Joint toxicity of cadmium (II) and microplastic leachates on wheat seed germination and seedling growth.

Cadmium (Cd) pollution ranks first in soils (7.0%) and microplastics usually have a significant adsorption capacity for it, which could pose potential threats to agricultural production and human health. However, the joint toxicity of Cd and microplastics on crop growth remains largely unknown. In this study, the toxic effects of Cd2+ and two kinds of microplastic leachates, polyvinyl chloride (PVC) and low-density polyethylene (LDPE), on wheat seed germination and seedlings' growth were explored under single and combined conditions. The results showed that Cd2+ solution and two kinds of microplastic leachates stimulated the wheat seed germination process but inhibited the germination rate by 0-8.6%. The combined treatments promoted wheat seed germination but inhibited the seedlings' growth to different degrees. Specifically, the combination of 2.0 mg L-1 Cd2+ and 1.0 mgC L-1 PVC promoted both seed germination and seedlings' growth, but they synergistically increased the antioxidant enzyme activity of seedlings. The toxicity of the PVC leachate to wheat seedlings was stronger than LDPE leachate. The addition of Cd2+ could alleviate the toxicity of PVC leachate on seedlings, and reduce the toxicity of LDPE leachate on seedlings under the same concentration class combinations but aggravated stress under different concentration classes, consistent with the effect on seedlings' growth. Overall, Cd2+, PVC, and LDPE leachates have toxic effects on wheat growth, whether treated under single or combined treatments. This study has important implications for the joint toxicity of Cd2+ solution and microplastic leachates in agriculture.

Protocol of the CONSORT and SPIRIT Extension for multicenter clinical trials.

Background: Multicenter clinical trials play an indispensable role for assessing the efficacy of a new intervention or treatment, particularly in Phase II or III studies. Previous studies have shown that these studies often suffer from inadequate reporting of key details related to their design, implementation, and analysis, both in the protocol and final reports. This limitation reduces the practical and scientific value of the findings. Furthermore, the lack of guidance on how to report multicenter features can contribute to poor reporting. Therefore, this study aims to develop guidelines to improve the reporting of multicenter trials, including two Extensions of the CONSORT 2010 and the SPIRIT 2013. Methods/design: The standard methodology for developing health research reporting guidelines involves the following steps: (i) Identifying the need for development and launching the research project; (ii) Preparing the registration and reviewing the literatures; (iii) Proposing the initial Checklists and conducting the Delphi exercise; (iv) Arranging the consensus meeting and formulating the Checklists; (v) Conducting the pilot test and drafting explanatory documents (E&E); (vi) Seeking comments from advisory group and finalizing the guidelines; and (vii) Developing the publication and dissemination strategies. Conclusion: By using the CONSORT and SPIRIT checklists as starting points, the development of extensions specific to multicenter trials can help researchers design and report high-quality clinical research. This, in turn, can facilitate the application of study findings in the current evidence-based healthcare system.

Construction of SLC16A1/3 Targeted Gallic Acid-Iron-Embelin Nanoparticles for Regulating Glycolysis and Redox Pathways in Cervical Cancer.

SLC16A1 and SLC16A3 (SLC16A1/3) are highly expressed in cervical cancers and associated with the malignant biological behavior of cancer. SLC16A1/3 is the critical hub for regulating the internal and external environment, glycolysis, and redox homeostasis in cervical cancer cells. Inhibiting SLC16A1/3 provides a new thought to eliminate cervical cancer effectively. There are few reports on effective treatment strategies to eliminate cervical cancer by simultaneously targeting SLC16A1/3. GEO database analysis and quantitative reverse transcription polymerase chain reaction experiment were used to confirm the high expression of SLC16A1/3. The potential inhibitor of SLC16A1/3 was screened from Siwu Decoction by using network pharmacology and molecular docking technology. The mRNA levels and protein levels of SLC16A1/3 in SiHa and HeLa cells treated by Embelin (EMB) were clarified, respectively. Furthermore, the Gallic acid-iron (GA-Fe) drug delivery system was used to improve its anti-cancer performance. Compared with normal cervical cells, SLC16A1/3 mRNA was over-expressed in SiHa and HeLa cells. Through the analysis of Siwu Decoction, a simultaneously targeted SLC16A1/3 inhibitor EMB was discovered. It was found for the first time that EMB promoted lactic acid accumulation and further induced redox dyshomeostasis and glycolysis disorder by simultaneously inhibiting SLC16A1/3. The gallic acid-iron-Embelin (GA-Fe@EMB) drug delivery system delivered EMB, which had a synergistic anti-cervical cancer effect. Under the irradiation of a near-infrared laser, the GA-Fe@EMB could elevate the temperature of the tumor area effectively. Subsequently, EMB was released and mediated the lactic acid accumulation and the GA-Fe nanoparticle synergistic Fenton reaction to promote ROS accumulation, thereby increasing the lethality of the nanoparticles on cervical cancer cells. GA-Fe@EMB can target cervical cancer marker SLC16A1/3 to regulate glycolysis and redox pathways, synergistically with photothermal therapy, which provides a new avenue for the synergistic treatment of malignant cervical cancer.

