Analysis of blood methylation quantitative trait loci in East Asians reveals ancestry-specific impacts on complex traits.

Methylation quantitative trait loci (mQTLs) are essential for understanding the role of DNA methylation changes in genetic predisposition, yet they have not been fully characterized in East Asians (EAs). Here we identified mQTLs in whole blood from 3,523 Chinese individuals and replicated them in additional 1,858 Chinese individuals from two cohorts. Over 9% of mQTLs displayed specificity to EAs, facilitating the fine-mapping of EA-specific genetic associations, as shown for variants associated with height. Trans-mQTL hotspots revealed biological pathways contributing to EA-specific genetic associations, including an ERG-mediated 233 trans-mCpG network, implicated in hematopoietic cell differentiation, which likely reflects binding efficiency modulation of the ERG protein complex. More than 90% of mQTLs were shared between different blood cell lineages, with a smaller fraction of lineage-specific mQTLs displaying preferential hypomethylation in the respective lineages. Our study provides new insights into the mQTL landscape across genetic ancestries and their downstream effects on cellular processes and diseases/traits.

PheSeq, a Bayesian deep learning model to enhance and interpret the gene-disease association studies.

Despite the abundance of genotype-phenotype association studies, the resulting association outcomes often lack robustness and interpretations. To address these challenges, we introduce PheSeq, a Bayesian deep learning model that enhances and interprets association studies through the integration and perception of phenotype descriptions. By implementing the PheSeq model in three case studies on Alzheimer's disease, breast cancer, and lung cancer, we identify 1024 priority genes for Alzheimer's disease and 818 and 566 genes for breast cancer and lung cancer, respectively. Benefiting from data fusion, these findings represent moderate positive rates, high recall rates, and interpretation in gene-disease association studies.

Pulsed Ho:YLF laser intra-cavity pumped by a diode-pumped Q-switched Tm:YAP laser.

We reported an intra-cavity pumped Q-switched laser with dual-wavelength synchronous output at 2066.7 nm and 1940nm. Ho:YLF crystal was pumped by a self-Q-switched Tm:YAP laser, which was served as both a gain medium and a saturable absorber simultaneously. For Ho:YLF laser, under 11.4-W incident pump power, a stable pulse laser was achieved at 2066.7 nm with the highest peak power of 69.65 W and the pulse repetition rate of 42.14 kHz. Under the same incident pump power, the highest peak power and pulse repetition rate of Tm:YAP laser were 17.85 W and 50.82 kHz, corresponding to the central wavelength of 1940nm. These results suggested that Q-switching without additional absorber element were effective way to obtain high-efficiency and compact 2.1 µm pulsed laser.

Quality assessment of clinical practice guidelines for adult obstructive sleep apnea: A systematic review.

OBJECTIVE: Clinical Practice Guidelines (CPGs) are crucial in standardizing the management of obstructive sleep apnea (OSA) in adults. However, there has been insufficient evaluation of the overall quality of CPGs for adult OSA. This review aimed to comprehensively assess the overall quality of CPGs in the field of adult OSA. METHODS: A systematic search was conducted on various literature databases, guideline-related databases, and academic websites from January 2013 to December 2023 to select CPGs relevant to adult OSA. The methodological and reporting quality of the eligible CPGs were thoroughly appraised by three reviewers using the AGREE II instrument and RIGHT checklist, respectively. RESULTS: This review included 44 CPGs, consisting of 42 CPGs in English and 2 CPGs in Chinese. The assessment of methodological quality revealed that four domains attained an average standardized score above 60%. Among the domains, "clarity of presentation" received the highest standardized score of 85.10%, while the lowest standardized score was observed in the "rigor of development" domain with the value of 56.77%. The evaluation of reporting quality indicated an overall reporting rate of 51.30% for the eligible CPGs, with only three domains achieving an average reporting rate higher than 50%. The domain with the highest reporting rate was "basic information" at 60.61%, while the domain with the lowest reporting rate was "review and quality assurance" at 15.91%. Furthermore, a significantly positive correlation was found between the AGREE II standardized scores and the RIGHT reporting rates (r = 0.808, P < 0.001). CONCLUSIONS: The overall quality of the currently available guidelines for adult OSA demonstrated considerable variability. Researchers should prioritize the utilization of evidence-based methods and adhere to the items listed in the RIGHT checklist when developing CPGs to enhance efficient clinical decision-making and promote the translation of evidence into practice.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

