Exploring Symptom Clusters in Chinese Patients with Diabetic Kidney Disease: A Network Analysis.

Purpose: The research on symptom management in patients with diabetic kidney disease (DKD) has shifted from separate symptoms to symptom clusters and networks recently. This study aimed to evaluate the unpleasant symptoms of DKD patients, and to investigate how these symptom clusters could affect patients. Methods: 408 DKD patients were recruited in this cross-sectional study. The symptoms of DKD patients were measured using the modified Dialysis Symptom Index. Network analysis was employed to evaluate the symptom network and the characteristics of individual nodes, while factor analysis was utilized to identify symptom clusters. Results: Blurred vision was the most prevalent symptom among DKD patients. The symptoms identified as the most distressing, severe, and frequent were light headache or dizziness, arteriovenous fistula/catheterization pain, and diarrhea, respectively. Five symptom clusters were obtained from factor analysis, and the most central symptom cluster in the entire symptom network was sexual dysfunction. Conclusion: This study identified five symptom clusters in Chinese DKD patients, with sexual dysfunction emerging as the most central cluster. These findings carry significant clinical implications, underscoring the necessity of assessing symptom clusters and their associations to enhance symptom management in DKD patients. Further research is essential to elucidate the underlying mechanisms of symptoms and to clarify the associations among symptoms in DKD patients across different disease trajectories or treatment modalities.

One-year trajectories of nutritional status in perimenopausal women: a community-based multi-centered prospective study.

BACKGROUND: Nutritional status is a modifiable factor associated with perimenopausal women's health and quality of life. Assessing body composition indicators helps to comprehensively understand nutritional status compared with using body mass index (BMI) only. However, few published studies measured the trends in body composition among perimenopausal women. OBJECTIVES: To assess the one-year trajectory of the nutritional status of perimenopausal women and to explore its influential factors. METHODS: A community-based observational study with 3-wave repeated measurements at 6-month intervals was carried out. The nutritional status indicators include weight, body mass index (BMI), and body composition variables. Bioelectrical impedance analysis was used to assess body composition. Repeated measures ANOVA and Chi-square test were used to calculate the changes in nutritional status and generalized estimating equations were performed to explore their influential factors. RESULTS: 2760 participants completed the study. Increasing trajectories in weight (from 56.05 ± 7.55 to 57.02 ± 7.60), fat mass (from 17.99 ± 4.80 to 20.49 ± 4.90), and waist-hip ratio (from 0.86 ± 0.04 to 0.91 ± 0.15) were found (P < 0.001). Decreasing trajectories in skeletal muscle (from 20.30 ± 2.38 to 19.19 ± 2.46), protein level (from 7.39 ± 0.79 to 7.06 ± 0.81), and total body water (from 27.87 ± 2.92 to 27.00 ± 3.01) were found (P < 0.001). Being married/unmarried with a partner and without negative life events were associated with higher total body water, skeletal muscle, and protein level, while negatively associated with fat mass and waist-hip ratio. Age was positively associated with fat mass (P < 0.001). Participants with junior high school education were prone to increased fat mass (P = 0.018) compared with those holding primary school education and below. A per capita monthly income of 1500 to 3000 Yuan was associated with higher total body water, skeletal muscle, and protein level (P < 0.001) compared with a per capita monthly income of less than 1500 Yuan. CONCLUSION: Worsening nutritional status exists in perimenopausal women, which is characterized by increased weight, fat mass, and waist-hip ratio, and decreased skeletal muscle, total body water, and protein level. For greater efficiency, precision nutritional interventions are needed, and recipients should be classified into different risk levels based on their sociodemographic background.

A novel IgE epitope-specific antibodies-based sandwich ELISA for sensitive measurement of immunoreactivity changes of peanut allergen Ara h 2 in processed foods.