APOE as potential biomarkers of moyamoya disease.

Objective: The mechanisms underpinning Moyamoya disease (MMD) remain unclear, and effective biomarkers remain unknown. The purpose of this study was to identify novel serum biomarkers of MMD. Methods: Serum samples were collected from 23 patients with MMD and 30 healthy controls (HCs). Serum proteins were identified using tandem tandem-mass-tag (TMT) labeling combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins (DEPs) in the serum samples were identified using the SwissProt database. The DEPs were assessed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, Gene Ontology (GO), and protein-protein interaction (PPI) networks, and hub genes were identified and visualized using Cytoscape software. Microarray datasets GSE157628, GSE189993, and GSE100488 from the Gene Expression Omnibus (GEO) database were collected. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) were identified, and miRNA targets of DEGs were predicted using the miRWalk3.0 database. Serum apolipoprotein E (APOE) levels were compared in 33 MMD patients and 28 Moyamoya syndrome (MMS) patients to investigate the potential of APOE to be as an MMD biomarker. Results: We identified 85 DEPs, of which 34 were up- and 51 down-regulated. Bioinformatics analysis showed that some DEPs were significantly enriched in cholesterol metabolism. A total of 1105 DEGs were identified in the GSE157628 dataset (842 up- and 263 down-regulated), whereas 1290 were identified in the GSE189993 dataset (200 up- and 1,090 down-regulated). The APOE only overlaps with the upregulated gene expression in Proteomic Profiling and in GEO databases. Functional enrichment analysis demonstrated that APOE was associated with cholesterol metabolism. Moreover, 149 miRNAs of APOE were predicted in the miRWalk3.0 database, and hsa-miR-718 was the only DE-miRNA overlap identified in MMD samples. Serum APOE levels were significantly higher in patients with MMD than in those without. The performance of APOE as an individual biomarker to diagnose MMD was remarkable. Conclusions: We present the first description of the protein profile of patients with MMD. APOE was identified as a potential biomarker for MMD. Cholesterol metabolism was found to potentially be related to MMD, which may provide helpful diagnostic and therapeutic insights for MMD.

Response of cross-correlations between high PM2.5 and O3 with increasing time scales to the COVID-19: different trends in BTH and PRD.

The air pollution in China currently is characterized by high fine particulate matter (PM2.5) and ozone (O3) concentrations. Compared with single high pollution events, such double high pollution (DHP) events (both PM2.5 and O3 are above the National Ambient Air Quality Standards (NAAQS)) pose a greater threat to public health and environment. In 2020, the outbreak of COVID-19 provided a special time window to further understand the cross-correlation between PM2.5 and O3. Based on this background, a novel detrended cross-correlation analysis (DCCA) based on maximum time series of variable time scales (VM-DCCA) method is established in this paper to compare the cross-correlation between high PM2.5 and O3 in Beijing-Tianjin-Heibei (BTH) and Pearl River Delta (PRD). At first, the results show that PM2.5 decreased while O3 increased in most cities due to the effect of COVID-19, and the increase in O3 is more significant in PRD than in BTH. Secondly, through DCCA, the results show that the PM2.5-O3 DCCA exponents α decrease by an average of 4.40% and 2.35% in BTH and PRD respectively during COVID-19 period compared with non-COVID-19 period. Further, through VM-DCCA, the results show that the PM2.5-O3 VM-DCCA exponents [Formula: see text] in PRD weaken rapidly with the increase of time scales, with decline range of about 23.53% and 22.90% during the non-COVID-19 period and COVID-19 period respectively at 28-h time scale. BTH is completely different. Without significant tendency, its [Formula: see text] is always higher than that in PRD at different time scales. Finally, we explain the above results with the self-organized criticality (SOC) theory. The impact of meteorological conditions and atmospheric oxidation capacity (AOC) variation during the COVID-19 period on SOC state are further discussed. The results show that the characteristics of cross-correlation between high PM2.5 and O3 are the manifestation of the SOC theory of atmospheric system. Relevant conclusions are important for the establishment of regionally targeted PM2.5-O3 DHP coordinated control strategies.

