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Chlorophyll-a concentration (chl-a) is a great indicator for estimating phytoplankton biomass and productivity levels and is also particularly useful for monitoring the water quality, biodiversity and species distribution, and harmful algal blooms. A great deal of studies investigated to estimate chl-a concentrations using ocean color remotely sensed data. With the development of photon-counting sensors, spaceborne photon-counting lidar can compensate for the shortcomings of passive optical remote sensing by enabling ocean vertical profiling in low-light conditions (e.g., at night). Using geolocated photons captured by the first spaceborne photon-counting lidar borne on ICESat-2 (Ice, Cloud, and Land Elevation Satellite-2), this research reported methods for deriving vertical profiles of chl-a concentration in the upper layer of ocean waters. This study first calculates the average numbers of backscattered subaqueous photons of ICESat-2 at different water depths, and then estimates the optical parameters in water column based on a discrete theoretical model of the expected number of received signal photons. With the estimated optical parameters, vertical profiles of chl-a concentration are calculated by two different empirical algorithms. In two study areas (mostly with Type I open ocean waters and small part of Type II coastal ocean waters), the derived chl-a concentrations are generally consistent when validated by BGC-Argo (Biogeochemical Argo) data in the vertical direction (MAPEs2>0.86). Using globally covered ICESat-2 data, this approach can be used to obtain vertical profiles of chl-a concentration and optical parameters at a larger scale, which will be helpful to analyze impact factors of climate change and human activities on subsurface phytoplankton species and their growth state.

Background: Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota and other clinical outcomes in critically ill patients, the results from different studies were not consistent. Objective: The purpose of this study was to explore the effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation and clinical outcomes in critically ill patients. Methods: A search was performed through PubMed, Embase, the Cochrane Central Register of Clinical Trials, Web of Science and EBSCO-host that includes Health Sciences Research from inception to July 12, 2021. Data were pooled using fixed effects model for low heterogeneity and random effects model for high heterogeneity. Data were expressed as mean difference (MD) or odds ratio (OR) with confidence interval. Results: A total of 21 studies involving 2084 critically ill patients were included. The results showed that there was a significant reduction in intestinal permeability demonstrated by lactulose/rhamnose ratio (MD:-0.04; 95%CI:-0.08, -0.00; P=0.03) on day 8 in DF supplement group. Three studies reported the relative abundance (RA) of gut microbiota and the results showed the RA of some SCFAs producers increased higher in DF supplement group. There was a significant decrease in C-reactive protein on day 14 (MD:-36.66; 95%CI:-44.40, - 28.93; P

Percutaneous nephrolithotomy (PCNL) is the first-line and guideline-recommended treatment for large renal calculi. Multimodal analgesia (MMA) comprising a combination of different analgesics is an increasingly popular method for pain control as it has been shown to reduce postoperative pain and reduce opioid use and the risk of opioid misuse, with a shorter recovery time in various procedures and patient populations.In this study, we tested the hypothesis that MMA with propofol and sevoflurane (PS) can decrease pain intensity during surgery and used IoC2 as a real-time index of the analgesic effect of sevoflurane.Prospective, single-center, double-blind, randomized controlled clinical trial.Xuanwu Hospital of Capital Medical University.Patients scheduled for elective percutaneous nephrolithotomy from January 2020 to July 2020 were randomized into 2 groups, standard multimodal analgesia (propofol + sevoflurane group) and control (propofol [P] group). The PS group received propofol 2.5 mg/kg/h along with 1% sevoflurane after induction for 30 minutes during the main anesthetic procedure, and the P group received propofol 5 mg/kg/h by intravenous infusion during the operation. Index of consciousness 2 (IoC2), namely nociception index, intraoperative hemodynamic fluctuation, bispectral index (BIS), electromyography, postanesthesia care unit (PACU) length of stay, visual analog scale (VAS) score, and Aldrete and Steward scores were recorded.A total of 153 patients undergoing PCNL were enrolled. The demographic and clinical characteristics were similar between the 2 groups. IoC2 was reduced in the PS group compared to the P group at T10, T11, T12, T13, T14, and T15 time points, indicating that analgesia was more effective in the former. The BIS of the PS group did not differ significantly from that of the P group except at T12, T13, T14, and T15. PACU length of stay was shorter in the PS group than in the P group (mean [SD]: 54.35 [16.61] vs 47.39 [13.15], P = 0.04). VAS pain scores did not differ significantly between the 2 groups.MMA with propofol and sevoflurane provided better analgesia than propofol alone and may be an effective method to reduce stress and the intraoperative nociceptive stimulus response in patients undergoing PCNL, thereby promoting rapid postoperative recovery.

Background To explore the risk factors and prognostic factors related to the acute-on-chronic liver failure (ACLF) occurrence and adverse outcome after withdrawal of nucleos(t)ide analogs (NAs) in chronic hepatitis B (CHB) patients. Methods Hospitalized CHB patients with relapse after NAs withdrawal at our medical center were retrospectively included in the present study from January 2011 to May 2018. Logistic regression, Cox regression analysis, Kaplan-Meier log-rank test, and area under the receiver operating characteristic curves (AUROC) were used. Results A total of 389 CHB patients (including 46 ACLF patients) were included. Their median age was 48.0 years; 315 patients were male and 74 were female. The age ≥30 years and HBVDNA ≤1000 copies at admission in logistic regression were the independent risk factors for ACLF after NAs withdrawal in CHB patients. In patients who developed ACLF, only the model of end-stage liver disease combining serum natrium concentration (MELD-Na) score and relapse after Lamivudine (LAM) cessation in the Cox multivariate regression analysis were independent predictors for 12-week mortality. The artificial liver support system (ALSS) showed no improvement in the 12-week survival of ACLF patients. We further defined 22.35 as the optimal cutoff value of MELD-Na score to predict 12-week mortality for ACLF patients, with the AUROC of 0.817, a sensitivity of 76.5%, and a specificity of 75.9%. Conclusion The age ≥30 years and HBVDNA ≤1000 copies at admission strongly correlate with occurrence of ACLF, and higher MELD-Na score and relapse after LAM withdrawal are closely related with 12-week mortality among patients with ACLF after NAs withdrawal.

We conducted a meta-analysis to systematic assess the diagnostic value of computed tomography (CT)-based pulmonary artery to aorta (PA:A) ratio measurement in COPD with pulmonary hypertension (COPD-PH).Published studies referring to diagnostic accuracy of PA:A ratio for COPD-PH were screened out from PubMed, Embase, Web of science, China National Knowledge databases (CNKI), Wan fang databases, and VIP databases. We used bivariate random-effects model to estimate pooled sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR, respectively), and diagnostic odds ratios (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were also calculated to summarize the aggregate diagnostic performance.Nine eligible studies were included and the pooled SEN was 69% (95% CI: 59 ~ 78), SPE was 85% (95% CI: 77 ~ 90), PLR was 4.5 (95% CI: 2.8 ~ 7.5), and NLR was 0.36 (95% CI: 0.26 ~ 0.51), respectively. DOR reached 13.00 (95% CI: 6.00 ~ 28.00), and value of AUC was 0.84 (95% CI: 0.81 ~ 0.87). Subgroup analysis indicated that when the value of PA:A ratio was equal or greater than one (PA/A ≥ 1), the combined SEN, SPE, AUC, and DOR was 69%, 89%, 0.90, and 19.65, respectively.PA:A ratio is helpful for appraisal of COPD-PH, and PA/A ≥ 1 possessed prominent diagnostic accuracy.