Background: Peanut is an important source of dietary protein for human beings, but it is also recognized as one of the eight major food allergens. Binding of IgE antibodies to specific epitopes in peanut allergens plays important roles in initiating peanut-allergic reactions, and Ara h 2 is widely considered as the most potent peanut allergen and the best predictor of peanut allergy. Therefore, Ara h 2 IgE epitopes can serve as useful biomarkers for prediction of IgE-binding variations of Ara h 2 and peanut in foods. This study aimed to develop and validate an IgE epitope-specific antibodies (IgE-EsAbs)-based sandwich ELISA (sELISA) for detection of Ara h 2 and measurement of Ara h 2 IgE-immunoreactivity changes in foods. Methods: DEAE-Sepharose Fast Flow anion-exchange chromatography combining with SDS-PAGE gel extraction were applied to purify Ara h 2 from raw peanut. Hybridoma and epitope vaccine techniques were employed to generate a monoclonal antibody against a major IgE epitope of Ara h 2 and a polyclonal antibody against 12 IgE epitopes of Ara h 2, respectively. ELISA was carried out to evaluate the target binding and specificity of the generated IgE-EsAbs. Subsequently, IgE-EsAbs-based sELISA was developed to detect Ara h 2 and its allergenic residues in food samples. The IgE-binding capacity of Ara h 2 and peanut in foods was determined by competitive ELISA. The dose-effect relationship between the Ara h 2 IgE epitope content and Ara h 2 (or peanut) IgE-binding ability was further established to validate the reliability of the developed sELISA in measuring IgE-binding variations of Ara h 2 and peanut in foods. Results: The obtained Ara h 2 had a purity of 94.44%. Antibody characterization revealed that the IgE-EsAbs recognized the target IgE epitope(s) of Ara h 2 and exhibited high specificity. Accordingly, an IgE-EsAbs-based sELISA using these antibodies was able to detect Ara h 2 and its allergenic residues in food samples, with high sensitivity (a limit of detection of 0.98 ng/mL), accuracy (a mean bias of 0.88%), precision (relative standard deviation < 16.50%), specificity, and recovery (an average recovery of 98.28%). Moreover, the developed sELISA could predict IgE-binding variations of Ara h 2 and peanut in foods, as verified by using sera IgE derived from peanut-allergic individuals. Conclusion: This novel immunoassay could be a user-friendly method to monitor low level of Ara h 2 and to preliminary predict in vitro potential allergenicity of Ara h 2 and peanut in processed foods.

Characteristics of gut bacterial microbiota of black soldier fly (Diptera: Stratiomyidae) larvae effected by typical antibiotics.

As agents in an emerging technology, Hermetia illucens (Linnaeus, 1758) (Diptera: Stratiomyidae) larvae, black soldier fly, have shown exciting potential for degrading antibiotics in organic solid waste, a process for which gut microorganisms play an important role. This study investigated the characteristics of larval gut bacterial communities effected by typical antibiotics. Initially, antibiotics significantly reduced the diversity of gut bacterial species. After 8 days, diversity recovered to similar to that of the control group in the chlortetracycline, tylosin, and sulfamethoxazole groups. Proteobacteria, Firmicutes, and Actinobacteriota were the dominant phyla at the initial BSFL gut. However, after 4 days treatment, the proportion of Actinobacteriota significantly decreased, but Bacteroidota notably increased. During the conversion process, 18, 18, 17, 21, and 19 core genera were present in the chlortetracycline, sulfamethoxazole, tylosin, norfloxacin, and gentamicin groups, respectively. Pseudomonas, Actinomyces, Morganella, Providencia and Klebsiella might be the important genera with extraordinary resistance and degradation to antibiotics. Statistical analyses of COGs showed that antibiotics changed the microbial community functions of BSFL gut. Compared with the control group, (i) the chlortetracycline, sulfamethoxazole, and tylosin groups showed significant increase in the classification functions of transcription, RNA processing and modification，and so on, (ii) the norfloxacin and gentamicin groups showed significant increase in defense mechanisms and other functions. Note that we categorized the response mechanisms of these classification functions to antibiotics into resistance and degradation. This provides a new perspective to deeply understand the joint biodegradation behavior of antibiotics in environments, and serves as an important reference for further development and utilization of microorganisms-assisted larvae for efficient degradation of antibiotics.