Influencing factors of depressive symptoms among undergraduates: A systematic review and meta-analysis.

OBJECTIVE: This systematic review aims to examine the influencing factors of undergraduates' depressive symptoms by summarizing the categories and intensity of the factors, to lay a foundation for subsequent research. METHODS: Two authors independently searched in Medline (Ovid), Embase (Ovid), Scopu, PsycINFO, PsycARTICLES, the Chinese Scientific Journal Database (VIP Database), China National Knowledge database (CNKI), and the WanFang database for cohort studies related to the influencing factors affecting depressive symptoms among undergraduates published prior to September 12, 2022. Adjusted Newcastle-Ottawa scale (NOS) was used to assess the risk of bias. Meta-analyses of regression coefficient estimates were performed to calculate pooled estimates with R 4.0.3 software. RESULTS: A total of 73 cohort studies were included, involving 46362 participants from 11 countries. Factors affecting depressive symptoms were classified into relational, psychological, predictors of response to trauma, occupational, sociodemographic and lifestyle factors. In Meta-analysis, 4 of 7 influencing factors were revealed to be statistically significant: negative coping (B = 0.98, 95%CI: 0.22-1.74), rumination (B = 0.06, 95%CI: 0.01-0.11), stress (OR = 0.22, 95%CI: 0.16-0.28) and childhood abuse (B = 0.42, 95%CI:0.13-0.71). No significant association was found in positive coping, gender and ethnicity. LIMITATIONS: The current studies have the problems of inconsistent use of scales and large heterogeneity of research design, making it difficult to summarize, which is expected to be further improved in future research. CONCLUSION: This review evidences the importance of several influencing factors of depressive symptoms among undergraduates. We advocate for more high-quality studies with more coherent and appropriate study designs and outcome measurement approaches in this field. TRIAL REGISTRATION: Systematic review registration: PROSPERO registration CRD42021267841.

The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel.

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. A single drug or physical barrier treatment does not achieve the ideal anti-adhesion effect. We developed a thermosensitive hydrogel (PPH hydrogel) consisting of poloxamer 407 (P407), poloxamer (P188), and hydroxypropyl methylcellulose (HPMC) co-blended. An injectable thermosensitive TA/MMC-PPH hydrogel was obtained by loading tannic acid (TA) with an anti-inflammatory effect and mitomycin C (MMC), which inhibits fibroblast migration or proliferation. The optimal prescriptions of PPH hydrogels with a suitable gelling time (63 s) at 37 °C was 20% (w/v) P407, 18% (w/v) P188, and 0.5% (w/v) HPMC. The scanning electron microscopy (SEM) revealed that the PPH hydrogel had a three-dimensional mesh structure, which was favorable for drug encapsulation. The PPH hydrogel had a suitable gelation temperature of 33 °C, a high gel strength, and complicated viscosity at 37 °C, according to the rheological analysis. In vitro release studies have shown that the PPH hydrogel could delay the release of TA and MMC and conform to the first-order release rate. Anti-adhesion tests performed on rats in vivo revealed that TA/MMC-PPH hydrogel significantly reduced the risk of postoperative adhesion. In conclusion, the TA/MMC-PPH hydrogel prepared in this study showed an excellent performance in both controlled drug release and anti-adhesive effects. It can be used as a protocol to prevent or reduce postoperative abdominal adhesion.

Extracellular Vesicles Derived from Bone Mesenchymal Stem Cells Carrying circ_0000075 Relieves Cerebral Ischemic Injury by Competitively Inhibiting miR-218-5p and Up-regulating E3 Ubiquitin Ligase SMURF2.

