Development, Evaluation, and impLemenTation for guideline adaptation: a quality improvement protocol for the DELTA study in global health practice.

BACKGROUND: Guideline adaptation is an emerging field to provide more appropriate recommendations for local clinical practice quality and to promote global health equity. However, its utilization status, adaptation procedures, and related materials remain to be studied. METHODS: This study developed a quality improvement protocol for a study as the Development, Evaluation, and impLemenTation for guideline Adaptation (DELTA) study. Current adapted clinical practice guidelines (CPGs) will be systematically searched. Their characteristics, utilization status, and adaptation procedures will be extracted, compared, and analyzed. Whether these adapted CPGs rigorously followed the instruments and steps of adaptation frameworks will also be appraised. In addition, the advantages and limitations of current adaptation methods and their suitable application situations will be analyzed. In addition, future perspectives as DELTA series and DELTA system, aiming for comprehensively evaluating current needs for guideline adaptation and developing a unified framework and related materials were proposed to improve the acceptability, applicability, and implementation of guideline adaptation in clinical practice. The DELTA series are divided into four phases: phase I in analyzing status, characteristics, and procedures and completeness of adapted CPGs; phase II in analyzing differences, heterogeneity, and implementation between adapted and original CPGs; and phase III in collecting, analyzing, and comparing all available adaptation materials. With these research bases, an international working group will be established in phase IV and will develop unified guideline adaptation materials after Delphi consensus, including adaptation frameworks, appraisal tools and checklists, registries, and databases. DISCUSSION: Guideline adaptation has been advanced as an efficient way to guide local clinical practice. However, it still faces several major challenges. The proposed DELTA study, series, and system will further contribute to this emerging topic. TRIAL REGISTRATION:  This study has been registered by the PROSPERO international database. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400170 .

Genome-wide identification of CXE and PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit.

Volatile esters are the main aromatic components that affect consumer sensory preferences. Aroma is a crucial characteristic of the 'Nanguo' pear (Pyrus ussriensis Maxim). Carboxylesterases (CXEs) are positively correlated with the catabolism of volatile esters in peaches; however, the mechanism of action of CXE family members in 'Nanguo' pear is poorly understood. In this study, 40 PuCXEs were identified in the 'Nanguo' pear and assigned into seven groups. In addition, we found that most PuCXEs were relatively conserved and contained cytoplasmic proteins. This hypothesis was supported by phylogenetic analysis, investigation of conserved domains and gene structures, and prediction of subcellular localization. Based on the content of volatile esters and expression levels of PuCXEs analysis, four PuCXEs, including PuCXE7, PuCXE15, PuCXE20, and PuCXE25, had a significant negative correlation with volatile ester accumulation. Particularly, the correlation of PuCXE15 far exceeded that of the other PuCXEs. The results of the transient expression assay showed that PuCXE15 promoted the degradation of ester in vivo. Subcellular localization experiment revealed that PuCXE15 is located in the plasma membrane and nucleus. These results show that PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit, and provides a foundation for enhancing aroma quality by artificial control in pear.

Stage-Specific Transcriptomes of the Mussel Mytilus coruscus Reveals the Developmental Program for the Planktonic to Benthic Transition.

Many marine invertebrate larvae undergo complex morphological and physiological changes during the planktonic-benthic transition (a.k.a. metamorphosis). In this study, transcriptome analysis of different developmental stages was used to uncover the molecular mechanisms underpinning larval settlement and metamorphosis of the mussel, Mytilus coruscus. Analysis of highly upregulated differentially expressed genes (DEGs) at the pediveliger stage revealed enrichment of immune-related genes. The results may indicate that larvae co-opt molecules of the immune system to sense and respond to external chemical cues and neuroendocrine signaling pathways forecast and trigger the response. The upregulation of adhesive protein genes linked to byssal thread secretion indicates the anchoring capacity required for larval settlement arises prior to metamorphosis. The results of gene expression support a role for the immune and neuroendocrine systems in mussel metamorphosis and provide the basis for future studies to disentangle gene networks and the biology of this important lifecycle transformation.

p53-driven replication stress in nucleoli of malignant epithelial ovarian cancer.