Associations between problematic internet use, life satisfaction, and deliberate self-harm among Chinese adolescents: A multi-centered longitudinal study.

INTRODUCTION: Problematic Internet use (PIU), which is associated with deliberate self-harm (DSH), has become a common problem among adolescents. Life satisfaction (LS) may be able to mitigate the negative influences of PIU and DSH. But the longitudinal associations among them are yet to be well-researched. METHODS: A longitudinal study with three-wave data collection involving 6092 adolescents was carried out in China. PIU, LS, and DSH were assessed using the Young Internet Addiction Test, the Satisfaction with Life Scale, and the Deliberate Self-Harm Inventory Nine-Item Version, respectively. A cross-lagged model was used to analyze the longitudinal interactions between them. Generalized Estimating Equations were adopted to identify their influential factors. RESULTS: The prevalence of single DSH behaviors from wave 1 to wave 3 was 5.04%, 5.00%, and 4.67%, and the repeated DHS from wave 1 to wave 3 was 2.9%, 3.2%, and 3.4%, respectively. Bidirectional longitudinal predictive associations were revealed between PIU and LS (p＜0.001), and LS and DSH (p＜0.001). DSH could longitudinally predict PIU (p＜0.001). Gender and age were associated with PIU, LS, and DSH (p＜0.001), and PIU was influenced by ethnicity (p＜0.001). CONCLUSION: PIU and LS, LS and DSH were associated bidirectionally. Adolescents with more severe DSH behaviors were inclined to become addicted to the Internet, and adolescents with a history of DSH had a higher risk of recurring DSH. Parents, schools, and administrators need to improve the LS of adolescents, with a particular focus on older, female adolescents.

Extraction of Chitin from Black Soldier Fly (Hermetia illucens) and Its Puparium by Using Biological Treatment.

Chitin is the second-largest natural polymer polysaccharide in nature. Due to its important physical and chemical properties and excellent biocompatibility, safety, and biodegradability, it is widely used in agriculture, medicine, food, environmental protection, and other fields. However, traditional extraction methods cause environmental pollution and damage the structure of chitin. Bioprocessing is an emerging technology that shows great potential. In this research, the puparia and adults of black soldier fly (BSF) (Hermetia illucens L.) were used as raw materials. A continuous fermentation method was designed to extract chitin, by using Bacillus subtilis S4 and Acetobacter pasteurianus AS1.41. The Fourier transform infrared spectroscopy identification results showed that the extracted sample was α-chitin. Under continuous fermentation conditions, the deproteinization (DP) rate, demineralization (DM) rate, chitin yield (CY), and deacetylation degree (DD) of puparium chitin were 33.33%, 94.92%, 59.90%, and 18.52%, respectively. Meanwhile, the DP rate, DM rate, CY, and DD of adult chitin were 46.63%, 90.93%, 47.31%, and 37.38%, respectively. For BSF, B. subtilis S4 had a certain DP ability, and A. pasteurianus AS1.41 had a good DM effect. Moreover, BSF at different developmental stages could affect CY, and a higher concentration of NaOH was more favorable for deacetylation. Overall, simultaneous continuous fermentation could be a new biological approach to extract chitin from BSF.

Longitudinal associations between sleep quality and menopausal symptoms among community-dwelling climacteric women: A multi-centered study.