Extracellular vesicle (EV)-encapsulated circRNAs have the potential role in affecting brain disorders. However, the role of circ_0000075 in cerebral ischemic injury remains unclear. Here, we tried to investigate the mechanism of bone marrow mesenchymal stem cell (BMSC)-derived EVs carrying circ_0000075 in the control of cerebral ischemic injury. Initially, a mouse model with cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO), followed by the determination of circ_0000075 expression. Then, neurons were isolated and subjected to oxygen-glucose deprivation/reperfusion. BMSCs were isolated for extraction of EVs. The correlation among circ_0000075, microRNA (miR)-218-5p, and Smad ubiquitination regulatory factor 2 (SMURF2) was detected with their roles in cerebral ischemic injury analyzed in vivo and in vitro. circ_0000075 was down-regulated in MCAO mice and engineered RVG-EVs were internalized by neurons to up-regulate circ_0000075 expression. Treatment of RVG-circ_0000075-EVs reduced brain tissue damage, increased neuronal count, and significantly curtailed apoptosis rate, suppressing cerebral ischemic injury in vitro and in vivo. miR-218-5p was targeted by circ_0000075 in neurons, which promoted SMURF2 expression. A negative correlation between SMURF2 and transcriptional regulator Yin Yang 1 (YY1) was identified. In vitro experiments further proved that circ_ 00,000 75 could down-regulate the expression of YY1 through SMURF2, and finally relieving cerebral ischemic injury. Collectively, engineered EVs delivered circ_0000075 into brain tissues and increased circ_0000075 expression, which down-regulated miR-218-5p and up-regulated SMURF2, thus alleviating cerebral ischemic injury.

Fractal analysis of impact of PM2.5 on surface O3 sensitivity regime based on field observations.

Properties of PM2.5 that can change aerosol chemistry and photolysis rates have great impacts on O3 sensitivity regime, further affecting the production rate of surface O3. However, responses of O3 sensitivity regime to changes in PM2.5 levels are difficult to be accurately determined, due to the complexity and nonlinearity of atmospheric chemistry. Here, based on long-term time series (2016-2020) of air quality variables in north and south Taiwan, fractal analysis along with Pearson correlation analysis are used to directly reveal the impacts of PM2.5 on O3 sensitivity regime in real atmosphere, by capturing the nonlinear dynamic relations among air pollutants. Great regional and seasonal difference in impacts of PM2.5 on O3 sensitivity regime may be ascribed to meteorological factors, PM2.5 components and levels of SO2, NO, NO2, etc. For north Taiwan, increased PM2.5 level can enhance the sensitivity of O3 formation to VOC in spring and summer, whereas the opposite effect can be observed in winter. But for south Taiwan, the influence of PM2.5 on O3 sensitivity regime is not statistically significant, excluding spring. Furthermore, feasibility and availability of fractal analysis is tested by simulations with Empirical Kinetics Modeling Approach (EKMA). The results demonstrate the capability of fractal analysis to identify the impacts of PM2.5 on O3 sensitivity regime in real atmosphere, which can provide suggestions for PM2.5-O3 coordinated control strategies in regions suffering combined air pollution.

Promoting the quality and transparency of health research in China.

BACKGROUND AND OBJECTIVES: To review the efforts and progress in promoting quality and transparency of health research in China and to discuss how to improve. METHODS: We focused on three different types of health research: clinical trials, systematic reviews, and clinical practice guidelines, and summarized China's progress from their registration, implementation, and reporting stages. RESULTS: In the last 3 decades, China's major works include the following: 1) For registration, the trials and CPGs registries have been set up, and released policies to mandate registration and submission of protocols for trials. 2) For implementation, multiple clinical research and EBM centers have been established. The ResMan platform for data management has been created and required researchers to share results data. 3) For reporting, the Chinese EQUATOR Center has been set up. Translations and extensions of the CONSORT, PRISMA, and RIGHT have been published. 4) For traditional Chinese medicine (TCM), specific guidelines for the registration and reporting of TCM research have been developed. CONCLUSION: China has made progress in promoting research quality and transparency, especially in research registration and reporting. Nevertheless, more can be done in data management and sharing for research implementation, and good publication practices in TCM.

The Grading of Recommendations, assessment, development, and evaluation approach was rarely followed and inconsistently applied in pressure injury prevention guidelines development: A cross-sectional survey.