The Schwann cell-specific G-protein Gαo (Gnao1) is a cell-intrinsic controller contributing to the regulation of myelination in peripheral nerve system.

Myelin sheath abnormality is the cause of various neurodegenerative diseases (NDDs). G-proteins and their coupled receptors (GPCRs) play the important roles in myelination. Gnao1, encoding the major Gα protein (Gαo) in mammalian nerve system, is required for normal motor function. Here, we show that Gnao1 restricted to Schwann cell (SCs) lineage, but not neurons, negatively regulate SC differentiation, myelination, as well as re-myelination in peripheral nervous system (PNS). Mice lacking Gnao1 expression in SCs exhibit faster re-myelination and motor function recovery after nerve injury. Conversely, mice with Gnao1 overexpression in SCs display the insufficient myelinating capacity and delayed re-myelination. In vitro, Gnao1 deletion in SCs promotes SC differentiation. We found that Gnao1 knockdown in SCs resulting in the elevation of cAMP content and the activation of PI3K/AKT pathway, both associated with SC differentiation. The analysis of RNA sequencing data further evidenced that Gnao1 deletion cause the increased expression of myelin-related molecules and activation of regulatory pathways. Taken together, our data indicate that Gnao1 negatively regulated SC differentiation by reducing cAMP level and inhibiting PI3K-AKT cascade activation, identifying a novel drug target for the treatment of demyelinating diseases.

Morphological and physiological response of amphibious Rotala rotundifolia from emergent to submerged form.

Rotala rotundifolia is an amphibious aquatic plant that can live in submerged and emergent forms. It is superior in nitrogen and phosphorus removal. To elucidate its adaptation strategies from emergent to submerged conditions, phenotypic and physiological responses of R. rotundifolia were investigated during three months of submergence, at water levels of 0 cm (CK), 50 cm (W50), and 90 cm (W90). Results showed that submergence stress reduced the relative growth rate of plant height, fresh weight, and biomass accumulation, leading to root degradation and a significant decline in the root-shoot ratio. The amounts of soluble protein (SP), soluble sugar (SS), and starch in the aerial leaves of W50 and W90 decreased during the early stages of submergence compared to CK, whereas the total chlorophyll and proline contents, and activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) increased. The contents of endogenous hormones, including abscisic acid (ABA), gibberellin (GA), and indole-3-acetic acid (IAA), decreased during the change in leaf shape; the decline in ABA was more obvious. The leaf primordium generated transition leaves and submerged leaves to resolve the "carbon starvation" of plants. The maximum values of non-structural carbohydrates (NSC) in the leaves of W50 and W90 occurred at day 30, reaching 14.0 mg g- 1and 10.5 mg g- 1, respectively. The contents of SP and starch, activities of SOD and CAT of the roots in submerged treatments increased, while SS and proline content decreased at day 7. These results demonstrated that developing heterophyllous leaves, increasing chlorophyll content, and regulating plant carbon allocation and consumption were important mechanisms of R. rotundifolia to adapt to underwater habitats.

Advances in the metabolic engineering of Saccharomyces cerevisiae and Yarrowia lipolytica for the production of ß-carotene.