STUDY OBJECTIVES: Menopausal symptoms exist in most climacteric women, which can harm the quality and satisfaction of life for them. Moreover, a series of ineluctable negative life changes experienced in middle-age usually make the situation more complicated and stressful. We aimed to determine the trajectories and influential factors of sleep quality and menopausal symptoms and their longitudinal interrelationships among climacteric women. METHODS: A total of 1875 community-dwelling climacteric women were included in this study. The Pittsburgh Sleep Quality Index (PSQI) and the Menopause Rating Scale (MRS) were adopted to assess sleep quality and menopausal symptoms, respectively. Data were collected 4 times from March 2019 to December 2019, at a 3-month interval. RESULTS: The Cross-lagged analysis showed that worse sleep quality and more severe menopausal symptoms over time after controlling for specified covariates, and more severe menopausal symptoms were predicted by declined sleep quality. The Generalized estimation equation model showed that education level, marital status, chronic diseases, life events, income, and age were the influential factors of sleep quality, while menopausal symptoms were impacted by marital status and income. CONCLUSIONS: Increasing negative sleep quality and more severe menopausal symptoms over time contribute to the health burden of climacteric women. Menopausal symptoms could be alleviated by sleep quality improvement, which is influenced by education level, marital status, chronic diseases, life events, age, and economic factors.

Promoting healthy lifestyle considerations during pregnancy in Midwifery clinics in China: a best practice implementation project.

OBJECTIVES: The aim of this project was to initiate and promote formal and individualized evidence-based education on healthy lifestyle choices during pregnancy for pregnant women. INTRODUCTION: Evidence suggests that lifestyle choices during pregnancy can have a profound influence on many pregnancy complications and chronic diseases such as preterm birth, diabetes, obesity, fetal growth restriction, breast cancer and hypertensive diseases in both pregnant women and their babies. It is widely accepted that formal, individualized, hospital-directed education about lifestyle choices during pregnancy should commence as early as the first consultation between pregnant women and maternal healthcare workers. METHODS: The methods of this project were audit and feedback. The approach to data collection used the Joanna Briggs Institute (JBI) Practical Application of Clinical Evidence System and implementation planning utilized the Getting Research into Practice component. A baseline audit of 50 observations of midwife-led education on prenatal lifestyle were conducted and measured against seven best practice audit criteria. Targeted strategies were then implemented to improve compliance to best practice. A follow-up audit was conducted over a 6-month period from June 2019 to November 2019. RESULTS: The baseline audit revealed significant deficits between current prenatal education practice and recommended best practice. Zero percent compliance was observed in six out of seven audit criteria, indicating that education provided did not conform to best practice. Total compliance (100%) was observed for one audit criterion at baseline, assessing pregnant women being offered an opportunity to discuss and ask questions regarding the education session or information they had received. Three barriers that prevented midwives from achieving compliance with best practice were identified, and a bundled education strategy was implemented. A follow-up audit indicated 100% compliance of all audit criteria. CONCLUSION: Results demonstrated that formal, individualized, midwife-led prenatal education and provision of relevant evidence-based resources had an immediate positive effect. The project helped to transform care givers' attitudes toward education regarding lifestyle during pregnancy from a passive routine 'must do' task to an active process with focus on healthy lifestyle and engagement of pregnant women. Future strategies such as support from hospital management and social media are planned in conjunction with follow-up clinical audits to ensure sustainability.

Nuclear Receptor Binding Protein 2 Is Downregulated in Medulloblastoma, and Reduces Tumor Cell Survival upon Overexpression.

Pseudokinases, comprising 10% of the human kinome, are emerging as regulators of canonical kinases and their functions are starting to be defined. We previously identified the pseudokinase Nuclear Receptor Binding Protein 2 (NRBP2) in a screen for genes regulated during neural differentiation. During mouse brain development, NRBP2 is expressed in the cerebellum, and in the adult brain, mainly confined to specific neuronal populations. To study the role of NRBP2 in brain tumors, we stained a brain tumor tissue array for NRPB2, and find its expression to be low, or absent, in a majority of the tumors. This includes medulloblastoma (MB), a pediatric tumor of the cerebellum. Using database mining of published MB data sets, we also find that NRBP2 is expressed at a lower level in MB than in the normal cerebellum. Recent studies indicate that MB exhibits frequent epigenetic alternations and we therefore treated MB cell lines with drugs inhibiting DNA methylation or histone deacetylation, which leads to an upregulation of NRBP2 mRNA expression, showing that it is under epigenetic regulation in cultured MB cells. Furthermore, forced overexpression of NRBP2 in MB cell lines causes a dramatic decrease in cell numbers, increased cell death, impaired cell migration and inhibited cell invasion in vitro. Taken together, our data indicate that downregulation of NRBP2 may be a feature by which MB cells escape growth regulation.