Although some studies have explored the relationships between dietary fibre and enteral feeding intolerance in critically ill patients, the results are equivocal.This study aimed to explore the effects of dietary fibre on enteral feeding intolerance and clinical outcomes in critically ill patients.We searched five databases from inception to July 12, 2021. Data were expressed as mean difference or odds ratio with 95% confidence interval.Thirteen studies enrolled 709 critically ill patients included in the study. The results showed the dietary fibre group had a significantly decreased risk of diarrhea (OR: 0.46, 95% CI: 0.30,0.69, P 0.001), regurgitation (OR: 0.28, 95%CI: 0.13, 0.60, P 0.05), vomiting (OR: 0.40, 95%CI: 0.17, 0.92, P 0.05), constipation (OR: 0.21, 95%CI: 0.09, 0.47, P 0.001) and mortality (OR:0.34; 95%CI:-0.13, 0.91; P 0.05) compared with the fibre free group. Besides, there was a significant decrease on time to reach full enteral nutrition (MD:-2.08; 95%CI:-4.05, -0.12; P 0.05), the duration of the intensive care unit stay (MD:-4.62; 95%CI:-6.60, -2.64; P 0.001) and hospital stay (MD:-6.42; 95%CI:-9.49, -3.36; P 0.001) in the dietary fibre group.Dietary fibre supplementation may significantly reduce the risk of enteral feeding intolerance and improve the clinical outcomes.

Secukinumab, a full human immunoglobulinG1κ(IgG1κ) monoclonal antibody that targets interleukin-17A, has demonstrated remarkable efficacy and appreciable tolerance in patients with moderate-to-severe psoriasis. However, data on its real-life performance, particularly on drug survival in China are limited. To investigate the efficacy, safety, and drug survival of secukinumab in Chinese patients with psoriasis, we conducted a monocentric retrospective study of 66 patients with moderate-to-severe psoriasis to followed-up for 52 weeks. At week 12, 86.4%, 57.6%, and 10.6% of the patients attained 75% improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 75), PASI 90, and PASI 100 responses, respectively. The quality of life of patients markedly improved. The overall survival rate was 74.2%. Adverse events (AEs) occurred in 30 patients (45.5%). The results revealed favorable efficacy, safety, and tolerability of secukinumab in the treatment of patients with psoriasis and provided data on drug survival in real-life clinical setting in China for the first time. This article is protected by copyright. All rights reserved.

Real-life data on guselkumab in psoriasis are limited and not available in China hitherto. This study aimed to evaluate the short-term effectiveness and safety of guselkumab in patients with psoriasis under Chinese real-life conditions and to explore the effect of guselkumab on CD4+ CD25+ Foxp3+ regulatory T cells (Tregs). A Chinese prospective and real-life study involving patients with psoriasis in Dermatology Hospital of Southern Medical University, Guangzhou, China from April to September 2020 was conducted. A total of 45 patients with psoriasis were finally enrolled in the study. Psoriasis Area Severity Index (PASI) 90 and 100 responses at week 16 were achieved by 88.6% and 45.5% of patients, respectively. The analysis of PASI response in different subgroups showed no statistically significant difference. Univariate logistic regression analysis revealed that at week 16, none of the variables were associated with decreasing PASI 90 response, whereas age at onset of disease was a predictor of PASI 100 response. Dynamic detection of CD4+ CD25+ Foxp3+ Tregs frequency from peripheral blood suggested a stable maintained trend in terms of guselkumab treatment duration. No severe adverse events occurred during the follow-up period. This study confirmed the short-term effectiveness and safety of guselkumab, as well as its good tolerance against psoriasis, in the Chinese population. Guselkumab treatment maintains levels of Tregs in patients with psoriasis.

Nucleophosmin (NPM)/B23 is an important nucleolar phosphoprotein involved in the regulation of assorted cellular signaling pathways. In the present study, we revealed a critical role of NPM in liver insulin resistance. NPM is markedly upregulated in insulin-resistant liver tissues and palmitic acid (PA)-exposed HepG2 cells both at mRNA and protein levels. Ectopic expression of NPM in hepatocytes aggravated PA-induced insulin resistance, lipid droplet accumulation, glucose intake impairment as well as the expression of gluconeogenic genes. Coinciding with these results, interference of NPM using small interfering RNA (siRNA) oligos ameliorated PA-induced insulin resistance, as revealed by increased phosphorylation of AKT and GSK3β following insulin treatment. As predicted, PA-triggered alterations in glucose intake and the expression of gluconeogenic enzymes were attenuated following NPM depletion. Finally, we showed that NPM plays an indispensible role in PA-induced activation of NF-κB pathway. Both of NF-κB p65 phosphorylation and nuclear translocation were impeded by NPM interference in PA-treated HepG2 cells. Taken together, these findings explicitly demonstrate that NPM participates in the development of liver insulin resistance, suggesting that NPM may serve as a potential therapeutic target of type 2 diabetes.

Background Patients with coronary heart disease (CHD) often experience anxiety, but the current studies on anxiety mostly focused on a certain point in time. Therefore, this study aimed to investigate the dynamic changes of peri-procedure anxiety, status of post-procedure quality of life, and cardiovascular readmission rates in patients with CHD who undergoing elective percutaneous coronary intervention (PCI), and to analyze the influence of peri-procedure anxiety on quality of life and readmission rate after PCI. Methods This prospective study was conducted at Changshu NO.1 People’s Hospital. A total of 220 patients with CHD undergoing elective PCI were selected as study subjects. The general information, clinical data, anxiety, quality of life and readmission of patients were collected. Multivariate linear regression was used to examine the effect of peri-procedure anxiety on quality of life, and multivariate logistic regression was used to analyze the influence of peri-procedure anxiety on readmission rate. Results This study showed the anxiety scores at hospitalization appointment(T1), 3 days before procedure(T2), 1 day before procedure(T3), 1 day after procedure(T4) were 57(55,61),64(61,68),54(51.58), and 54(50,60), respectively. And, at 3 months and 6 months after PCI, the scores of Seattle Angina Questionnaire (SAQ) were 346.61(319.06,366.52) and 353.34(334.18,372.84) respectively. During 6 months follow-up, 54 cases were readmitted, with a readmission rate of 25.5%. Statistical analysis showed that T1 with anxiety (P = 0.002) and T2 with anxiety (P = 0.024) were independent risk factors for treatment satisfaction at 3 months after PCI. Anxiety in T4 (P = 0.005) was an independent risk factor on the angina frequency at 6 months after PCI. T2 with anxiety (B = 1.445, P = 0.010, 95%CI:1.409–12.773) and T4 without anxiety (B = -1.587, P = 0.042, 95%CI:-0.044–0.941) were risk factors affecting readmission for cardiovascular reasons within 6 months. Conclusion Patient anxiety at T1 and T2 affects the treatment satisfaction dimension of the SAQ at 3 months after PCI, and anxiety at T4 affects the angina frequency dimension of the SAQ at 6 months after PCI. Anxiety at T2 and no anxiety at T4 increase short-term readmission rates. In the future, interventions should be strengthened at various time points in the peri-procedure period to improve post-procedure rehabilitation effect.

To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML).A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. The risk stratification of patients was poor or very poor, according to IPSS-R score. The treament results of decitabine combined with CEG and decitabine combined with CAG were compared.The comparison of the two regiem showed that the DCEG regimen had advantages on total effective rate (ORR, 86.4% vs 47.8%, respectively), overall survival time (OS) (10.0 months vs 6.0 months, respectively) and progression-free survival time (PFS) (9.0 months vs 3.0 months, respectively). About 50% of MDS patients treated by DCEG regimen achieved PR or CR, with a median OS of 31 months. Multivariate analysis showed that patients with PR or CR after induction therapy and DCEG regimen had longer survival time (31months). The incidence of bone marrow suppression, infection and treatment-related mortality rate were similar between the two groups.Decitabine combined with CEG regimen could improve the survival of patients with high-risk MDS and MDS-transformed AML. The conclusion of the reaserch needs to be validated by a larger prospective randomized clinical trial.地西他滨联合低剂量CEG方案与地西他滨联合低剂量CAG方案治疗老年高危MDS和MDS转化的AML患者的疗效比较.评估地西他滨联合低剂量CEG方案（DCEG）与地西他滨联合低剂量CAG方案（DCAG）治疗老年MDS和MDS转化的急性髓系白血病（AML）患者的疗效。.在7个医疗中心开展前瞻性研究, 选取2016年10月至2019年1月年龄≥60岁的MDS和MDS转化的AML患者共45例, 中位年龄68.5岁。按照IPSS-R评分, 患者危险度分层均为高危或者极高危。将地西他滨联合CEG方案与地西他滨联合CAG方案的治疗结果进行比较。.DCEG与DCAG组比较结果显示, 总有效率（ORR, 86.4% vs 47.8%）、总生存时间（OS, 10 vs 6个月）和无进展生存时间（PFS, 9 vs 3个月）, DCEG均显示有优势（P＜0.05）。在MDS患者中, DCEG组患者50%取得了PR或PR以上的疗效, 中位OS时间长达31个月。多因素分析显示, 经诱导治疗达PR或以上以及应用DCEG方案患者具有更长的生存时间。2组的骨髓抑制和感染的发生率、治疗相关死亡率相似。.与DCAG方案相比, DCEG方案可以改善高危MDS和MDS转AML患者的生存。这一结论需要更大规模的前瞻性随机临床研究来验证。.