Malignancies including ovarian cancer (OvCa) are genetically unstable. Genomic integrity is maintained by tumor suppressor p53 and DNA damage response network, which crosstalk to each other via not well characterized mechanisms. In this work, we characterize features of damage-related signals in cultured epithelial OvCa cells and tumor biopsies. We found that endogenous burden of DNA damage in OvCa tissues were ubiquitously accumulated in high-grade malignancies than lower grade of cancer that cannot be obviously explained by disturbed function of in DNA damage response (DDR). In contrast, CHK1 phosphorylation (CHK1-pS345) marking the checkpoint activation in nucleolar compartments are prevalent in high-grade OvCa, coincident to the elevated DNA damage in nucleoplasm. Generation of CHK1-pS345 requires the presence of p53 protein in addition to the well-known activities of ATM/ATR kinases. Apparently, mutant forms of p53 possess higher activity in triggering CHK1 phosphorylation than wild type, implying a potential role of p53 in maintaining rDNA integrity. Loss of p53 function would cause replication stress in nucleoli. Altogether, our study reveals endogenous nucleoli stress in OvCa that is coupled to perturbed function of p53 in DNA repair.

Transplantation of umbilical cord blood-derived mesenchymal stem cells as therapy for adriamycin induced-cardiomyopathy.

Umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) have been reported to possess cardioprotective effects in diseases. However, its effects on cardiomyopathy remain unclear. This study aimed to the therapeutic effects of UCBMSC transplantation on adriamycin (ADR)-induced cardiomyopathy. UCBMSCs isolated from human UCB were identified by detecting surface markers (CD29, CD90, CD34, and CD45) using flow cytometry. The effect of UCBMSCs on left ventricular end-diastolic dimension (LVEDD), left ventricular systolic end-diastolic diameter (LVESD), left ventricular ejection fraction (LVEF), and left ventricular fraction shortening (LVFS) were determined by echocardiography. Histological changes were observed by HE and Masson staining. The serum levels of collagen-I (Col-I), brain natriuretic peptide (BNP), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), CK-MB, interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured by corresponding kits. The protein levels of IL-6, IL-10, and TNF-α were measured by Western blotting. The isolated UCBMSCs manifested the positive expression of CD29 and CD90, and the negative expression of CD34 and CD45. UCBMSC transplantation significantly reduced LVEDD and LVESD, and increased LVEF and LVFS in ADR-induced cardiomyopathy model rats. Cardiac injury and high collagen deposition in model rats were alleviated by UCBMSC treatment. Moreover, UCBMSCs decreased the serum levels of Col-I, BNP, AST, LDH, CK, CK-MB, IL-6, IL-10, and TNF-α in model rats. Overall, UCBMSCs exert the therapeutic effects on ADR-induced cardiomyopathy through recovering the myocadiac function and alleviating the inflammatory response.

miRNA-93-5p Promotes Gemcitabine Resistance in Pancreatic Cancer Cells by Targeting the PTEN-Mediated PI3K/Akt Signaling Pathway.

OBJECTIVE: To investigate the role and potential underlying mechanism of miR-93-5p in the carcinogenesis and gemcitabine resistance of pancreatic cancer (PC) cells. METHODS: We generated a gemcitabine-resistant PC cell line Bxpc-3/GemR following prolonged gemcitabine exposure to its parental gemcitabine-sensitive counterpart Bxpc-3/Par. Cell viability was monitored by MTS assay. Transfection was performed using Lipofectamine 3000 reagent. Cell apoptosis and rhodamine 123 fluorescence were detected by flow cytometry. Luciferase activities were measured using the luciferase reporter gene assay. Expression analysis was carried out by qRT-PCR and western blot. RESULTS: Significantly increased viability and enhanced expression of the multi-drug resistance-1 (MDR1) gene were observed in Bxpc-3/GemR cells, in which miR-93-5p is considerably upregulated, compared with Bxpc-3/Par cells. Downregulation of miR-93-5p inhibited cell viability, induced cell apoptosis, and decreased MDR1 expression in Bxpc-3/GemR cells, whereas upregulation essentially reversed these properties in Bxpc-3/Par cells. We further confirmed that PTEN was a direct target of miR-93-5p, and overexpression of miR-93-5p was accompanied by a significant increase in the phosphorylation of Akt expression in the Bxpc-3/Par cells. Moreover, inhibition of PI3K/Akt signaling diminished MDR1 expression. CONCLUSION: These observations suggest that miR-93-5p modulates tumorigenesis and gemcitabine resistance in PC cells via targeting the PTEN/PI3K/Akt signaling pathway.

[Influence of maternal and infant factors on CD34+ hematopoietic stem/progenitor cells in umbilical cord blood].