Involvement of Heparan Sulfate and Heparanase in Neural Development and Pathogenesis of Brain Tumors.

Brain tumors are aggressive and devastating diseases. The most common type of brain tumor, glioblastoma (GBM), is incurable and has one of the worst five-year survival rates of all human cancers. GBMs are invasive and infiltrate healthy brain tissue, which is one main reason they remain fatal despite resection, since cells that have already migrated away lead to rapid regrowth of the tumor. Curative therapy for medulloblastoma (MB), the most common pediatric brain tumor, has improved, but the outcome is still poor for many patients, and treatment causes long-term complications. Recent advances in the classification of pediatric brain tumors reveal distinct subgroups, allowing more targeted therapy for the most aggressive forms, and sparing children with less malignant tumors the side-effects of massive treatment. Heparan sulfate proteoglycans (HSPGs), main components of the neurogenic niche, interact specifically with a large number of physiologically important molecules and vital roles for HS biosynthesis and degradation in neural stem cell differentiation have been presented. HSPGs are composed of a core protein with attached highly charged, sulfated disaccharide chains. The major enzyme that degrades HS is heparanase (HPSE), an important regulator of extracellular matrix (ECM) remodeling which has been suggested to promote the growth and invasion of other types of tumors. This is of clinical interest because GBM are highly invasive and children with metastatic MB at the time of diagnosis exhibit a worse outcome. Here we review the involvement of HS and HPSE in development of the nervous system and some of its most malignant brain tumors, glioblastoma and medulloblastoma.

Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation.

Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage. Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly than WT ES cells in culture and formed larger teratomas in vivo. In addition, differentiating Hpse-Tg ES cells also had a higher growth rate, and overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a two-step, monolayer differentiation, we observed an increase in HPSE as wild-type (WT) ES cells differentiated into neural stem and progenitor cells followed by down-regulation of HPSE as these NSPCs differentiated into mature cells of the neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more oligodendrocytes than WT cultures, with a concomitant reduction in the number of neurons. Our present findings emphasize the importance of HS, in neural differentiation and suggest that by regulating the availability of growth factors and, or other macromolecules, HPSE promotes differentiation into oligodendrocytes.

Heparanase Promotes Glioma Progression and Is Inversely Correlated with Patient Survival.

Malignant glioma continues to be fatal, despite improved insight into its underlying molecular mechanisms. The most malignant form, glioblastoma (GBM), is characterized by aberrant activation of receptor tyrosine kinases (RTK) and infiltrative growth. Heparan sulfate proteoglycans (HSPG), integral components of the extracellular matrix of brain tumors, can regulate activation of many RTK pathways. This prompted us to investigate heparanase (HPSE), which cleaves HSPGs, for its role in glioma. This hypothesis was evaluated using tissue microarrays, GBM cells derived from patients, murine in vitro and in vivo models of glioma, and public databases. Downregulation of HPSE attenuated glioma cell proliferation, whereas addition of HPSE stimulated growth and activated ERK and AKT signaling. Using HPSE transgenic and knockout mice, it was demonstrated that tumor development in vivo was positively correlated to HPSE levels in the brain. HPSE also modified the tumor microenvironment, influencing reactive astrocytes, microglia/monocytes, and tumor angiogenesis. Furthermore, inhibition of HPSE reduces tumor cell numbers, both in vitro and in vivo HPSE was highly expressed in human glioma and GBM cell lines, compared with normal brain tissue. Indeed, a correlation was observed between high levels of HPSE and shorter survival of patients with high-grade glioma. In conclusion, these data provide proof-of-concept for anti-HPSE treatment of malignant glioma, as well as novel insights for the development of HPSE as a therapeutic target. IMPLICATIONS: This study aims to target both the malignant brain tumor cells per se and their microenvironment by changing the level of an enzyme, HPSE, that breaks down modified sugar chains on cell surfaces and in the extracellular space. Mol Cancer Res; 14(12); 1243-53. ©2016 AACR.