INTRODUCTION: The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was developed to assess the certainty (or quality) of evidence and strength of recommendations in guidelines and endorsed internationally as a standard. Some guidelines had been developed to promote pressure injury prevention. AIMS: We explored whether and to what extent the development of pressure injury prevention guidelines had followed or been informed by the GRADE approach. If this approach was not used, we examined which other methods were used instead. METHODS: A cross-sectional study of pressure injury prevention guidelines was conducted. PubMed, Embase, CINAHL, and Chinese databases as well as guideline repositories and websites of professional bodies were searched for guidelines from 1990 to 2020. The grading systems of the certainty (or quality) of evidence and strength of recommendations of included guidelines were extracted. For the GRADE approach guidelines, compliance was assessed with the GRADE application criteria. RESULTS: Twenty guidelines were identified. Among them, four guidelines (20%) indicated the use of the GRADE approach. The compliance rate ranged from 33.3%-94.4%. Other approaches, such as the Scottish Intercollegiate Guidelines Network (SIGN) approach, were also used. CONCLUSION: The GRADE approach is rarely followed and inconsistently applied in pressure injury prevention guidelines. Other systems, such as the SIGN approach, are being used despite being outdated or inconsistent. Strategies for further uptake and appropriate application of the GRADE approach among guideline developers are needed in the future.

Relation between lymphocyte to monocyte ratio and survival in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

Background: The lymphocyte-to-monocyte ratio (LMR) has been proposed as a novel prognostic factor in malignancies and cardiovascular diseases. Our study aimed to ascertain whether LMR is a useful biomarker in discriminating the hypertrophic cardiomyopathy (HCM) patients at higher risk of all-cause mortality. Methods: This retrospective study consisted of 354 adult HCM patients. Cox's proportional hazards regression models were used to analyze the association between LMR and all-cause mortality. Smooth curve fitting was conducted to explore the linear relationship between LMR and all-cause mortality. Results: During the follow-up, 44 patients reached the study endpoint. The all-cause mortality rate was 7.3 per 100 person-years in the first tertile and decreased across the three tertiles of LMR. With the first tertile as reference, adjusted hazard ratios (HR) for all-cause mortality were 0.43 for the second tertile (95% CI [0.20-0.91], p = 0.027) and 0.39 for the third tertile (95% CI [0.17-0.90], p = 0.028), respectively. Smooth curve fitting exhibited a nonlinear relationship between LMR values and all-cause mortality. For LMR < 6.5, per SD increase resulted in a significantly decreased risk of all-cause mortality by 62% (HR: 0.38, 95% CI [0.21-0.68]). For LMR ≥ 6.5, the all-cause mortality risk did not progressively increase. Stratified and subgroup analyses revealed similar results to the main analyses,andE-value analysis suggested robustness to unmeasured confounding. Conclusions: The study demonstrated that LMR was an independent predictor of all-cause mortality in HCM patients, and LMR may be useful for identifying HCM patients at high mortality risk.

The mediating role of coping styles in the relationship between perceived social support and antenatal depression among pregnant women: a cross-sectional study.

BACKGROUND: Antenatal depression (AD) is common in pregnant women and is associated with adverse outcomes for the mother, fetus, infant and child. The influencing factors of AD among pregnant women have been studied; however, the mechanisms of these factors remain unclear. This study was designed to examine the direct and serial mediating roles of coping styles in the relationship between perceived social support and AD among pregnant women. METHODS: A cross-sectional study was conducted among 1486 pregnant women who registered to give birth at a tertiary hospital. A self-developed questionnaire was administered to obtain sociodemographic and obstetric data. The Perceived Social Support Scale (PSSS), Simplified Coping Style Questionnaire (SCSQ), and Edinburgh Postnatal Depression Scale (EPDS) were administered to measure the perceived social support, coping styles, and depressive symptoms of pregnant women, respectively. Multiple linear stepwise regression analysis was used, and then, the specific relationships among influencing factors were determined through structural equation modelling (SEM). RESULTS: The prevalence of AD was 24.02%. The average scores of intrafamily support, extrafamily support, positive coping styles, negative coping styles and EPDS reported by pregnant women were 24.16 ± 3.09, 44.52 ± 6.16, 27.34 ± 4.89, 9.79 ± 3.82, and 7.44 ± 3.56, respectively. Multiple regression analysis showed that pregnant women with a higher level of intrafamily support exhibited a positive coping style and a decreased risk of AD. Compared with extrafamily support, the direct effect (-0.16 vs. -0.10, P < 0.05) and indirect effect of intrafamily support through coping styles (-0.028 vs. -0.027, P < 0.05) on AD were stronger. Two indirect pathways explained 17.46% of the variance in the EPDS scores. CONCLUSION: Higher social support decreased the likelihood of AD, not only directly but also through the mediating roles of coping styles. Social support should be strengthened, and positive coping styles should be advocated in every stage of pregnancy. Specifically, intrafamily support should be given more attention for pregnant Chinese women.