OBJECTIVE: To study the association of different maternal and infant factors with the number of total nucleated cells and CD34+ hematopoietic stem/progenitor cells in umbilical cord blood, and to provide a reference for reasonable selection of umbilical cord blood in the cord blood bank. METHODS: A prospective study was performed for the umbilical cord blood samples of 130 neonates who were born in Dalian Women and Children's Medical Center from June 2019 to January 2020, with a male/female ratio of 1:1. Related perinatal information was collected, including maternal age and blood type, presence or absence of gestational diabetes or gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/twin pregnancy, body weight and sex of neonates, Apgar score after birth, and the conditions of placenta, amniotic fluid, and umbilical cord. RESULTS: The neonates were grouped according to maternal blood type, gestational diabetes, gestational hypertension, pregnancy method, mode of delivery, singleton pregnancy/ twin pregnancy, sex of neonates, Apgar score after birth, placental morphology, meconium staining of amniotic fluid, and umbilical cord around the neck. The comparison between groups showed no significant differences in the numbers of total nucleated cells and CD34+ cells in umbilical cord blood (P > 0.05). Maternal age and neonatal body weight were not correlated with the number of total nucleated cells in umbilical cord blood (P > 0.05), and neonatal body weight was not correlated with the number of CD34+ cells (P > 0.05), while maternal age was positively correlated with the number of CD34+ cells (P < 0.05). CONCLUSIONS: The number of CD34+ cells in umbilical cord blood increases with the increase in maternal age, and therefore, umbilical cord blood in the cord blood bank may be selected based on maternal age.

Psychoactive substance abuse and associated factors among middle school students in Liaoning / 中国学校卫生

Objective@#To investigate psychoactive substance abuse and associated factors among middle school students in Liaoning, and to provide policy suggestions and reference opinions for relevant departments.@*Methods@#A questionnaire survey was conducted among 12 598 middle school students in 10 cities of Liaoning by multi stage stratified cluster sampling. Multivariate Logistic regression model was used to analyze associated factors of psychoactive substance abuse.@*Results@#About 0.94% ( n =118) of all participants reported substance abuse behavior, the highest abuse rate was in the third grade students in vocational middle school, the most common psychoactive substance was “laughing balloon”, accounting for 0.57%. Multivariate Logistic regression analysis revealed that girls, moderate academic burden were generally negatively associated with more psychoactive substance use( OR = 0.57 , 0.58, P <0.05). Academic performance class was ranked in the last ten, monthly pocket money more than 500 yuan and sleep with medication were generally positively associated with more psychoactive substance use ( OR =1.93, 2.52, 4.29, P < 0.05 ).@*Conclusion@#The problem of psychoactive substance abuse among middle school students can not be ignored. Effective prevention and control of psychoactive substance abuse can be achieved through publicity, education, awareness raising, early intervention, counseling and treatment, and through coordination of adolescents, families, schools, government and the society.

Cell type-specific genotoxicity in estrogen-exposed ovarian and fallopian epithelium.

BACKGROUND: Loss of the genomic stability jeopardize genome stability and promote malignancies. A fraction of ovarian cancer (OvCa) arises from pathological mutations of DNA repair genes that result in highly mutagenic genomes. However, it remains elusive why the ovarian epithelial cells are particularly susceptible to the malfunction of genome surveillance system. METHODS: To explore the genotoxic responses in the unique context of microenvironment for ovarian epithelium that is periodically exposed to high-level steroid hormones, we examined estrogen-induced DNA damage by immunofluorescence in OvCa cell lines, animal and human samples. RESULTS: We found that OvCa cells are burdened with high levels of endogenous DNA damage that is not correlated with genomic replication. The elevation of damage burden is attributable to the excessive concentration of bioactive estrogen instead of its chemomimetic derivative (tamoxifen). Induction of DNA lesions by estrogen is dependent on the expression of hormone receptors, and occurs in G1 and non-G1 phases of cell cycle. Moreover, depletion of homologous recombination (HR) genes (BRCA1 and BRCA2) exacerbated the genotoxicity of estrogen, highlighting the role of HR to counteract hormone-induced genome instability. Finally, the estrogen-induced DNA damage was reproduced in the epithelial compartments of both ovarian and fallopian tubes. CONCLUSIONS: Taken together, our study disclose that estrogen-induced genotoxicity and HR deficiency perturb the genome stability of ovarian and fallopian epithelial cells, representing microenvironmental and genetic risk factors, respectively.

The Effect of Activation Method of Rubber on the Performance of Modified Asphalt Binder.

