metastatic melanoma, and performed univariate and multivariate analyses of prognostic factors that may affect overall survival (OS). RESULTS: In a study of 125 patients with advanced malignant melanoma, 53 patients participated, with a median follow-up of 16 months. Among these, 69.8% died, and 30.2% remained on treatment. Median progression-free survival (PFS) was 6 months, and median OS was 19 months. Patients treated with immune checkpoint inhibitors had improved outcomes, with a median PFS of 7 months and a median OS of 24 months. Patients with bone metastasis and aberrant Lactate dehydrogenase (LDH) post-treatment had worse prognoses, while immunotherapy was a protective factor. Subgroup analysis showed the benefits of immunotherapy across various patient characteristics. No unexpected toxicities were observed. CONCLUSION: The study highlights the efficacy of immune checkpoint inhibitors, particularly PD-1 mAb, in improving survival outcomes for Chinese patients with metastatic melanoma.

The transcription factor GhWRKY70 from gossypium hirsutum enhances resistance to verticillium wilt via the jasmonic acid pathway.

BACKGROUND: The WRKY transcription factors play significant roles in plant growth, development, and defense responses. However, in cotton, the molecular mechanism of most WRKY proteins and their involvement in Verticillium wilt tolerance are not well understood. RESULTS: GhWRKY70 is greatly up-regulated in cotton by Verticillium dahliae. Subcellular localization suggests that GhWRKY70 is only located in the nucleus. Transcriptional activation of GhWRKY70 further demonstrates that GhWRKY70 function as a transcriptional activator. Transgenic Arabidopsis plants overexpressing GhWRKY70 exhibited better growth performance and higher lignin content, antioxidant enzyme activities and jasmonic acid (JA) levels than wild-type plants after infection with V. dahliae. In addition, the transgenic Arabidopsis resulted in an enhanced expression level of AtAOS1, a gene related to JA synthesis, further leading to a higher JA accumulation compared to the wild type. However, the disease index (DI) values of the VIGS-treated cotton plants with TRV:WRKY70 were also significantly higher than those of the VIGS-treated cotton plants with TRV:00. The chlorophyll and lignin contents of TRV:WRKY70 plants were significantly lower than those of TRV:00 plants. GhAOS1 expression and JA abundance in TRV:WRKY70 plants were decreased. The GhWRKY70 protein was confirmed to bind to the W-box element in the promoter region of GhAOS by yeast one-hybrid assay and transient expression. CONCLUSION: These results indicate that the GhWRKY70 transcription factor is a positive regulator in Verticillium wilt tolerance of cotton, and may promote the production of JA via regulation of GhAOS1 expression.

Glycolate oxidase gene family identification and functional analyses in cotton resistance to Verticillium wilt.

Glycolate oxidase (GOX) plays an important role in the regulation of photorespiration and photosynthesis in plants. However, as one of the main enzymes to produce the second messenger hydrogen peroxide (H2O2), its functions in response to pathogens are still poorly understood. In this study, we carried out genome-wide identification, and 14 GOX genes were identified in Gossypium hirsutum. These GOX genes are located on 10 chromosomes and divided into hydroxyacid-oxidases (HAOX) and GOX groups. After infection with Verticillium dahliae Kleb., six GOX gene expression levels were changed. Moreover, H2O2, salicylic acid (SA), and the content and activity of GOX increased in cotton. GhHAOX2-D-silenced plants showed more wilting than control plants after infection with V. dahliae. Additionally, H2O2 accumulation and SA content were reduced in GhHAOX2-D-silenced plants. The expression levels of GhPAL, GhPAD4, and GhPR1 and the lignin content of the silenced plants were significantly lower than those of the control plants. These results indicate that GhHAOX2-D is a positive regulator of Verticillium wilt tolerance in cotton and may promote H2O2 accumulation via the synergistic effects of GOX genes and SA. Collectively, GOX genes play an important role in cotton resistance to Verticillium wilt.