International audience; The impacts of microplastics (MPs) and phthalates (PAEs), a class of MP-associated contaminants, on the marine environment are not thoroughly understood despite concern over their adverse effects on humans and ecosystems. Field studies linking MPs and PAEs in seawater have not yet been reported. We investigate for the first time the correlation between MPs contamination and the presence of PAEs in the surface seawater of Jiaozhou Bay (JZB), a semi-enclosed metropolitan bay in northern China heavily impacted by human activity. The abundance of MPs, dominated by polyethylene and polyethylene terephthalate mostly smaller than 2 mm, ranged between 24.44 items/m3 and 180.23 items/m3, with the majority being black and transparent fibers and fragments. Concentrations of PAEs varied from 129.96 ng/L to 921.22 ng/L. Relatively higher abundances of MPs and higher concentrations of PAEs were generally found in areas near riverine inputs and sewage treatment plants. There was a strong correlation between PAEs concentration and MPs abundance, suggesting that they are closely linked. In a risk assessment combining PAEs and MPs, the risk quotients (RQs) indicated that the ecological risk of di-n-butyl phthalate in JZB was relatively high (0.046

Oxidative stress from the trophoblasts is one of the possible pathological mechanisms of Preeclampsia (PE). This study aimed at exploring the potential effects of astaxanthin (ATX) on oxidative stress damaged placental trophoblast cell line HTR-8/SVneo. Oxidative stress-induced damaged through H

Type 2 diabetes (T2D) is characterized by islet β-cell dysfunction and impaired suppression of glucagon secretion of α-cells in response to oral hyperglycaemia. Bile acid (BA) metabolism plays a dominant role in maintaining glucose homeostasis. So we evaluated the association of fasting serum total bile acids (S-TBAs) with insulin sensitivity, islet β-cell function and glucagon levels in T2D. Total 2,952 T2D patients with fasting S-TBAs in the normal range were recruited and received oral glucose tolerance tests for determination of fasting and postchallenge glucose, C-peptide and glucagon. Fasting and systemic insulin sensitivity were assessed by homeostasis model assessment (HOMA) and Matsuda index using C-peptide, i.e., ISHOMA-cp and ISIM-cp, respectively. Islet β-cell function was assessed by the insulin-secretion-sensitivity-index-2 using C-peptide (ISSI2cp). The area under the glucagon curve (AUCgla) was used to assess postchallenge glucagon. The results showed ISHOMA-cp, ISIM-cp and ISSI2cp decreased, while AUCgla notably increased, across ascending quartiles of S-TBAs but not fasting glucagon. Moreover, S-TBAs were inversely correlated with ISHOMA-cp, ISIM-cp and ISSI2cp (r = -0.21, -0.15 and -‍0.25, respectively, p < 0.001) and positively correlated with AUCgla (r = 0.32, p < 0.001) but not with fasting glucagon (r = 0.033, p = 0.070). Furthermore, after adjusting for other clinical covariates by multiple linear regression analyses, the S-TBAs were independently associated with ISHOMA-cp (β = -0.04, t = -2.82, p = 0.005), ISIM-cp (β = -0.11, t = -7.05, p < 0.001), ISSI2cp (β = -0.15, t = -10.26, p < 0.001) and AUCgla (β = 0.29, t = 19.08, p < 0.001). Increased fasting S-TBAs are associated with blunted fasting and systemic insulin sensitivity, impaired islet β-cell function and increased glucagon levels in response to glucose challenge in T2D.

Objective Numerous studies suggested autophagy was involved in temozolomide (TMZ) resistance in glioma. Long non-coding RNA (lncRNA) CASC2 was shown to be downregulated in glioma tissues and cell lines, and was related to the TMZ resistance. However, whether CASC2 affects TMZ resistance through regulating autophagy is unknown. The aim of this study was to assess the role and mechanism of CASC2 in TMZ-induced drug resistance in glioma cells. Methods Glioma and the adjacent non-cancerous tissues from 32 patients were collected. The expressions of CASC2 and miR-193a-5p were determined by PCR, and their correlation was analyzed. The correlation between CASC2 expression and the clinical characteristics of patients was also studied. Glioma cells were treated with TMZ to acquire the TMZ-resistant cell lines in which the expressions of CASC2, miR-193a-5p, and mTOR were measured. The regulatory roles of CASC2, miR-193a-5p, and mTOR were defined through the loss of function and luciferase reporter assays. Autophagy was inhibited by autophagy inhibitor 3-MA, CASC2 and mTOR overexpression, or miR-193a-5p inhibitor, and the effect of which on cell viability, apoptosis, and migration of TMZ-resistant glioma cells was evaluated. Results CASC2 downregulation and miR-193a-5p upregulation was found to be associated with advanced clinical stage and TMZ response in patients with glioma. CASC2 negatively regulates miR-193a-5p expression by direct interaction in glioma cells. Overexpression of CASC2 or inhibition of miR-193a-5p reduced TMZ-induced autophagy via mTOR upregulation, which makes the glioma cells become sensitive to TMZ cytotoxicity. Conclusion CASC2 is downregulated in gliomas, resulting in increased miR-193a-5p level and a decrease in mTOR expression, which further induces protective autophagy, leading to TMZ resistance. Inhibition of autophagy helps to increase the efficacy of TMZ.

Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infancy, which is a major risk factor for recurrent wheezing and asthma. Orosomucoid 1-like protein 3 (ORMDL3) has been reported to associate with virus-triggered recurrent wheezing and asthma in children. However, little is known about how ORMDL3 is involved into RSV infection. In this study, we showed that the mRNA expression of ORMDL3 is significantly increased in the peripheral blood lymphocytes of infants with RSV-induced bronchiolitis compared with uninfected controls, also increased in bronchial epithelial cells and lung fibroblasts following RSV infection in vitro. To investigate the underlying mechanisms of RSV-induced ORMDL3 expression, we performed in silico analysis of the binding sites of several transcription factors in the ORMDL3 promoter. The proximal interferon-regulatory factor-3 (IRF-3) binding site positively regulated ORMDL3 transcription following exposure to RSV, as determined through mutational analysis. Overexpression and RNA interference experiments targeting IRF-3 showed that it regulates the expression of ORMDL3 following RSV exposure. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay showed that IRF-3 binds directly to the promoter of the ORMDL3 gene. Furthermore, we confirmed that expression of IRF-3 is significantly increased and shows a strong linear correlation with increased ORMDL3 in the peripheral blood lymphocytes from infants with RSV-induced bronchiolitis. Our results indicate that IRF-3 is an important regulator of ORMDL3 induction following RSV infection by binding directly to the promoter of ORMDL3, which may be implicated in the inflammatory and immune reactions involved in bronchiolitis and wheezing diseases.

Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM. Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1–3 intravenously. After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients

Backgrounds Our lab focused on the structural and functional properties of Pin1, which is the only known cis – trans isomerase regulating pSer/pThr–Pro motifs in proteins and facilitates various signaling pathways. We are lucky enough to read the article, contributed by Costantino et al. in your esteemed journal, on the role of Pin1 in diabetes-induced vascular dysfunction. Pin1 regulates the production of nitric oxide (NO), which is a key physiological stimulator of blood vessels and promotes vascular relaxation responses significantly. However, the regulation of cardiovascular diseases by Pin1 is somewhat controversial. Methods and results We compared the recent studies that support the down-regulation, as well as up-regulation, of NO production by Pin1 and tried to explore the underlying molecular mechanisms. We especially compared the different regulations of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) by Pin1, which is potentially the major reason leading to the controversial role of Pin1. Interestingly, the regulation of both eNOS and iNOS by Pin1 involves a double-edge effect, positively and negatively, contributing to paradoxical Pin1 functions in different animal models and cell lines. The extremely complex Pin1-regulated signaling networks might further exacerbate distinct cellular responses in vivo and influence NO production. Conclusions Pin1 plays a dual role, both positive and negative, in regulating NO production and in mediating the pathogenesis of cardiovascular diseases. Pin1 functions may vary a lot under different circumstances. Future investigations should focus on eNOS as well as iNOS in order to increase authenticity and accuracy of results.

The COVID-19 pandemic might lead to more mental health problems. However, few studies have examined sleep problems, depression, and posttraumatic symptoms among the general adult population during the COVID-19 outbreak, and little is known about coping behaviors. This survey was conducted online in China from February 1st to February 10th, 2020. Quota sampling was used to recruit 2993 Chinese citizens aged &ge, 18 years old. Mental health problems were assessed with the Post-Traumatic Stress Disorders (PTSD) Checklist for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the Center for Epidemiological Studies Depression inventory, and the Pittsburgh Sleep Quality Index. Exposure to COVID-19 was measured with questions about residence at outbreak, personal exposure, media exposure, and impact on livelihood. General coping style was measured by the brief Coping Style Questionnaire (SCSQ). Respondents were also asked 12 additional questions about COVID-19 specific coping behaviors. Direct exposure to COVID-19 instead of the specific location of (temporary) residence within or outside the epicenter (Wuhan) of the pandemic seems important (standardized beta: 0.05, 95% confidence interval (CI): 0.02&ndash, 0.09). Less mental health problems were also associated with less intense exposure through the media (standardized beta: &minus, 0.07, 95% CI: &minus, 0.10&ndash, &minus, 0.03). Perceived negative impact of the pandemic on livelihood showed a large effect size in predicting mental health problems (standardized beta: 0.15, 95% CI: 0.10&ndash, 0.19). More use of cognitive and prosocial coping behaviors were associated with less mental health problems (standardized beta: &minus, 0.30, 95% CI: &minus, 0.34&ndash, 0.27). Our study suggests that the mental health consequences of the lockdown impact on livelihood should not be underestimated. Building on cognitive coping behaviors reappraisal or cognitive behavioral treatments may be most promising.

Herpes simplex virus type 1 (HSV-1) is the most common virus, with an estimated infection rate of 60–95% among the adult population. Once infected, HSV-1 can remain latent in the host for a lifetime and be reactivated in patients with a compromised immune system. Reactivation of latent HSV-1 can also be achieved by other stimuli. Though acyclovir (ACV) is a classic drug for HSV-1 infection, ACV-resistant strains have been found in immune-compromised patients and drug toxicity has also been commonly reported. Therefore, there is an urge to search for new anti-HSV-1 agents. Natural products with potential anti-HSV-1 activity have the advantages of minimal side effects, reduced toxicity, and they exert their effect by various mechanisms. This paper will not only provide a reference for the safe dose of these agents if they are to be used in humans, referring to the interrelated data obtained from in vitro experiments, but also introduce the main pharmacodynamic mechanisms of traditional Chinese medicine (TCM) against HSV-1. Taken together, TCM functions as a potential source for HSV-1 therapy by direct (blocking viral attachment/absorption/penetration/replication) or indirect (reducing the susceptibility to HSV-1 or regulating autophagy) antiviral activities. The potential of these active components in the development of anti-HSV-1 drugs will also be described.

Chronic fluid over-hydration is common in dialysis patients. It is associated with mortality and cardiovascular events. Optimal methods for adjusting fluid volume status and ideal dry weight remain uncertain. The purpose of this study was to evaluate the usefulness of ultrasound in quantifying body water. In 35 hemodialysis patients, we performed ultrasound of the chest, pre-tibial skin tissue thickness (TT), heart and inferior vena cava (IVC) before and after dialysis. We compared B-line scores of lungs, IVC diameters and cardiac functions in pre-dialysis and post-dialysis groups. We then estimated the correlations between ultrasound parameters and ultrafiltration volumes. Ultrafiltration parameters were adjusted prospectively for subsequent dialysis. As a result, both extravascular and intravascular water decreased during ultrafiltration. The median numbers of B-line scores (10 [0-42] vs. 4 [0-30]; p0.001); mitral valve blood flow velocities E (0.83 ± 0.23 m/s vs. 0.70 ± 0.20 m/s; p0.001), A (0.93 ± 0.28 vs. 0.89 ± 0.23 m/s; p0.001) and E/e' (12.47 ± 4.92 vs. 10.37 ± 4.0; p0.001); IVC diameters at end-expiration (17.51 ± 3.33 mm vs. 14.26 ± 3.45 mm; p0.001); and right pre-tibial TT (2.86 ± 1.36 mm vs. 2.43 ± 1.24 mm; p0.001) decreased during dialysis. Ultrafiltration volume was most associated with B-line score (adjusting for age and sex) (β = -3.340; p = 0.003). In addition, the B-line score after dialysis was significantly associated with left ventricular ejection fraction (r = -0.393; p = 0.019) and TT (r = -0.447; p = 0.007). Ultrafiltration volume was prospectively increased then if the B-line score was6 in the previous dialysis. All patients tolerated the protocol well without any symptoms. Ultrafiltration volume was most associated with lung water, reflected by variation in B-line score. It was not associated with cardiac function, IVC diameter, IVC collapse rate or TT. Lung ultrasound is a useful imaging tool for dialysis patients.

Postoperative pain from male circumcision (MC) is common especially in the sleep-related erection period. This study aims to explore the effect of interrupted rapid eye movement (IREM) sleep on relieving SRE-related incision pain and the improvement of other clinical outcomes.This simple randomized controlled study was conducted between May and November 2016. Approval was obtained from the local ethical committee on 5 May 2016. Ninety participants who underwent male circumcision were divided into the interrupted rapid eye movement sleep group and the control group. The times and the cumulative time of erection-related moderate and severe pain in minutes at night for 3 days after the operation were observed and compared. We also compared the condition of the incision swelling and healing.Sleep time at night was used to evaluate the safety of interrupted rapid eye movement sleep.For the first 3 days after the operation, the times of sleep-related erection pain were significantly decreased in the IREM sleep group (P = .010). Five patients reported that there was no pain during night. The cumulative time of erection-related moderate and severe pain was statistically decreased in the interrupted rapid eye movement sleep group (P = .034). After 3 days, there was no moderate and severe pain related to sleep-related erection in the 2 groups. There were no significant differences in incision swelling (P = .768), healing (P = .626), and sleep time (P = .231).Interrupted rapid eye movement sleep is an effective, simple, and free treatment to relieve incision pain of sleep-related erections.

Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β). Furthermore, PKM2 overexpression enhanced the effects of PA on the lipid accumulation, the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and hepatic glucose uptake. Intriguingly, PA-induced insulin resistance was suppressed following by the ablation of PKM2 in HepG2 cells. We also found that STAT3 was significantly activated by PKM2 overexpression. Moreover, we identified that PKM2 could interact directly with STAT3. Taken together, these studies demonstrate that PKM2 may promote hepatic IR via STAT3 pathway and would provide a new insight into dissecting the molecular pathogenesis of hepatic insulin resistance.