ß-Carotene is one kind of the most important carotenoids. The major functions of ß-carotene include the antioxidant and anti-cardiovascular properties, which make it a growing market. Recently, the use of metabolic engineering to construct microbial cell factories to synthesize ß-carotene has become the latest model for its industrial production. Among these cell factories, yeasts including Saccharomyces cerevisiae and Yarrowia lipolytica have attracted the most attention because of the: security, mature genetic manipulation tools, high flux toward carotenoids using the native mevalonate pathway and robustness for large-scale fermentation. In this review, the latest strategies for ß-carotene biosynthesis, including protein engineering, promoters engineering and morphological engineering are summarized in detail. Finally, perspectives for future engineering approaches are proposed to improve ß-carotene production.

Constructing Carbon Nanotube-Enhanced Ultra-Thin Organic Compounds with Multi-Redox Sites for "All-Temperature" Potassium-Ion Battery Anode and its Step-Wise K-Storage Mechanism.

Organic compounds are regarded as important candidates for potassium-ion batteries (KIBs) due to their light elements, controllable polymerization, and tunable functional groups. However, intrinsic drawbacks largely restrict their application, including possible solubility in electrolytes, poor conductivity, and low diffusion coefficients. To address these issues, an ultrathin layered pyrazine/carbonyl-rich material (CT) is synthesized via an acid-catalyzed solvothermal reaction and homogeneously grown on carbon nanotubes (CNTs), marked as CT@CNT. Such materials have shown good features of exposing functional groups to guest ions and good electron transport paths, exhibiting high reversible capacity and remarkable rate capability over a wide temperature range. Two typical electrolytes are compared, demonstrating that the electrolyte of LX-146 is more suitable to maximize the electrochemical performances of electrodes at different temperatures. A stepwise reaction mechanism of K-chelating with C═O and C═N functional groups is proposed, verified by in/ex situ spectroscopic techniques and theoretical calculations, illustrating that pyrazines and carbonyls play the main roles in reacting with K+ cations, and CNTs promote conductivity and restrain electrode dissolution. This study provides new insights to understand the K-storage behaviors of organic compounds and their "all-temperature" application.

Preparation and SERS applications of Ta2O5 composite nanostructures.

Noble metal and semiconductor composite substrates possess high sensitivity, excellent stability, good biocompatibility, and selective enhancement, making them an important research direction in the field of surface-enhanced Raman scattering (SERS). Ta2O5, as a semiconductor material with high thermal stability, corrosion resistance, outstanding optical properties, and catalytic performance, has great potential in SERS research. This study aims to design and fabricate a composite SERS substrate based on Ta2O5 nanostructures, achieving optimal detection performance by combining the urchin-like structure of Ta2O5 with silver nanoparticles (Ag NPs). The urchin-like Ta2O5 nanostructures were prepared using a hydrothermal reaction method. The bandgap was modulated through structure design and the self-doping technique, the charge transfer efficiency and surface plasmon resonance effects were improved, thereby achieving better SERS performance. The composite substrate enables highly sensitive quantitative detection. This composite SERS substrate combines the electromagnetic enhancement mechanism (EM) and chemical enhancement mechanism (CM), achieving ultra-low detection limits of 10-13 M for R6G. Within the concentration range above 10-12 M, there is a good linear relationship between concentration and peak intensity, demonstrating excellent quantitative analysis capabilities. Furthermore, this composite SERS substrate is capable of precise detection of analytes such as crystal violet (CV) and methylene blue (MB), holding broad application prospects in areas such as food safety and environmental monitoring.

Suppressed Histone H3 Lysine 18 Acetylation Is Involved in Arsenic-Induced Liver Fibrosis in Rats by Triggering the Dedifferentiation of Liver Sinusoidal Endothelial Cells.