Endoscopic follow-up of mucosal defect after hot versus cold snare polypectomy in animal model.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) has received increasing attention in recent years, but few studies have assessed defect repair after polypectomy. Therefore, we compared the repair of mucosal defect after CSP and hot snare polypectomy (HSP) in a rabbit model. METHODS: Resection of normal colonic mucosa using both HSP and CSP were performed in 40 male New Zealand white rabbits by an experienced endoscopist. Follow-up colonoscopy was performed after 7 and 15 days by another endoscopist. We assessed mucosal defect repair, status of healing, scar formation, and intraoperative or delayed complications (including perforation and bleeding). RESULTS: Eight animals died of intraoperative or delayed perforation; follow-up colonoscopy was performed in 32 animals. On follow-up colonoscopy at 7 days after operation, 78.1% cases in the CSP group showed healing of mucosal defect compared with none in the HSP group (P < 0.001); mucosal repair score in the CSP group was significantly higher than HSP group (P < 0.001). On follow-up colonoscopy at 15 days, mucosal defect after CSP had completely healed in all cases (100%) versus 96.9% after HSP (P = 0.313). Among these healed defects, scar formation was observed in 2 of 32 cases in the CSP group compared with 19 of 31 in the HSP group (P < 0.001). Intraoperative perforation rate was significantly higher in the HSP group (15% vs 2.5%; P = 0.048). CONCLUSIONS: Mucosal defect repair after CSP is quicker compared with HSP and is more likely to result in scarless healing. HSP is more likely to cause perforation in the thin colon walls.

Nomogram predicting prostate cancer in patients with negative prebiopsy multiparametric magnetic resonance.

Aim: To build two nomograms for predicting the possibilities of prostate cancer (PCa) and clinically significant PCa (csPCa) in patients with negative prebiopsy multiparametric MRI (mpMRI). Methods: The independent predictors associated with PCa or csPCa in patients with negative mpMRI were determined and served in the construction of the two nomograms. Results: The nomogram predicting PCa consisted of age, positive digital rectal examination, free/total prostate-specific antigen (PSA) ratio and PSA density, while age, positive digital rectal examination and PSA density comprised the nomogram predicting csPCa. The negative predictive value of mpMRI for PCa and csPCa improved from 77.1 and 87.5% to 90.4 and 96.1%, respectively, in the training cohort (n = 376) and from 81.9 and 89.0% to 91.8 and 96.5%, respectively, in the validation cohort (n = 127) when combined with the two nomograms. Conclusion: The negative predictive value of negative mpMRI for the detection of PCa or csPCa was improved with the results of the nomograms.

When a patient has an elevated PSA level, a prostate biopsy is frequently required to diagnose prostate cancer (PCa). However, many men are not diagnosed with PCa or have indolent PCa, which means they are subjected to unnecessary biopsies that may lead to bleeding, pain and infection. With the development of multiparametric MRI (mpMRI), more biopsy-naive patients will undergo mpMRI to minimize unnecessary biopsies. Nonetheless, some patients with negative mpMRI findings but elevated levels of prostate-specific antigen still undergo prostate biopsies to rule out the possibility of MRI-invisible cancer, driving a potential for unnecessary biopsies. Therefore we developed two prediction models to estimate the likelihood of PCa and clinically significant PCa in patients with negative mpMRI, which may help to select optimal strategies to avoid unnecessary biopsies.

CircVAPA exerts oncogenic property in non-small cell lung cancer by the miR-876-5p/WNT5A axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is one of the most fatal malignant tumors. Emerging studies have clarified the crucial roles of circular RNAs (circRNAs) in the tumorigenesis of cancers. CircVAPA was demonstrated to function in some human cancers. The present study aimed to investigate the role of circVAPA in NSCLC. METHODS: A quantitative real-time polymerase chain reaction was used to measure the expression of genes. Actinomycin D and RNase R were employed to examine the stability of circVAPA. Cell-counting kit-8, 5-ethynyl-2'-deoxyuridine, Transwell and sphere formation assays, and well as western blot analysis, were conducted to examine the changes of NSCLC cells in response to circVAPA knockdown. A luciferase reporter assay was conducted for the molecular mechanism. RESULTS: Our findings demonstrated high expression of circVAPA in tissues and cell lines of NSCLC. Knockdown of circVAPA had a suppressive effect on cell proliferation, migration, invasion and stemness, and also inhibited tumor growth in vivo. Mechanistically, circVAPA acted as a competing endogenous RNA to up-regulate WNT5A by sponging miR-876-5p. Moreover, circVAPA activated Wnt/ß-catenin signaling by up-regulation of WNT5A. Rescue assays showed that silencing of miR-876-5p or overexpression of WNT5A reversed the circVAPA knockdown-mediated inhibition on cellular processes in NSCLC. CONCLUSIONS: CircVAPA promotes aggressive phenotypes of NSCLC cells by the miR-876-5p/WNT5A axis activating Wnt/ß-catenin signaling.