Interferon regulatory factor 3 (IRF-3) is widely known for its prompt response against viral infection by activating the interferon system. We previously reported that E2F1, Sp1 and Sp3 regulated transcriptional activity of IRF-3. Recently, different expression patterns of IRF-3 were found in lung cancer, leading to the alternation of the immunomodulatory function in tumorigenesis. However, the mechanism of transcriptional regulation of IRF-3 in lung cancer has not been extensively studied. Here, we investigated the characterization of IRF-3 promoter and found that GATA-1 bound to a specific domain of IRF-3 promoter in vitro and in vivo. We found elevated IRF-3 and decreased GATA-1 gene expression in lung adenocarcinoma in Oncomine database. Additionally, higher IRF-3 gene expression was observed in human lung adenocarcinoma, accompanied by aberrant GATA-1 protein expression. We further analyzed the relationship of GATA-1 and IRF-3 expression in lung adenocarcinoma cell lines and found that inhibition of GATA-1 by siRNA increased the promoter activity, mRNA and protein levels of IRF-3, while over-expression of GATA-1 down-regulated IRF-3 gene expression. Taken together, we conclude that reduced GATA-1 could be responsible for the upregulation of IRF-3 in lung adenocarcinoma cells through binding with a specific domain of IRF-3 promoter.

Purpose: Cisplatin-based neoadjuvant chemotherapy (NAC) has been shown to improve survival in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy as compared with patients who underwent surgery alone. It has also been suggested as current standard of care in surgically-fit patients with MIBC. This meta-analysis assessed the effect of cisplatin-based NAC on survival in patients with bladder cancer. Source: PubMed, CENTRAL, and Embase were searched until November 22, 2016. Two-arm randomized controlled trials that compared cisplatin-based neoadjuvant chemotherapy plus local treatment versus the same local treatment without neoadjuvant chemotherapy were selected. Patients with histologically-confirmed bladder cancer (adenocarcinoma, transitional, or squamous-cell carcinoma) were included. The primary outcome was overall survival (OS). Principal findings: Of the 292 articles initially identified, 14 were included in the final analysis. Patients in the NAC group had similar OS as the local treatment (i.e., radiation therapy or cystectomy) group (pooled hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.84 to 1.00, P=0.056). No difference in progress-free survival between two groups was observed (P=0.725). Subgroup analysis showed that OS was similar in patients treated with NAC plus radiotherapy or cystectomy compared with patients who received local treatment alone. Conclusions: Platinum-based NAC was associated with similar survival benefit as patients undergoing cystectomy and/or radiotherapy. No conclusion can be drawn about the optimal platinum-based combination to be used in the neoadjuvant setting.

OBJECTIVE: To establish the diagnostic criteria for polypoidal choroidal vasculopathy (PCV) based on spectral-domain optical coherence tomography (SD OCT) by evaluating the sensitivity and specificity of SD OCT in differentiating PCV from wet age-related macular degeneration (wAMD). METHODS: The clinical data were reviewed for 62 patients (63 eyes) with the initial diagnosis of PCV or wAMD between August, 2012 and June, 2016. Twenty-four patients (25 eyes) were diagnosed to have PCV and 38 (38 eyes) had wAMD based on findings by fundus photography, fluorescein angiography (FFA) and indocyanine green angiography (ICGA). Among the 6 features of SD OCT, namely a sharp RPED peak, double-layer sign, multiple RPED, an RPED notch, a hyporeflective lumen representing polyps, and hyperreflective intraretinal hard exudates, findings of the first two features and at least one of the other features sufficed the diagnosis of PCV; in the absence of the first two features, the diagnosis of PCV was also made when at least 3 of the other features were present simultaneously. The sensitivity and specificity of SD OCT-based diagnosis were estimated by comparison with the gold standard ICGA-based diagnosis. RESULTS: In the 25 eyes with an established diagnosis of PCV, 23 eyes (92.0%) met the diagnostic criteria based on SD OCT findings; in the 38 eyes with the diagnosis of wAMD, only 4 eyes (10.5%) met the criteria. The sensitivity and specificity of SD OCT-based diagnosis of PCV was 92.0% and 89.5%, respectively. CONCLUSION: s We established the diagnostic criteria for PCV based on SD OCT findings with a high sensitivity and specificity. SD OCT shows a strong capacity for differentiating PCV from wAMD.

Although the molecular mechanism has not yet been clarified until now, it is very interesting that Alzheimer's disease (AD), hypertension (HTN), and cerebral amyloid angiopathy (CAA) often occur synchronously and possess many similar pathological characteristics. Herein, we hypothesize that a feedback signaling loop, consisted of Pin1, endothelial nitric oxide synthase (eNOS), and amyloid-β (Aβ), may contribute to the interesting pathological phenomenon. First, Pin1 inhibits the production of Aβ, and enhances the activity of eNOS. Second, Aβ and eNOS form a mutual inhibition system. Third, the well-balanced feedback signaling loop avoids the development of AD, HTN, and CAA by inhibiting the frequent pathological characteristics of these diseases, including Aβ deposition in cerebral microvessels and cerebral microbleeds. On one hand, Pin1 and eNOS not only inhibit Aβ production but also accelerate Aβ clearance, preventing Aβ deposition in cerebral microvessels. On the other hand, Pin1 and eNOS promote vasodilatation and prevent the elevation of blood pressure in brain, alleviating the pathology of cerebral microbleeds. However, once the precise balance is disturbed, it may result in Aβ deposition, microbleeds, and elevated blood pressure, possibly leading to the synchronous occurrence of AD, HTN, and CAA. The hypothesis updates the current understanding of the molecular linkage among AD, HTN, and CAA, and lays the ground for developing combined prevention, diagnosis, and treatment of these diseases more efficiently and more economically. Interestingly, biotechnical medicines enhancing the activity of Pin1 and/or eNOS may prevent the development of AD, HTN, and CAA, and targeting Aβ deposition may alleviate the clinical pathologies of these related diseases.

Fifty-two polysaccharides were isolated from the fermentation systems of Tuber melanosporum, Tuber indicum, Tuber sinense, Tuber aestivum and the fruiting bodies of Tuber indicum, Tuber himalayense, Tuber sinense by elution with an activated carbon column. Polysaccharides from Tuber fermentation system exhibited relatively higher in vitro antitumor activity against HepG2, A549, HCT-116, SK-BR-3, and HL-60 cells than those from Tuber fruiting bodies. All polysaccharides were mainly composed of D-mannose, D-glucose, and D-galactose, which suggested that the polysaccharides from Tuber fruiting bodies and fermentation system have identical chemical compositions. The results of antitumor activity and structural identification indicated that the polysaccharide fractions could promote antitumor activity. Tuber polysaccharides from Tuber fermentation system exhibited relatively higher than that from Tuber fruiting bodies. These results confirm the potential of Tuber fermentation mycelia for use as an alternative resource for its fruiting bodies.

OBJECTIVE: To study the association between wheezing and Mycoplasma pneumoniae (MP) infection in infants and young children. METHODS: A total of 228 hospitalized infants and young children who were diagnosed with lower respiratory tract infection were enrolled and classified into initial wheezing group (n=65), recurrent wheezing group (n=83), and non-wheezing group (n=80). Fasting serum was collected on the day or the second day of admission. ELISA was used to measure MP-IgM, chemiluminescence was used to measure serum total immunoglobulin E (TIgE), and EUROLine was used to measure the common serum allergen specific immunoglobulin E (sIgE). The data on the manifestations of atopic constitution and the family history of allergic diseases were collected. RESULTS: The initial wheezing group and the recurrent wheezing group showed significantly higher positive MP infection rate and serum TIgE level than the non-wheezing group (P < 0.05). The recurrent wheezing group showed a significantly higher positive rate of sIgE than the initial wheezing group and the non-wheezing group (P < 0.05), and in these patients, the manifestations of atopic constitution and the family history of allergic diseases were closed associated with the pathogenesis of wheezing. CONCLUSIONS: MP infection is closely associated with wheezing in infants and young children. MP is one of the most common pathogens for wheezing in infants and young children, and the allergen sIgE, atopic constitution, and a family history of allergic diseases are important risk factors for recurrent wheezing.