Arsenic pollution is a global environmental concern. Arsenic-induced chronic liver injury and its irreversible outcomes, including liver cirrhosis and liver cancer, threaten the health of residents in arsenic-contaminated areas. Liver fibrosis is a reversible pathological stage in the progression of arsenic-induced chronic liver injury to cirrhosis and liver cancer. The aim of this study is to identify the epigenetic mechanism of arsenic-induced liver fibrosis based on the dedifferentiation of liver sinusoidal endothelial cells (LSECs). Rats were treated with 0.0, 2.5, 5.0, or 10.0 mg/kg sodium arsenite for 36 weeks. Marked fibrotic phenotypes were observed in the rat livers, manifested by hepatic stellate cell activation and an increased extracellular matrix, as well as the deposition of collagen fibers. The reduced fenestrations on the cells' surface and the increased expression of the dedifferentiation marker CD31 corroborated the LSECs' dedifferentiation in the liver tissue, which was also found to be significantly associated with fibrotic phenotypes. We further revealed that arsenic exposure could inhibit the enrichment of histone H3 lysine 18 acetylation (H3K18ac) in the promoters of Fcgr2b and Lyve1, two key genes responsible for maintaining the differentiation phenotype of LSECs. This inhibition subsequently suppressed the genes' expression, promoting LSEC dedifferentiation and subsequent liver fibrosis. In conclusion, arsenic can trigger liver fibrosis by inhibiting H3K18ac-dependent maintenance of LSEC differentiation. These findings uncover a novel mechanism of arsenic-induced liver fibrosis based on a new insight into epigenetically dependent LSEC dedifferentiation.

The transcription factor Stat-1 is essential for Schwann cell differentiation, myelination and myelin sheath regeneration.

BACKGROUND: Myelin sheath is a crucial accessory to the functional nerve-fiber unit, its disruption or loss can lead to axonal degeneration and subsequent neurodegenerative diseases (NDs). Notwithstanding of substantial progress in possible molecular mechanisms underlying myelination, there is no therapeutics that prevent demyelination in NDs. Therefore, it is crucial to seek for potential intervention targets. Here, we focused on the transcriptional factor, signal transducer and activator of transcription 1 (Stat1), to explore its effects on myelination and its potential as a drug target. METHODS: By analyzing the transcriptome data obtained from Schwann cells (SCs) at different stages of myelination, it was found that Stat1 might be involved in myelination. To test this, we used the following experiments: (1) In vivo, the effect of Stat1 on remyelination was observed in an in vivo myelination mode with Stat1 knockdown in sciatic nerves or specific knockdown in SCs. (2) In vitro, the RNA interference combined with cell proliferation assay, scratch assay, SC aggregate sphere migration assay, and a SC differentiation model, were used to assess the effects of Stat1 on SC proliferation, migration and differentiation. Chromatin immunoprecipitation sequencing (ChIP-Seq), RNA-Seq, ChIP-qPCR and luciferase activity reporter assay were performed to investigate the possible mechanisms of Stat1 regulating myelination. RESULTS: Stat1 is important for myelination. Stat1 knockdown in nerve or in SCs reduces the axonal remyelination in the injured sciatic nerve of rats. Deletion of Stat1 in SCs blocks SC differentiation thereby inhibiting the myelination program. Stat1 interacts with the promoter of Rab11-family interacting protein 1 (Rab11fip1) to initiate SC differentiation. CONCLUSION: Our findings demonstrate that Stat1 regulates SC differentiation to control myelinogenic programs and repair, uncover a novel function of Stat1, providing a candidate molecule for clinical intervention in demyelinating diseases.

SCML2 contributes to tumor cell resistance to DNA damage through regulating p53 and CHK1 stability.

SCML2 has been found to be highly expressed in various tumors. However, the extent to which SCML2 is involved in tumorigenesis and cancer therapy is yet to be fully understood. In this study, we aimed to investigate the relationship between SCML2 and DNA damage response (DDR). Firstly, DNA damage stabilizes SCML2 through CHK1-mediated phosphorylation at Ser570. Functionally, this increased stability of SCML2 enhances resistance to DNA damage agents in p53-positive, p53-mutant, and p53-negative cells. Notably, SCML2 promotes chemoresistance through distinct mechanisms in p53-positive and p53-negative cancer cells. SCML2 binds to the TRAF domain of USP7, and Ser441 is a critical residue for their interaction. In p53-positive cancer cells, SCML2 competes with p53 for USP7 binding and destabilizes p53, which prevents DNA damage-induced p53 overactivation and increases chemoresistance. In p53-mutant or p53-negative cancer cells, SCML2 promotes CHK1 and p21 stability by inhibiting their ubiquitination, thereby enhancing the resistance to DNA damage agents. Interestingly, we found that SCML2A primarily stabilizes CHK1, while SCML2B regulates the stability of p21. Therefore, we have identified SCML2 as a novel regulator of chemotherapy resistance and uncovered a positive feedback loop between SCML2 and CHK1 after DNA damage, which serves to promote the chemoresistance to DNA damage agents.