LncRNA-H19 silencing suppresses synoviocytes proliferation and attenuates collagen-induced arthritis progression by modulating miR-124a.

OBJECTIVES: Long non-coding RNA H19 (lncRNA-H19) is highly expressed in fibroblast-like synoviocytes (FLS) from patients with RA. The present study aimed to clarify the pathological significance and regulatory mechanisms of lncRNA-H19 in FLS. METHODS: Mice with CIA were locally injected with LV-shH19. The progression of CIA was explored by measuring arthritic index (AI), paw thickness (PT) and histologic analysis. The growth and cell cycle of human synoviocyte MH7A were assessed by CCK-8 and flow cytometric analysis. The putative binding sites between lncRNA-H19 and miR-124a were predicted online, and the binding was identified by luciferase assay. RT-qPCR, Western blot and luciferase assay were performed to explore the molecular mechanisms between liver X receptor (LXR), lncRNA-H19, miR-124a and its target genes. RESULTS: The expression of lncRNA-H19 was closely associated with the proliferation of synoviocytes and knockdown of lncRNA-H19 significantly ameliorated the progression of CIA, reflected by decreased AI, PT and cartilage destruction. Notably, lncRNA-H19 competitively bound to miR-124a, which directly targets CDK2 and MCP-1. It was confirmed that lncRNA-H19 regulates the proliferation of synoviocytes by acting as a sponge of miR-124a to modulate CDK2 and MCP-1 expression. Furthermore, the agonists of LXR inhibited lncRNA-H19-mediated miR-124a-CDK2/MCP-1 signalling pathway in synoviocytes. The 'lncRNA-H19-miR-124a-CDK2/MCP-1' axis plays an important role in LXR anti-arthritis. CONCLUSION: Regulation of the miR-124a-CDK2/MCP-1 pathway by lncRNA-H19 plays a crucial role in the proliferation of FLS. Targeting this axis has therapeutic potential in the treatment of RA and may represent a novel strategy for RA treatment.

Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis.

Gefitinib, erlotinib and afatinib are three widely used epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for treating advanced non-small cell lung cancer (NSCLC) with proven efficacy. We undertook a systematic review and meta-analysis to synthesize existing studies with direct comparisons of EGFR TKIs in NSCLC in terms of both efficacy and safety. Eight randomized trials and 82 cohort studies with a total of 17,621 patients were included for analysis. Gefitinib and erlotinib demonstrated comparable effects on progression-free survival (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.95 to 1.04), overall survival (HR, 0.99; 95% CI, 0.93 to 1.06), overall response rate (risk ratio [RR], 1.05; 95% CI, 1.00 to 1.11), and disease control rate (RR, 0.98; 95% CI, 0.96 to 1.01), which did not vary considerably with EGFR mutation status, ethnicity, line of treatment, and baseline brain metastasis status. Gefitinib was associated with more grade 3/4 liver dysfunction, but tended to cause lower rates of dose reduction, treatment discontinuation, total grade 3/4 adverse events (RR, 0.78; 95% CI 0.65 to 0.94), and a number of specific adverse events such as rash and diarrhea. No solid evidence was found that afatinib had greater efficacy than gefitinib or erlotinib in first-line treatment of EGFR-mutant NSCLC. However, afatinib was more effective than erlotinib as second-line treatment of patients with advanced squamous cell carcinoma. The grade 3/4 adverse events rate of afatinib was comparable to that of erlotinib but higher than that of gefitinib.