Peroxisome proliferators activated receptors (PPARs) are closely related to human chronic disease, such as diabetes mellitus and the other metabolic diseases. In this study, a cell-based PPARs (PPAR α/β/γ) model was developed for the screening of PPARs agonists from Alismatis Rhizoma (AR). Firstly, 293T cells were transfected with the reconstructed plasmid pBind-PPAR (α, β, or γ)-LBD and reporter gene pGL4.35, and the known PPARs agonists were used as the positive control (fenofibrate for PPARα, L165041 for PPARβ, and rosiglitazone for PPARγ). The ability of activation for PPARs was evaluated by analyzing the expression value of luciferase. Afterward, the 14 pure triterpenoids isolate from AR were analyzed on the developed PPARα, PPARβ and PPARγ screening assay method. The results showed that the compounds 5, 6, 7, 8, 13 and 14 from AR have the ability of activation for PPARα. The compounds 5 and 7 from AR have the ability of activation for PPARβ. The compounds 6, 7, 8 and 12 from RA have the ability of activation for PPARγ.In this study, the compound 12 from AR were found to display significant activation on PPARγ for the first time. AR triterpenoids extracts had the ability of activation for PPARα, PPARβ and PPARγ. The results suggested that triterpenoids extracts from AR were PPARα, PPARβ and PPARγ agonists. The results will help to provide reference for clinical application of AR, and establish a model for PPARs on 293T cell, which can be used to screen and evaluate PPARs natural agonists.

Oxidative stress is an important pathogenesis of insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). Studies have shown that knockdown of PTEN-induced putative kinase 1 (PINK1) causes oxidative stress and mitophagy. In db/db mice, PINK1 protein level is down-regulated. However, little is known regarding the mechanism by which PINK1 modulates IR in response to reactive oxygen species (ROS) induced stress. In our study, PINK1 expression decreased during palmitate (PA) induced IR in HepG2 cells and the hepatic tissues of high fat diet (HFD) fed mice. Additionally, free fatty acids (FFAs) could increase ROS and suppress insulin signaling pathway, which was indicated by reduced phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3β (GSK-3β). In addition, insulin induced glucose uptake decreased and the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), two key gluconeogenic enzymes, was up-regulated after PA treatment. Intriguingly, PINK1 overexpression could lead to opposite results. Moreover, PA induced hepatic IR through C-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) pathways, which were rescued by PINK1 overexpression. In summary, our results demonstrate that PINK1 promoted hepatic IR via JNK and ERK pathway in PA treated HepG2 cells, implying a novel molecular target for the therapy of diabetes.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‑associated mortality worldwide. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are two common risk factors for HCC. The majority of patients with HCC present at an advanced stage and are refractory to therapy. It is important to identify a method for efficient diagnosis at early stage. In the present study gene expression profile data, generated from microarray data, were pretreated according to the annotation files. The genes were mapped to pathways of Ingenuity Pathways Analysis. Dysregulated pathways and dysregulated pathway pairs were identified and constructed into individual networks, and a main network was constructed from individual networks with several edges. Random Forest (RF) classification was introduced to calculate the area under the curve (AUC) value of this network. Subsequently, 50 runs of Monte Carlo cross‑validation were used to screen the optimal main network. The results indicated that a total of 4,929 genes were identified in the pathways and gene expression profile. By combining dysregulated pathways with Z

Objective The insulin-pancreatic acinar axis may play a major role in pancreatic function. Amylase is an exocrine enzyme that is produced by pancreatic acinar cells, and low serum amylase levels may be associated with endocrine diseases, such as metabolic syndrome and diabetes. We hypothesized that low serum amylase levels may be associated with impaired islet β cell function in type 2 diabetes. Therefore, we investigated the relationship between the serum amylase levels and islet β cell function in patients with early type 2 diabetes. Methods The cross-sectional study recruited 2327 patients with a mean of 1.71±1.62 years since their diagnosis of type 2 diabetes, and all participants were treated with lifestyle intervention alone. Serum amylase levels, the 75-g oral glucose tolerance test (OGTT) and metabolic risk factors were examined in all participants. The insulin sensitivity index (Matsuda index, ISIMatsuda) and insulin secretion index (ratio of total area-under-the-insulin-curve to glucose-curve, AUCins/glu) were derived from the OGTT. Integrated islet β cell function was assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2) (ISIMatsuda multiplied by AUCins/glu). Results Serum amylase levels in the normal range were significantly correlated with ISIMatsuda, AUCins/glu and ISSI-2 (r = 0.203, 0.246 and 0.413, respectively, p

Three well-known Australian beaches, Surfers Paradise Beach (Gold Coast), Narrowneck Beach (Gold Coast) and Bondi Beach (Sydney), were selected for analysis of beach user preferences for certain weather and ocean conditions. Regression methods were used to determine how the numbers of visitors to these beaches are affected by these conditions. Actual visitor numbers were counted at three times during the day over several months at each beach with the aid of web cameras. The corresponding weather and ocean conditions were obtained from the Australian Bureau of Meteorology and local government agencies. Weekly and seasonal factors were also considered. The conditions preferred by beach users, as found in this study, are: no precipitation, higher temperatures, light-to-moderate wind speed (less than 30 km/h) and low wave height (up to 1.25 m). This study, the first to provide an analysis of beach user preferences for both weather and ocean conditions, shows that ocean conditions play a significant role in explaining the demand for beach recreation in Australia. It is therefore necessary for tourism management authorities or local governments to provide accurate and timely weather and ocean information to local, domestic and international beach users.

Cardiac allograft vasculopathy is the leading cause of death after the first year of heart transplantation. The optimal treatment for unprotected left main coronary artery disease in orthotopic heart transplantation (OHT) patients is unknown. Two OHT patients with left main disease following heart transplantation underwent percutaneous coronary intervention (PCI). Technical success was achieved in the patients with drug-eluting stents inserted to cover the lesions in the left main coronary artery. After 16 months follow-up, one patient died of multiorgan failure, the other was alive and free from myocardial infarction or target vessel revascularization. We conclude that the unprotected PCI for the left main coronary artery stenosis in transplanted heart is feasible.

To investigate the irregular antibody production and its relationship with Rh factor genotypes and the loci of thalassemia gene mutations for the β-thalassemic children with long-term transfusion, so as provide experimental basis for clinical safe and effective transfusions for thalassemic children.The peripheral blood from 246 children with β-thalassemia was collected in our hospital; the extraction of genomic DNA and Rh factor (C/c, E/e) genotypes were assayed by PCR-SSP method, the irregular antibodies were screened and identified by serological method, the genotypes for thalassemia and gene mutations were analysed by PCR-RD method.The genotypes of Rh factors classified by PCR- SSP in the 246 cases of β-thalassemia children were as follws: Ce/Ce (143/246, 58.1%), CE/ce (59/246, 24%), cE/cE (14/24, 5.7%), Ce/ce (12/246, 4.9%); The positive rate of irregular antibody was 7.7% (19/246), including anti-E (7/19), anti-c (5/19), anti-C (2/19), anti-E and anti-c (2/19), anti-e (1/19), anti-D (2/19); Of the 19 cases with positive irregular antibody, the genotypings of Rh factor were: Ce/Ce (11/19), CE/ce (2/19), cE/cE (2/19), Ce/ce (2/19), cE/ce (2/19); the gene mutations location of thalassemia for 19 cases with positive irregular antibody: CD41-42M (13/19), CD71-72M (2/19), IVS-II-654M (3/19), -28M (1/19).The irregular antibody production for β-thalassemic children with long-term transfusion may have some relevance with Rh factor genotypes and thalassemia genetic mutations. This study possesses a certain significance for effective prevention of RBC alloimmune response of β-thalassemia children and improvement of efficacy and safety of clinical transfasion blood.