Poor storage stability is a key problem restricting the rapid development and wide application of rubber-modified asphalt binder, and activation of rubber has shown good prospects to solve this problem. In this study, two activation methods, coating by polyamide 6 and grafting by acrylamide, were introduced to treat crumb rubber. Then the activated rubber was added to base asphalt binder to prepare modified asphalt binder. The chemical structure and morphology of rubber powder before and after activation and of asphalt binder before and after modification were characterized by Fourier transformation infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). The conventional and rheological properties and storage stability were analyzed to reveal the influence of activation method on the performance of asphalt binder. The results showed that after being activated, the surface of the rubber is loose and rough. A chemical reaction did not occur during activation by polyamide but occurred during activation by acrylamide. The activation of the rubber effectively improved the high- and low-temperature performance, and the softening difference decreased by 79.8%. This is because the interaction between rubber and asphalt binder was enhanced through activation of rubber, and grafting activation had better effect due to the chemical reaction between the basic amide groups of acrylamide and acid groups of asphalt binder.

Investigation on Rheological Properties and Storage Stability of Modified Asphalt Based on the Grafting Activation of Crumb Rubber.

Acrylamide with a double bond and amide group can not only copolymerize with macromolecules of crumb rubber but also react with acidic groups in asphalt, so it was selected as a modifier to activate crumb rubber through chemical graft action. The purpose is to improve the compatibility between crumb rubber and asphalt and thus improve the rheological properties and storage stability of rubber asphalt. Infrared spectroscopy (IR) and scanning electron microscopy (SEM) were used to characterize the crumb rubbers and their modified asphalt. It was found that the crumb rubber of grafting acrylamide had better compatibility in asphalt due to its larger specific surface area and chemical reaction with asphalt. In addition, the high temperature rheological test, low temperature creep test, and polymer separation test were carried out to study the effect of grafted activated crumb rubber on the properties of modified asphalt. The results showed that compared with modified asphalt with common crumb rubber (CRMA), the rheological properties and storage stability of modified asphalt with grafting activated crumb rubber (A-G-R) were improved significantly. The results of microscopic and macroscopic tests show that the activated rubber particles have a larger contact area with asphalt due to a rougher surface and the chemical cross-linking between rubber particles and asphalt further strengthens their interaction. Therefore, there is a relatively stable blend system formed in modified asphalt, and its performance of modified asphalt has been improved.

Investigation on Preparation Process and Storage Stability of Modified Asphalt Binder by Grafting Activated Crumb Rubber.

According to the theory of molecular design, crumb rubber was grafting activated with acrylamide and then used as asphalt binder modifier. An orthogonal three-factor, three-level test was designed to optimize the preparation process of modified asphalt. Softening point, viscosity, rutting factor, ductility, stiffness modulus and creep speed index were selected as evaluation indicators to study the effects of rubber content, shear time and shear temperature by variance analysis and range analysis. The results show that the rubber content had a significant impact on the performance of modified asphalt with grafting-activated crumb rubber, while the shear temperature and shear time had little effect. The grafting activated crumb rubber content of 20%, shear temperature of 170-190 °C, and shear time of 90 min was determined as the reasonable preparation process. Modified asphalt with common crumb rubber (CRMA) and modified asphalt with grafting activated crumb rubber (A-G-R) were prepared, respectively, using the reasonable process to analyze the influence of grafting activation of crumb rubber. The results indicate that A-G-R had smaller softening point difference, lower segregation index and more stable and uniform dispersed phase.

Effect of the micro-flocculation stage on the flocculation/sedimentation process: The role of shear rate.

Dynamic analysis on the variation of particle size distribution (PSD) and the fractal characteristics of PSD (Df) were investigated to better understand the continuous procedure of the floc growth and optimize the control of flocculation process. It was found that the flocculation process could be divided into three stages, i.e., the micro-flocculation stage, the growth stage and the steady (or breakage) stage. As the stage which is crucial to the morphology of micro-flocs (the building blocks of large flocs), the micro-flocculation stage plays an important role on flocculation/sedimentation process. The results showed that an increase in shear rate (11s-1

Characterization of re-grown floc size and structure: effect of mixing conditions during floc growth, breakage and re-growth process.

The impact of mixing speed in three stages-before breakage, during breakage, and after breakage-on re-grown floc properties was investigated by using a non-intrusive optical sampling and digital image analysis technique, respectively. And then, on the basis of different influence extent of mixing speed during each stage on size and structure of re-grown flocs, coagulation performance with varying mixing speed was analyzed. The results indicated that the broken flocs could not re-grow to the size before breakage in all cases. Furthermore, increasing mixing intensity contributed to the re-formation of smaller flocs with higher degree of compactness. For slow mixing before breakage, an increase in mixing speed had less influence on re-grown floc properties due to the same breakage strength during breakage, resulting in inconspicuous variation of coagulation efficiency. For rapid mixing during breakage, larger mixing speed markedly decreased the coagulation efficiency. This could be attributed that mixing speed during breakage generated greater influence on re-grown floc size. However, as slow mixing after breakage was elevated, the coagulation efficiency presented significant rise, indicating that slow mixing after breakage had more influence on re-grown floc structure upon re-structuring and re-arrangement mechanism.