Utilizing the Dog Genome in the Search for Novel Candidate Genes Involved in Glioma Development-Genome Wide Association Mapping followed by Targeted Massive Parallel Sequencing Identifies a Strongly Associated Locus.

Gliomas are the most common form of malignant primary brain tumors in humans and second most common in dogs, occurring with similar frequencies in both species. Dogs are valuable spontaneous models of human complex diseases including cancers and may provide insight into disease susceptibility and oncogenesis. Several brachycephalic breeds such as Boxer, Bulldog and Boston Terrier have an elevated risk of developing glioma, but others, including Pug and Pekingese, are not at higher risk. To identify glioma-associated genetic susceptibility factors, an across-breed genome-wide association study (GWAS) was performed on 39 dog glioma cases and 141 controls from 25 dog breeds, identifying a genome-wide significant locus on canine chromosome (CFA) 26 (p = 2.8 x 10-8). Targeted re-sequencing of the 3.4 Mb candidate region was performed, followed by genotyping of the 56 SNVs that best fit the association pattern between the re-sequenced cases and controls. We identified three candidate genes that were highly associated with glioma susceptibility: CAMKK2, P2RX7 and DENR. CAMKK2 showed reduced expression in both canine and human brain tumors, and a non-synonymous variant in P2RX7, previously demonstrated to have a 50% decrease in receptor function, was also associated with disease. Thus, one or more of these genes appear to affect glioma susceptibility.

Heparan sulfate in the regulation of neural differentiation and glioma development.

Heparan sulfate proteoglycans (HSPGs) are the main components of the extracellular matrix, where they interact with a large number of physiologically important macromolecules. The sulfation pattern of heparan sulfate (HS) chains determines the interaction potential of the proteoglycans. Enzymes of the biosynthetic and degradation pathways for HS chains are thus important regulators in processes ranging from embryonic development to tissue homeostasis, but also for tumor development. Formation of the nervous system is also critically dependent on intact HSPGs, and several studies have outlined the role of HS in neural induction from embryonic stem cells. High-grade glioma is the most common malignant primary brain tumor among adults, and the outcome is poor. Neural stem cells and glioma stem cells have several common traits, such as sustained proliferation and a highly efficient migratory capacity in the brain. There are also similarities between the neurogenic niche where adult neural stem cells reside, and the tumorigenic niche. These include interactions with the extracellular matrix, and many of the matrix components are deregulated in glioma, e.g. HSPGs and enzymes implementing the biosynthesis and modification of HS. In this article, we will present how HS-regulated pathways are involved in neural differentiation, and discuss their impact on brain development. We will also review and critically discuss the important role of structural modifications of HS in glioma growth and invasion. We propose that targeting invasive mechanisms of glioma cells through modulation of HS structure and HS-mediated pathways may be an attractive alternative to other therapeutic attempts, which so far have only marginally increased survival for glioma patients.

Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication.

The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci.

[The transcriptional regulation study on human delta globin gene with CAAT box C-->T point mutation in its promoter].

OBJECTIVE: To study the transcriptional regulation of human delta globin gene with C-->T point mutation at -64 in its promoter. METHODS: Human delta globin genes including wild CAAT box and mutant CAAT box (-64C-->T) were separately cloned into eukaryotic expression vector pcDNA3.1 (-)/Myc-His A which was cut out the strong promoter CMV, transfected MEL cells, and induced by DMSO to express. The transcriptional regulation of human delta globin gene was analysed using semi-quantitative RT-PCR. RESULTS: The expression level of human delta globin gene with mutant CAAT box was 2.2-fold as high as that with wild CAAT box. CONCLUSION: The defective CAAT box of human delta globin gene promoter region may be one of the major reasons for its low expression level.