To explore the relationship between inflammation, oxidative stress and poor myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI).Risk factors and mechanisms of poor reperfusion in patients with STEMI after primary PCI remain unclear.A total of 143 patients who underwent primary PCI after STEMI were divided into good and poor perfusion groups according to sum-ST-segment resolution (sumSTR) and TIMI myocardial perfusion grade (TMP) results. Aortic sinus arterial blood was collected after primary PCI. The platelet-leukocyte aggregation (PLA), platelet-neutrophil aggregation (PNA), platelet-monocyte aggregation (PMA) and platelet-lymphocyte aggregation (PLyA) were measured by flow cytometry. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by chemical colorimetry.The leukocyte count, neutrophil ratio and high-sensitivity C-reactive protein were significantly higher in the poor perfusion group than the good perfusion group (p 0.05). Multiple linear regression analysis showed that neutrophil ratio was an independent risk factor of sumSTR in STEMI patients after primary PCI (p 0.01). The poor myocardial perfusion group had higher levels of PLA, PNA, PMA and MDA (p 0.05). There were no differences in PLyA and SOD levels between the good and poor myocardial perfusion groups (p 0.05).Inflammation and oxidative stress were related to poor myocardial perfusion in patients with STEMI after primary PCI.

The aim of the study was to evaluate the outcome of adenovirus-mediated p27KIP1 (Ad-p27) expression on wound healing after filtration surgery and to investigate the inhibition of cell proliferation induced by Ad-p27. We constructed the adenovirus recombinant vector Ad-p27 and administered it to a rabbit model of glaucoma filtration surgery by subconjunctival injection; phosphate-buffered saline (PBS) and mitomycin C (MMC) were used as controls. Intraocular pressure (IOP), bleb scores, and anterior chamber depths were observed during a 28-d period. Histological examinations, fluorescence observations and Western blot analyses were evaluated. Ad-p27 enhanced the surgical outcome and inhibited cell proliferation when compared with PBS. Bleb scores in the Ad-p27-treated eyes were higher than those in the PBS-treated eyes on d 7 (P

BACKGROUND Computer-aided diagnosis (CAD) of lung cancer is the subject of many current researches. Statistical methods and artificial neural networks have been applied to more quantitatively characterize solitary pulmonary nodules (SPNs). In this study, we developed a CAD scheme based on an artificial neural network to distinguish malignant from benign SPNs on thin-section computed tomography (CT) images, and investigated how the CAD scheme can help radiologists with different levels of experience make diagnostic decisions. METHODS Two hundred thin-section CT images of SPNs with proven diagnoses (135 small peripheral lung cancers and 65 benign nodules) were analyzed. Three clinical features and nine CT signs of each case were studied by radiologists, and the indices of qualitative diagnosis were quantified. One hundred and forty nodules were selected randomly to form training samples, on which the neural network model was built. The remaining 60 nodules, forming test samples, were presented to 9 radiologists with 3 - 20 years of clinical experience, accompanied by standard reference images. The radiologists were asked to determine whether a nodule was malignant or benign first without and then with CAD output. Diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis. RESULTS CAD outputs on test samples had higher agreement with pathological diagnoses (Kappa = 0.841, P < 0.001). Compared with diagnostic results without CAD output, the average area under the ROC curve with CAD output was 0.96 (P < 0.001) for junior radiologists, 0.94 (P = 0.014) for secondary radiologists and 0.96 (P = 0.221) for senior radiologists, respectively. The differences in diagnostic performance with CAD output among the three levels of radiologists were not statistically significant (P = 0.584, 0.920 and 0.707, respectively). CONCLUSIONS This CAD scheme based on an artificial neural network could improve diagnostic performance and assist radiologists in distinguishing malignant from benign SPNs on thin-section CT images.

// Chunming Jiang 1, * , Fang Shen 2, * , Jianmin Du 1 , Zhaoyang Hu 3 , Xiaoli Li 1 , Jin Su 4 , Xiaohua Wang 5 , Xianmei Huang 1 1 Department of Pediatrics, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang 310003, P.R. China 2 Department of Psychiatry, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310012, P.R. China 3 Translational Medicine Office of Hangzhou Cancer Institute, Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou First People’s Hospital, Hangzhou, Zhejiang 310003, P.R. China 4 Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China 5 Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China * Chunming Jiang and Fang Shen are co-first authors Correspondence to: Xianmei Huang, e-mail: hxianmei630715@163.com Keywords: glioblastoma, microRNA-564, TGF-β, proliferation Received: September 05, 2015 Accepted: January 23, 2016 Published: April 26, 2016 ABSTRACT Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-β1 (TGF-β1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-β. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-β-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-β1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.

The transcription factor, interferon regulatory factor 5 (IRF5), is important in the induction of type I interferon, proinflammatory cytokines and chemokines, and is involved in autoimmune diseases and tumourigenesis. However, the mechanisms underlying the transcriptional regulation of wild‑type IRF5 remain to be fully elucidated. The present study was primarily designed to clarify whether specificity protein 1 (Sp1) was involved in the regulation of IRF5. Initially, the IRF5 promoter region was cloned and its promoter activity was examined using Hela and HEK 293 cells. Deletion analyses revealed that the region spanning ‑179 to +62 was the minimal promoter of IRF5. Bioinformatics analyses showed that this region contained three putative Sp1 binding sites, and mutational analyses revealed that all the Sp1 sites contributed to transcriptional activity. Secondly, the overexpression of Sp1 was found to increase the activity of the IRF5 promoter and the mRNA level of IRF5, determined using reporter gene assays and polymerase chain reaction analysis, respectively. By contrast, treatment with mithramycin and Sp1 small interfering RNA significantly reduced the activity of the IRF5 promoter and the mRNA level of IRF5. Finally, the results of an electrophoretic mobility shift assay and a chromatin immunoprecipitation assay demonstrated that Sp1 bound to the promoter region of IRF5 in vitro and in vivo. These results suggested that the Sp1 transcription factor is the primary determinant for activating the basal transcription of the IRF5.

Background The goal of the current study was to evaluate the economic impact of propofol as compared with midazolam for sedating patients in the intensive care unit (ICU). Methods A randomized, unblinded, multicenter pharmacoeconomic trial captured health resource utilization and outcome measurements associated with sedation and treatment of patients in four ICUs across Canada. Statistical analysis was performed to investigate the difference in sedation quality, ICU length of stay, and other health resources used. The authors compared the costs (1997 Canadian dollars) associated with the two treatments. Two types of sensitivity analyses were performed. Results Although overall sedation duration was similar, propofol patients spent more time at adequately sedated status (60.2% vs. 44%; P = 0.01) and were extubated faster (median extubation time, 2.5 vs. 7.1 h; P = 0.001). The ICU length of stay and health resource utilization did not differ. The total cost per patient, including drug cost and ICU stay cost, did not differ between groups (median, $5,718 for propofol vs. $5,950 for midazolam; P = 0.94). The first sensitivity analysis suggested that the incremental cost (per patient) of propofol varies from an extra cost of $114 to a savings of $2,709. Based on a hypothetical model, the second sensitivity analysis showed a potential saving of $479 per patient as a result of improved discharge planning. Conclusion The analysis demonstrated that using propofol resulted in a reduction of time to extubation and higher sedative regimen costs. There was no difference in intensity of resource use or ICU length of stay and hence in costs. Issues regarding discharge delay among propofol-treated patients remain to be explored.

Aims: To evaluate the safety and efficacy of a new approach for transseptal catheterization in patients undergoing percutaneous balloon mitral valvuloplasty (PBMV). Methods: One hundred and two patients with rheumatic mitral stenosis were randomized into two groups. In the study group (RA approach), an imaginary horizontal line was drawn from the top end of the tricuspid valve under anteroposterior fluoroscopic view. The intersection of the horizontal line and the right edge of the corresponding thoracic vertebra was defined as the upper border of the Fossa ovalis. The atrial septum was punctured from a point 0.5 cm below the upper border of the Fossa ovalis. In the control group (LA approach), an imaginary horizontal line was drawn between the upper and middle third of the left atrium, and the intersection of this horizontal line and the right edge of the corresponding thoracic vertebra was used as an atrial septum puncture point. Results: Atrial septum puncture succeeded in all patients in the study group and in 72.6% of the patients in the control group (p < 0.01). The average fluoroscopy times for transseptal catheterization in the study and the control groups were 2.0 ± 0.5 and 3.0 ± 1.0 min, respectively (p < 0.01). Transseptal catheterization was subsequently achieved using the RA approach in the 14 patients from the control group in whom the LA approach failed. Conclusions: The RA approach is a safe and effective means for transseptal catheterization in patients undergoing PBMV.