LncRNA Gm4419 contributes to OGD/R injury of cerebral microglial cells via IκB phosphorylation and NF-κB activation.

Ischemic stroke is one of major causes of adult morbidity. Recent studies have shown that over-activated microglial cells play a critical role in aggravating cerebral oxygen glucose deprivation/reoxygenation (OGD/R) damage by releasing excessive inflammatory cytokines. However, the involving mechanisms are not distinct yet. Long non-coding RNAs (lncRNAs) have been reported to in participate in lots of complicated biological processes. Our understandings of the relationship between lncRNAs and OGD/R injury are largely limited. In this study, we demonstrated that a lncRNA Gm4419 functioned as a crucial mediator in the activation of NF-κB signaling pathway, causing neuroinflammation damage during OGD/R. Gm4419 was abnormally up-regulated in OGD/R-treated microglial cells. We found that the high level of Gm4419 promoted the phosphorylation of IκBα by physically associating with IκBα, therefore, led to increased nucleus NF-κB levels for the transcriptional activation of TNF-α, IL-1ß and IL-6. In addition, we also demonstrated that knockdown of Gm4419 functioned as NF-κB inhibitor in OGD/R microglial cells, showing that down-regulation of Gm4419 had protective role against OGD/R injury. In summary, Gm4419 is required for microglial cell OGD/R injury though the activation of NF-κB signaling. Thus, Gm4419 appears to be a promising therapeutic target for ischemic stroke.

[Protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride-induced liver fibrosis in rats].

This experiment was aimed to discuss the protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Forty-eight male Sprague-Dawley rats were randomly divided into the blank control group (G1), model group (G2), total lignans high, middle and low dose groups (400,200, and 100 mg•kg⁻¹â€¢d⁻¹)(G3/4/5) and the glycyrrhizin positive control group (25 mg•kg⁻¹â€¢d⁻¹)(G6), n=8 in each group. The rats in blank group received normal feeding; the rats in model group, total lignans low, middle and high dose groups and glycyrrhizic group were subcutaneously in jected with 3 mL•kg⁻¹ olive oilsolution containing 40%CCl4 every two or three days for Eight weeks. During the course, the rats inblank group and model group were orally administered with 2 mL normal saline, and the rats in total lignans groups and the glycyrrhizin positive control group received corresponding doses of drugs by intragastric administration. Eight weeks later, after the the last time modeling, the rats were sacrificed. Then the biochemical analysis was used to determine alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase (ALP) levels in serum while enzyme-linked immuno sorbent assay(ELISA) was applied for detecting transforming growth factor ß1(TGF-ß1), hyaluronic acid(HA), hydroxy-proline(HYP) and superoxide dismutase(SOD) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissues to observe the pathological variations and grades of hepatic fibrosis. The results showed that as compared with the model group, the levels of ALT, AST, ALP, TGF-ß1, HA, HYP and SOD in serum of total lignans groups were significantly decreased (P<0.05, P<0.01); levels of SOD in the liver tissue homogenate were increased(P<0.05, P<0.01); the pathological damage of the liver tissues were relieved (P<0.05, P<0.01), and liver fibrosis scores were decreased(P<0.05, P<0.01). The above experimentsindicated that total lignans from Tibetan medicinal Herpetospermum seeds can effectively reduce carbon tetrachloride-induced hepatic injury of rat liver fibrosis, reduce the degree of liver fibrosis, and its mechanism maybe associated with down-regulating TGF-ß1 expression.

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

BACKGROUND: To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. METHODS: 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. RESULTS: After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). CONCLUSION: Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

Telomerase-null survivor screening identifies novel telomere recombination regulators.