Gelsolin-Like Domain 3 Plays Vital Roles in Regulating the Activities of the Lily Villin/Gelsolin/Fragmin Superfamily.

The villin/gelsolin/fragmin superfamily is a major group of Ca2+-dependent actin-binding proteins (ABPs) involved in various cellular processes. Members of this superfamily typically possess three or six tandem gelsolin-like (G) domains, and each domain plays a distinct role in actin filament dynamics. Although the activities of most G domains have been characterized, the biochemical function of the G3 domain remains poorly understood. In this study, we carefully compared the detailed biochemical activities of ABP29 (a new member of this family that contains the G1-G2 domains of lily ABP135) and ABP135G1-G3 (which contains the G1-G3 domains of lily ABP135). In the presence of high Ca2+ levels in vitro (200 and 10 µM), ABP135G1-G3 exhibited greater actin severing and/or depolymerization and nucleating activities than ABP29, and these proteins had similar actin capping activities. However, in the presence of low levels of Ca2+ (41 nM), ABP135G1-G3 had a weaker capping activity than ABP29. In addition, ABP29 inhibited F-actin depolymerization, as shown by dilution-mediated depolymerization assay, differing from the typical superfamily proteins. In contrast, ABP135G1-G3 accelerated F-actin depolymerization. All of these results demonstrate that the G3 domain plays specific roles in regulating the activities of the lily villin/gelsolin/fragmin superfamily proteins.

[Risk factors for capillary leak syndrome in children with hematological malignancies].

OBJECTIVE: To investigate the risk factors for capillary leak syndrome (CLS) in children with malignant hematologic diseases. METHODS: Thirty children with hematological malignancies complicated with CLS were analyzed with multiple logistic regression analysis. RESULTS: At the test level of 0.05, hypoxemia and septicemia were found to significantly correlate with CLS in these children, and the number of white blood cells before CLS and severe bone marrow suppression were near the test level. CONCLUSION: Hypoxemia and septicemia are risk factors for CLS in children with malignant hematologic diseases.

Implication of tumor stem-like cells in the tumorigenesis of sporadic paraganglioma.

It is commonly believed that paragangliomas are rare tumors arising from the neural crest-derived chromaffin cells. Although it has been speculated that paraganglioma is related to stem cell origin, there has been lack of direct evidence demonstrating the presence of (neural) stem cells in these tumor tissues. In this study, we found a subgroup of human paraganglioma from ten clinical samples displayed definitive markers of CD133 and/or nestin, the fundamental features of neural stem cell capable of self-renewal and differentiation. A panel of lineage-specific markers was also manifest in some of these tumors, consistent with the hierarchical and heterogeneous nature of these tumors. These observations strongly suggest that at least some forms of paraganglioma maintain tumor stem-like cells (TSCs) that potentially contribute to the histologic complexity of human paraganglioma. Finally, we found that the genomic DNA structure becomes highly unstable in tumor cells of paraganglioma, indicating the loss of tight control of genomic surveillance system be an important transitory event from normal multi-potent tissue stem cells to TSCs.

N-acetylcysteine improves pancreatic microcirculation and alleviates the severity of acute necrotizing pancreatitis.

BACKGROUND/AIMS: To investigate the beneficial effect of N-Acetylcysteine (NAC) on pancreatic microvascular perfusion in acute necrotizing pancreatitis (ANP). METHODS: Fifty-four rats were divided into a control group, an ANP group and an NAC-treated group. The ANP model was established by a retrograde injection of 3% sodium taurocholate into the pancreatic duct. The NAC-treated group received an intravenous infusion of NAC just 2 hours before and 30 minutes after the induction of ANP. The pancreatic microvascular perfusion was measured with laser Doppler flowmetry and pancreatic samples were collected for histological examination. RESULTS: The microvascular perfusion in the NAC-treated group decreased slightly and exhibited a significant increase compared to the ANP group (p<0.01). A pathological examination revealed that edema and inflammatory infiltration decreased, and the hemorrhaging and necrosis of the pancreas were significantly reduced. CONCLUSIONS: NAC could improve pancreatic microvascular perfusion and alleviate the severity of sodium taurocholate-induced ANP, possibly representing a new therapeutic approach to prevent the progression of ANP.