To explore the value of multiple b-value diffusion-weighted imaging (DWI) for differentiation of benign and malignant pulmonary masses.Thirty-eight patients were examined by routine sequences and DWI pulse sequence. DWI was acquired through a single-shot echo-planar imaging combined with a respiratory-triggered mode and parallel acquisition. Nine b values ranging from 0 to 1500 s/mm(2) (0, 50, 100, 150, 200, 400, 600, 1000, 1500 s/mm(2)) were used. The intravoxel incoherent motion model was applied to estimate pure diffusion coefficient D, perfusion-related diffusion coefficient D(*), and perfusion fraction f. Mann-Whitney U test was used to compare all measured parameters between benign and malignant groups. The diagnostic performance of the related parameters was evaluated with receiver operating characteristics (ROC) analysis.Of these 38 patients, 30 were pathologically confirmed and 8 were diagnosed based on clinical data. There were 23 lung malignant masses and 15 benign lesions. A significant reduction of D was found in malignant group than in benign group (Z=3.308, P=0.001), while no significant differences in D(*)(Z=1.646, P=0.100) and f(Z=1.254, P=0.210) were observed between the two groups. The area under the ROC curve for D value (0.839) was largest. When the cutoff value was selected as 0.90×10(-3) mm(2)/s, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of diagnosing malignant masses were 95.7%, 80.0%, 90.9%, 91.7%, and 88.9%,respectively.The D value in multiple b-value DWI has certain significance in differentiating the benign and malignant pulmonary masses and has the best diagnostic efficiency.

Type 1 insulin-like growth factor receptor (IGF-1R) is a promising therapeutic target for cancer treatment. A single-chain variable fragment (scFv) against human IGF-1R forms inclusion body when expressed in periplasmic space of E. coli routinely. Here, we described that co-expression of appropriate disulfide bonds (Dsb) proteins known to catalyze the formation and isomerization of Dsb can markedly recover the soluble expression of target scFv in E. coli. A 50 % recovery in solubility of the scFv was observed upon co-expression of DsbC alone, and a maximum solubility (80 %) was obtained when DsbA and DsbC were co-expressed in combination. Furthermore, the soluble scFv present full antigen-binding activity with IGF-1R, suggesting its correct folding. This study also suggested that the selection of Dsb proteins should be tested case-by-case if the approach of co-expression of Dsb system is adopted to address the problem of insoluble expression of proteins carrying Dsb.

Background. Each province in Canada independently assesses drugs for their reimbursement eligibility. Publicly funded access to specific drugs is therefore dependent on province of residence. Objective. Evaluate the variability of access and its determinants for publicly available prescription drugs across Canada, and discuss the feasibility of implementing a national plan. Methods. For a sample of 58 drugs receiving Health Protection Branch approval in Canada between 01/01/1996 and 12/31/1997, all provinces were surveyed about their formulary inclusion/exclusion decision. Kappa values were estimated to measure concordance between provincial coverage decisions. Logistic analysis using Generalized Estimating Equations was used to assess the impact of key features of provincial plans on the decision. Results. Among the 58 drugs, 5 (9%) were included in all 10 and 14 (24%) by at least 8 provincial formularies. None were e-cluded by all the provinces. Concordance rates among provinces were low (overall κ-like statistic = 0.20 and range of pairwise κ = -0.11 to 0.64). Logistic regression showed that therapeutic category, price ratio to comparator, the integration of public with private coverage, and the e-istence of ability-to-pay criteria were significant determinants of the inclusion decision. Conclusions. Findings show that public access to the same prescription medications differs widely across provinces. If Canada were to adopt a “National” plan without disrupting current individual prescriptions, all currently funded drugs in each province would have to be “grandfathered” and included in the new National formulary. Such an all-inclusive list would also make such a plan unaffordable.

To estimate survival, the number of life-years gained and cost effectiveness of antiretroviral therapy (ART) regimens, denoted as ERA-I [zidovudine + (didanosine or zalcitabine)]; ERA-II [stavudine + (didanosine or zalcitabine) or lamivudine + (zidovudine or didanosine or zalcitabine or stavudine)]; and ERA-III [2 nucleoside reverse transcriptase inhibitors + (1 protease inhibitor or 1 non-nucleoside reverse transcriptase inhibitor)].Modelling of drug cost, cost of opportunistic diseases and survival of HIV positive men and women in the province of British Columbia who were first prescribed any ART between October 1992 and June 1996. A 'reference cohort' was modelled upon individuals in a longitudinal cohort of homosexual men followed since 1982. PERSPECTIVE AND SETTING: Third-party payer perspective in British Columbia, Canada.All HIV-positive men and women agedor =18 years with CD4+ countsor =350 cells/microL who were enrolled in the province-wide drug treatment programme.Annual costs, survival and cost-effectiveness ratios of successive ART regimens.Total costs [1997 Canadian dollars ($Can)] at 12 months under ERA-I, -II and -III were $Can4897, $Can6620 and $Can 11 914, respectively. Survival at 12 months under ERA-I, -II and -III was 89.6%, 91.0% and 97.6%, respectively. The annual incremental cost (estimated by the total incremental cost at 12 months) between ERA-II and ERA-I was $Can1723. The incremental cost-effectiveness ratios between ERA-III and ERA-I, and between ERA-III and ERA-II were $Can58 806 and $Can46 971 per life-year gained, respectively.We found the cost effectiveness of ERA-III ART regimens well within the range of currently funded therapies for the treatment of other chronic diseases.

The purpose of this study is to model the potential economic impact of viral load-driven triple drug combination (including a protease inhibitor) antiretroviral therapy on incremental drug and hospitalisation costs among individuals with HIV disease. Individuals included in the study were HIV-positive men and women from the province of British Columbia, Canada, who were aged 18 years or older and had given consent to access their medical records. The study employed pharmacoeconomic modelling of drug- and hospital-utilisation patterns among a population-based cohort with free access to antiretroviral therapy. Protease inhibitor use and associated costs based on actual use in a subsequent period was modelled upon men and women who were able to maintain stable CD4+ cell counts (slopeor = 0) for at least 6 months (baseline period) with an average follow-up period of 30 months (protease-like group). A control was modelled upon individuals with declining CD4+ cell counts (slope0) during similar baseline and follow-up periods. The primary outcome measure was average annual incremental cost of triple drug therapy net of hospitalisation and testing costs in 1996 Canadian dollars ($Can). The utilisation pattern of drugs and hospitals was modelled from actual use among a total of 1271 individuals who were eligible for this analysis. Programme participants who gave consent to access their medical records were more likely to be men (p0.001), older (p0.020), and on antiretroviral therapy (p0.001) than programme participants who did not give consent. No differences were observed between the protease-like and comparison groups with respect to age (p = 0.65) and CD4+ cell count (p = 0.30) at study entry. Over a period of 1 year, the protease-like group was shown to spend less time in hospital (2.7 vs 6.6 days; p0.001). This difference in hospitalisation remained in multivariate models, adjusting for prior AIDS-defining illnesses and gender. The average annual incremental cost of adding a protease inhibitor to a 2-drug antiretroviral regimen was estimated to be $Can2318 per person. The cost implications of hospital stay while using a protease inhibitor drug and 2 nucleosides translated into an average annual incremental cost (savings if negative) of between -$Can4798 and -$Can2227 per person. The overall average annual incremental cost impact per person associated with triple drug therapy with a protease inhibitor varied between -$Can2288 to $Can283. Negative incremental costs imply overall savings from adopting triple combination therapy. This modelling exercise demonstrated that the cost of triple drug combination antiretroviral therapy with a protease inhibitor among HIV-positive men and women was considerably less than the expected acquisition cost of the drug alone due to hospitalisation savings in the province of British Columbia.