Telomeres are protein-DNA structures found at the ends of linear chromosomes and are crucial for genome integrity. Telomeric DNA length is primarily maintained by the enzyme telomerase. Cells lacking telomerase will undergo senescence when telomeres become critically short. In Saccharomyces cerevisiae, a very small percentage of cells lacking telomerase can remain viable by lengthening telomeres via two distinct homologous recombination pathways. These "survivor" cells are classified as either Type I or Type II, with each class of survivor possessing distinct telomeric DNA structures and genetic requirements. To elucidate the regulatory pathways contributing to survivor generation, we knocked out the telomerase RNA gene TLC1 in 280 telomere-length-maintenance (TLM) gene mutants and examined telomere structures in post-senescent survivors. We uncovered new functional roles for 10 genes that affect the emerging ratio of Type I versus Type II survivors and 22 genes that are required for Type II survivor generation. We further verified that Pif1 helicase was required for Type I recombination and that the INO80 chromatin remodeling complex greatly affected the emerging frequency of Type I survivors. Finally, we found the Rad6-mediated ubiquitination pathway and the KEOPS complex were required for Type II recombination. Our data provide an independent line of evidence supporting the idea that these genes play important roles in telomere dynamics.

Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis.

Cathepsin B (CB) is involved in the turnover of proteins and has various roles in maintaining the normal metabolism of cells. In our recent study, CB is increased in the muscles of polymyositis/dermatomyositis (PM/DM). However, the role of CB in interstitial lung disease (ILD) has not been reported. ILD is a frequent complication of PM/DM, which is the leading cause of death in PM/DM. It carries high morbidity and mortality in connective tissue diseases, characterized by an overproduction of inflammatory cytokines and induced fibrosis, resulting in respiratory failure. The etiology and pathogenesis of ILD remain incompletely understood. This study investigated whether treatment with CA-074Me, a specific inhibitor of CB, attenuates ILD in PM. CB expression, inflammation, and fibrosis were analyzed in the lung tissues from patients with PM/DM. The animal model of PM was induced in guinea pigs with Coxsackie virus B1 (CVB1). CA-074Me was given 24 h after CVB1 injection for 7 consecutive days. At the end of the experiment, the animals were killed and lung tissues were collected for the following analysis. Inflammation, fibrosis and apoptosis cells, and cytokines were assessed by histological examinations and immunohistochemical analyses, western blot analysis and transferase-mediated dUTP nick-end labeling assay. In patients with PM/DM, the protein levels of CB were significantly elevated in lung tissues compared with healthy controls, which correlated with increases in inflammation and fibrosis. Similarly, the expression of CB, inflammation and fibrosis, CD8(+) T cell, CD68(+) cell, tumor necrosis factor-alpha, transforming growth factor-beta1 infiltrations, and apoptotic cell death were significantly increased in lung tissues of the guinea-pig model of CVB1-induced PM. These changes were attenuated by the administration of CA-074Me. In conclusion, this study demonstrates that PM/DM increases CB expression in lung tissues and inhibition of CB reduces ILD in a guinea-pig model of CVB1-induced PM. This finding suggests that CB may be a potential therapeutic target for ILD.

Activation of LXR attenuates collagen-induced arthritis via suppressing BLyS production.

B-lymphocyte stimulator (BLyS) plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Liver X receptor (LXR), a nuclear receptor, has an important anti-inflammatory effect. However, it is unclear whether the BLyS expression is regulated by LXR. In this study, we found that treatment with LXR agonist in collagen-induced arthritis (CIA) mice significantly attenuated arthritis progression, and markedly decreased BLyS production in serum and splenocytes as well as the production of serum IFNγ and TGFß. Activation of LXR in B lymphocytes dramatically suppressed the basal and IFNγ/TGFß-induced BLyS expression. Moreover, LXR agonist prominently suppressed the binding of NF-κB to BLyS promoter region, and decreased the promoter's transcriptional activity. Additionally, activation of LXR obviously repressed IFNγ-induced STAT1 activation and TGFß-induced SMAD3 activation. These results indicated that downregulation of BLyS may be a novel mechanism by which LXR ameliorates RA, and LXR/BLyS pathway may serve as a novel target for the treatment of RA.

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated. OBJECTIVES: To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tong-xin-luo capsules for at least three months. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea. AUTHORS' CONCLUSIONS: The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.

Interleukin-2 as maintenance therapy for children and adults with acute myeloid leukaemia in first complete remission.