High-Level Production of Patchoulol in Yarrowia lipolytica via Systematic Engineering Strategies.

Patchoulol is an important sesquiterpene alcohol with a strong and lasting odor, which has led to prominent applications in perfumes and cosmetics. In this study, systematic metabolic engineering strategies were adopted to create an efficient yeast cell factory for patchoulol overproduction. First, a baseline strain was constructed by selecting a highly active patchoulol synthase. Subsequently, the mevalonate precursor pool was expanded to boost patchoulol synthesis. Moreover, a method for downregulating squalene synthesis based on Cu2+-repressible promoter was optimized, which significantly improved the patchoulol titer by 100.9% to 124 mg/L. In addition, a protein fusion strategy resulted in a final titer of 235 mg/L in shake flasks. Finally, 2.864 g/L patchoulol could be produced in a 5 L bioreactor, representing a remarkable 1684-fold increase compared to the baseline strain. To our knowledge, this is the highest patchoulol titer reported so far.

Genetic Variants in Telomerase Reverse Transcriptase Contribute to Solar Lentigines.

Solar lentigines (SLs) are a hallmark of human skin aging. They result from chronic exposure to sunlight and other environmental stressors. Recent studies also imply genetic factors, but findings are partially conflicting and lack of replication. Through a multi-trait based analysis strategy, we discovered that genetic variants in telomerase reverse transcriptase were significantly associated with non-facial SL in two East Asian (Taizhou longitudinal cohort, n = 2,964 and National Survey of Physical Traits, n = 2,954) and one Caucasian population (SALIA, n = 462), top SNP rs2853672 (P-value for Taizhou longitudinal cohort = 1.32 × 10‒28 and P-value for National Survey of Physical Traits = 3.66 × 10‒17 and P-value for SALIA = 0.0007 and Pmeta = 4.93 × 10‒44). The same variants were nominally associated with facial SL but not with other skin aging or skin pigmentation traits. The SL-enhanced allele/haplotype upregulated the transcription of the telomerase reverse transcriptase gene. Of note, well-known telomerase reverse transcriptase‒related aging markers such as leukocyte telomere length and intrinsic epigenetic age acceleration were not associated with SL. Our results indicate a previously unrecognized role of telomerase reverse transcriptase in skin aging‒related lentigines formation.

High-yield α-humulene production in Yarrowia lipolytica from waste cooking oil based on transcriptome analysis and metabolic engineering.

BACKGROUND: α-Humulene is an important biologically active sesquiterpene, whose heterologous production in microorganisms is a promising alternative biotechnological process to plant extraction and chemical synthesis. In addition, the reduction of production expenses is also an extremely critical factor in the sustainable and industrial production of α-humulene. In order to meet the requirements of industrialization, finding renewable substitute feedstocks such as low cost or waste substrates for terpenoids production remains an area of active research. RESULTS: In this study, we investigated the feasibility of peroxisome-engineering strain to utilize waste cooking oil (WCO) for high production of α-humulene while reducing the cost. Subsequently, transcriptome analysis revealed differences in gene expression levels with different carbon sources. The results showed that single or combination regulations of target genes identified by transcriptome were effective to enhance the α-humulene titer. Finally, the engineered strain could produce 5.9 g/L α-humulene in a 5-L bioreactor. CONCLUSION: To the best of our knowledge, this is the first report that converted WCO to α-humulene in peroxisome-engineering strain. These findings provide valuable insights into the high-level production of α-humulene in Y. lipolytica and its utilization in WCO bioconversion.