Anticancer nanomedicines harnessing tumor microenvironmental components.

INTRODUCTION: Small-molecular drugs are extensively used in cancer therapy, while they have issues of nonspecific distribution and consequent side effects. Nanomedicines that incorporate chemotherapeutic drugs have been developed to enhance the therapeutic efficacy of these drugs and reduce their side effects. One of the promising strategies is to prepare nanomedicines by harnessing the unique tumor microenvironment (TME). AREAS COVERED: The TME contains numerous cell types that specifically express specific antibodies on the surface. The physicochemical environment is characterized with a low pH, hypoxia, and a high redox potential resulting from tumor-specific metabolism. Therefore, intelligent nanomedicines designed based on the characteristics of the tumor microenvironment can be divided into two groups: the first group which is rapidly responsive to extracellular chemical/biological factors in the TME and the second one which actively and/or specifically targets cellular components in the TME. EXPERT OPINION: In this paper, we review recent progress of nanomedicines by harnessing the TME and illustrate the principles and advantages of different strategies for designing nanomedicines, which are of great significance for exploring novel nanomedicines or translating current nanomedicines into clinical practice. We will discuss the challenges and prospects of preparing nanomedicines to utilize or alter the TME for achieving effective, safe anticancer treatment.

Induction of cancer cell stemness in glioma through glycolysis and the long noncoding RNA HULC-activated FOXM1/AGR2/HIF-1α axis.

Gliomas are the most common primary intracranial tumor, accounting for more than 70% of brain malignancies. Studies indicate that highly upregulated in liver cancer (HULC), a long noncoding RNA (lncRNA), functions as an oncogene in gliomas. However, the underlying mechanism of HULC in gliomas remains under-studied and was subsequently investigated in the current study. Brain tissues were clinically collected from 50 patients with glioblastoma (GBM) and 35 patients with acute craniocerebral injury, followed by immunohistochemical detection of the expression patterns of Forkhead box M1 (FOXM1), anterior gradient 2 (AGR2), and hypoxia-inducible factor-1α (HIF-1α). After flow cytometry-based sorting of the CD133+ glioma stem cells (GSCs) from the U251 cell line, the obtained cells were subjected to lentivirus infection. Afterwards, the proliferation, stemness, and apoptosis of GSCs were evaluated using sphere formation, immunofluorescence, and flow cytometry assays, respectively. In addition, the interactions among HULC, FOXM1, AGR2, and HIF-1α were identified using RNA immunoprecipitation (RIP), RNA pull-down, Chromatin immunoprecipitation (ChIP), IP, and dual luciferase reporter assays. Last, the specific effects were validated in vivo. HULC was upregulated in GBM tissues and GSCs, which may promote the progression of glioma. On the other hand, silencing of HULC reduced the stemness, inhibited the proliferation, and promoted the apoptosis and differentiation of GSCs. In addition, HULC further stabilized FOXM1 expression in GSCs through ubiquitination, while FOXM1 activated AGR2 transcription to promote HIF-1α expression. Moreover, HULC promoted the glycolysis and stemness of GSCs through its regulation of the FOXM1/AGR2/HIF-1α axis, consequently exacerbating the occurrence and development of glioma. The findings obtained in our study indicate that HULC stabilizes the FOXM1 protein by ubiquitination to upregulate the expression of AGR2 and HIF-1α, which further promote the glycolysis of and maintain the stemness of GSCs, to enhance the tumorigenicity of GSCs, highlighting a novel therapeutic target for glioma.

Medication therapy of high-dose methotrexate: An evidence-based practice guideline of the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society.