BACKGROUND: Acute myeloid leukaemia (AML) is a malignant cancer of hematopoietic stem cells. The treatment of AML consists of two treatment phases: the remission induction phase to achieve a rapid, complete remission (CR) and the consolidation phase to achieve a durable molecular remission. People in CR are at risk of AML relapse, and people with relapsed AML have poor survival prospects. Thus, there is a continuous need for treatments to further improve prognosis. Interleukin-2 (IL-2), an immune-stimulatory cytokine, is an alternative to standard treatment for people with AML to maintain the efficacy after consolidation therapy. Maintenance therapy is not an integral part of the standard treatment for AML. Studies have been conducted to evaluate the efficacy of IL-2 as maintenance therapy for people with AML in first CR, but the effect of IL-2 is not yet fully established. OBJECTIVES: To evaluate the efficacy and safety of IL-2 as maintenance therapy for children and adults with AML who have achieved first CR and have not relapsed. SEARCH METHODS: We systematically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 8), MEDLINE (1950 to August 2015), EMBASE (1950 to August 2015), LILACS (1982 to August 2015), CBM (1978 to August 2015), relevant conference proceedings (2000 to 2015), and metaRegister of Controlled Trials (since inception to August 2015) of ongoing and unpublished trials. In addition, we screened the reference lists of relevant trials and reviews. SELECTION CRITERIA: Eligible studies were randomised controlled trials (RCTs) comparing IL-2 with no treatment in people with AML who had achieved first CR and had not relapsed. We did not identify studies comparing IL-2 versus best supportive care or maintenance chemotherapy or studies comparing IL-2 plus maintenance chemotherapy versus maintenance chemotherapy alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data with a predefined extraction form, and assessed risk of bias of included studies. We extracted data on the following outcomes: disease-free survival, overall survival, event-free survival, treatment-related mortality, adverse events, and quality of life. We measured the treatment effect on time-to-event outcomes and dichotomous outcomes with hazard ratio (HR) and risk ratio, respectively. We used inverse-variance method to combine HRs with fixed-effect model unless there was significant between-study heterogeneity. MAIN RESULTS: We included nine RCTs with a total of 1665 participants, comparing IL-2 with no treatment. Six studies included adult participants, and three studies included both adults and children. However, the latter three studies did not report data for children, thus we were unable to conduct subgroup analysis of children. One Chinese study did not report any outcomes of interest for this review. We included six trials involving 1426 participants in the meta-analysis on disease-free survival, and included five trials involving 1355 participants in the meta-analysis on overall survival. There is no evidence for difference between IL-2 group and no-treatment group regarding disease-free survival (HR 0.95; 95% CI 0.86 to 1.06, P = 0.37; quality of evidence: low) or overall survival (HR 1.05; 95% CI 0.95 to 1.16, P = 0.35; quality of evidence: moderate). Based on one trial of 161 participants, IL-2 exerted no effect on event-free survival (HR 1.02; 95% CI 0.79 to 1.32, P = 0.88; quality of evidence: low). Adverse events (including thrombocytopenia, neutropenia, malaise/fatigue, and infection/fever) were more frequent in participants receiving IL-2, according to one trial of 308 participants. No mortality due to adverse events was reported. None of the included studies reported treatment-related mortality or quality of life. AUTHORS' CONCLUSIONS: There is no evidence for a difference between IL-2 maintenance therapy and no treatment with respect to disease-free survival or overall survival of people with AML in first CR; however, the quality of the evidence is moderate or low, and further research is likely or very likely to have an important impact on the estimate or our confidence in the estimate. Adverse events seem to be more frequent in participants treated with IL-2, but the quality of the evidence is very low and our confidence in the estimates is very uncertain. Thus, further prospective randomised trials are needed before definitive conclusions can be drawn on these issues.

Histone H4 lysine 12 acetylation regulates telomeric heterochromatin plasticity in Saccharomyces cerevisiae.

Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity.

An internet-based epidemiological investigation of the outbreak of H7N9 Avian influenza A in China since early 2013.