AIMS: A lot of medication risks related to high-dose methotrexate (HDMTX) therapy still remain to be identified and standardized. This study aims to establish an evidence-based practice guideline for individualized medication of HDMTX. METHODS: The practice guideline was launched by the Division of Therapeutic Drug Monitoring, Chinese Pharmacological Society. The guideline was developed following the WHO handbook for guideline development and the methodology of evidence-based medicine (EBM). The guideline was initially registered in the International Practice Guidelines Registry Platform (IPGRP-2017CN021). Systematic reviews were conducted to synthesize available evidence. A multicentre cross-sectional study was conducted using questionnaires to evaluate patients' perception and willingness concerning individualized medication of HDMTX. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the quality of evidence and to grade the strength of recommendations. RESULTS: Multidisciplinary working groups were included in this guideline, including clinicians, pharmacists, methodologists, pharmacologists and pharmacoeconomic specialists. A total of 124 patients were involved to integrate patient values and preferences. Finally, the guideline presents 28 recommendations, regarding evaluation prior to administration (renal function, liver function, pleural effusion, comedications, genetic testing), pre-treatment and routine dosing regimen, therapeutic drug monitoring (necessity, method, timing, target concentration), leucovorin rescue (initial timing, dosage regimen and optimization), and management of toxicities. Of these, 12 are strong recommendations. CONCLUSIONS: We developed an evidence-based practice guideline with respect to HDMTX medication using a rigorous and multidisciplinary approach. This guideline provides comprehensive and practical recommendations involving the whole process of HDMTX administration to health care providers.

The methodological quality of surgical randomized controlled trials: A cross-sectional systemic review.

Systematic reviews of RCTs have been developed to address end-users' needs and are regarded as the highest level of evidence. Flaws in the design, conduct and analyses of a systematic review can lead to erroneous conclusions and increase the research waste. We undertook a cross-sectional survey to identify the critical areas of weakness in systematic reviews for surgical interventions by AMSTAR 2. We searched PubMed, EMbase and Cochrane Library to summarize systematic reviews of surgical RCTs published in 2017. The information regarding general characteristics and methodological characteristics were gathered. We conducted descriptive analyses of study characteristics of included systematic reviews and explored the difference among varied methodological quality. Totally 141 systematic reviews were identified. We found only four reviews (2.8%) were high quality, 3 (2.1%) were moderate quality, 8 (5.7%) were low quality, and the remaining 126 (89.4%) were of critical low quality. The critical weaknesses were lack of pre-registration or published protocols (29.1%), comprehensive literature search (17.7%), lists of excluded studies and reasons for exclusion (19.1%), description of detailed interventions (8.5%), extraction of funding source from included trials (10.6%), and consideration of the risk of bias of included trials when synthesized (16.3%) and interpret (20.6%) the results. Higher methodological quality was only positively associated with Cochrane systematic review. Although two-thirds of included systematic reviews in the field of surgery were published in journals ranking Q1, the methodological quality is suboptimal and needs to be substantially improved. More efforts of multi-disciplinary teams' collaboration, continual education and training, integrally connection between primary studies and systematic review and contributing surgical research to practice should be imperative.

The CRY2-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis.

Light and temperature are two key environmental factors that coordinately regulate plant growth and development. Although the mechanisms that integrate signaling mediated by cold and red light have been unraveled, the roles of the blue light photoreceptors cryptochromes in plant responses to cold remain unclear. In this study, we demonstrate that the CRYPTOCHROME2 (CRY2)-COP1-HY5-BBX7/8 module regulates blue light-dependent cold acclimation in Arabidopsis thaliana. We show that phosphorylated forms of CRY2 induced by blue light are stabilized by cold stress and that cold-stabilized CRY2 competes with the transcription factor HY5 to attenuate the HY5-COP1 interaction, thereby allowing HY5 to accumulate at cold temperatures. Furthermore, our data demonstrate that B-BOX DOMAIN PROTEIN7 (BBX7) and BBX8 function as direct HY5 targets that positively regulate freezing tolerance by modulating the expression of a set of cold-responsive genes, which mainly occurs independently of the C-repeat-binding factor pathway. Our study uncovers a mechanistic framework by which CRY2-mediated blue-light signaling enhances freezing tolerance, shedding light on the molecular mechanisms underlying the crosstalk between cold and light signaling pathways in plants.