BACKGROUND: In early 2013, a new type of avian influenza, H7N9, emerged in China. It quickly became an issue of great public concern and a widely discussed topic on the Internet. A considerable volume of relevant information was made publicly available on the Internet through various sources. OBJECTIVE: This study aimed to describe the outbreak of H7N9 in China based on data openly available on the Internet and to validate our investigation by comparing our findings with a well-conducted conventional field epidemiologic study. METHODS: We searched publicly accessible Internet data on the H7N9 outbreak primarily from government and major mass media websites in China up to February 10, 2014. Two researchers independently extracted, compared, and confirmed the information of each confirmed H7N9 case using a self-designed data extraction form. We summarized the epidemiological and clinical characteristics of confirmed H7N9 cases and compared them with those from the field study. RESULTS: According to our data updated until February 10, 2014, 334 confirmed H7N9 cases were identified. The median age was 58 years and 67.0% (219/327) were males. Cases were reported in 15 regions in China. Five family clusters were found. Of the 16.8% (56/334) of the cases with relevant data, 69.6% (39/56) reported a history of exposure to animals. Of the 1751 persons with a close contact with a confirmed case, 0.6% (11/1751) of them developed respiratory symptoms during the 7-day surveillance period. In the 97.9% (327/334) of the cases with relevant data, 21.7% (71/327) died, 20.8% (68/327) were discharged from a hospital, and 57.5% (188/327) were of uncertain status. We compared our findings before February 10, 2014 and those before December 1, 2013 with those from the conventional field study, which had the latter cutoff date of ours in data collection. Our study showed most epidemiological and clinical characteristics were similar to those in the field study, except for case fatality (71/327, 21.7% for our data before February 10; 45/138, 32.6% for our data before December 1; 47/139, 33.8% for the field study), time from illness onset to first medical care (4 days, 3 days, and 1 day), and time from illness onset to death (16.5 days, 17 days, and 21 days). CONCLUSIONS: Findings from our Internet-based investigation were similar to those from the conventional field study in most epidemiological and clinical aspects of the outbreak. Importantly, publicly available Internet data are open to any interested researchers and can thus greatly facilitate the investigation and control of such outbreaks. With improved efforts for Internet data provision, Internet-based investigation has a great potential to become a quick, economical, novel approach to investigating sudden issues of great public concern that involve a relatively small number of cases like this H7N9 outbreak.

Pneumonia in an elderly Tibetan male caused by Shewanella algae: A case report.

RATIONALE: Shewanella algae are Gram-negative bacteria that are widely found in aquatic habitats and rarely cause lung infections in inland areas. PATIENT CONCERNS: Cough with light-yellow phlegm for 2 weeks. DIAGNOSES: The final diagnosis was bacterial pneumonia. INTERVENTIONS: The patient was treated with ceftazidime (2 g, every 12 h) for 1 week. OUTCOMES: The patient's lung infection improved and he was discharged. LESSONS: This case highlights a rare occurrence of lung infection caused by Shewanella algae in elderly Tibetan men residing in non-marine environments.

Platelet Membrane-Encapsulated Nanocomplexes Based on Profundity Scavenging ROS Strategy for Myocardial Infarction Therapy.

Ischemia-induced myocardial injury has become a serious threat to human health, and its treatment remains a challenge. The occurrence of ischemic events leads to a burst release of reactive oxygen species (ROS), which triggers extensive oxidative damage and leads to dysfunctional autophagy, making it difficult for cells to maintain homeostasis. Antioxidants and modulation of autophagy have thus become promising strategies for the treatment of ischemic myocardial injury. This study proposes an antioxidant-activated autophagy therapeutic regimen based on combining melanin (Mel), an excellent antioxidant with metformin mimetic ploymetformin via electrostatic interactions, to obtain a nanocomplex (Met-Mel). The nanocomplex is finally encapsulated with platelet membranes (PMN) to construct a biomimetic nanoparticle (PMN@Met-Mel) capable of targeting injured myocardium. The prepared PMN@Met-Mel has good Mel loading capacity and optimal biosafety. It exhibits excellent antioxidant activity and autophagy activation, rapidly restoring mitochondrial function. Moreover, RNA sequencing (RNA-seq) analysis reveals that PMN@Met-Mel operates mechanistically by triggering the activation of the autophagy pathway. Subsequent in vivo experiments showcase promising cardioprotective effects of these nanoparticles. These discoveries present a newly devised nanoplatform with promising potential for the effective treatment of myocardial infarction.