Recent Development of Advanced Biotechnology in the Oleaginous Fungi for Arachidonic Acid Production.

Arachidonic acid is an essential ω-6 polyunsaturated fatty acid, which plays a significant role in cardiovascular health and neurological development, leading to its wide use in the food and pharmaceutical industries. Traditionally, ARA is obtained from deep-sea fish oil. However, this source is limited by season and is depleting the already threatened global fish stocks. With the rapid development of synthetic biology in recent years, oleaginous fungi have gradually attracted increasing attention as promising microbial sources for large-scale ARA production. Numerous advanced technologies including metabolic engineering, dynamic regulation of fermentation conditions, and multiomics analysis were successfully adapted to increase ARA synthesis. This review summarizes recent advances in the bioengineering of oleaginous fungi for ARA production. Finally, perspectives for future engineering approaches are proposed to further improve the titer yield and productivity of ARA.

Biomimetic, hierarchical-ordered cellulose nanoclaw hybrid aerogel with high strength and thermal insulation.

High-performance thermally insulating nanocellulose-based aerogels with robust mechanical properties is highly desirable for energy-saving and thermal protection applications. However, the large-scale applications of traditional nanocellulose aerogels are still limited by their brittleness nature and rigorous processes. Herein, an effective biomimetic hybrid strategy for high strength and thermal insulated nanocellulose-based aerogel with hierarchical-ordered microstructure is designed and fabricated. The novel cellulose nanoclaws-based aerogels extracted from corncob are hybridized by nanosized silica aerogel layer in situ and have an intensified H-bonding crosslinked network after ambient-drying and hotpress treatment, endowing excellent mechanical properties (16-58 MPa) as well as scalable potential for structure materials. Benefitting from the synergistic effect of the tailored hierarchical-ordered microstructure, the resulting hybrid aerogels also possess high specific surface area (30-630 m2 g-1), low thermal conductivity (0.021 W m-1 K-1), and outstanding flame retardant. This hybrid strategy provides an avenue to produce thermal-insulated and mechanically robust materials.

[Characteristics and Health Risk Assessment of Trace Elements in Atmospheric PM1 During Autumn and Winter in Qingdao].

From November 1,2018 to January 31,2019 (OP2018-2019) and from November 1,2019 to January 20, 2020 (OP2019-2020), PM1 measurement was conducted daily for two consecutive years. The concentration of trace elements in the atmospheric PM1 in Qingdao in autumn and winter was analyzed. The observation period was divided into four air quality levels (Level Ⅰ, Level Ⅱ, Level Ⅲ, and Level Ⅳ), and the characteristics and sources of the concentration of trace elements in PM1 were analyzed. The non-carcinogenic risks (Zn, Pb, Mn, Cu, and V) and carcinogenic risks (As, Cr, Ni, Cd, and Co) of different people with different air quality levels were evaluated. The results showed that the changes in total metal element concentrations were associated with changes in Ca, K, and Al concentrations at different air quality classes during OP2019-2020 compared to those during OP2018-2019 and were more influenced by dust and biomass combustion sources. Compared with that during OP2018-2019, the V concentration in different air quality levels (Level Ⅰ, Level Ⅱ, Level Ⅲ, and Level Ⅳ) during OP2019-2020 decreased by 19.0%, 60.5%, 82.7%, and 77.5%, respectively. This was presumed to be related to the implementation of the Domestic Emission Control Area (DECA) policy for ships, which led to the significant reduction in V concentration due to the change in fuel quality of ships in the waters around Qingdao. The results of the enrichment factor, the ratio method, and the backward trajectory of airflow further indicated that the changes in V concentrations were mainly influenced by the DECA policy. However, after the implementation of the DECA, the V/Ni value as a limit for judging the influence of ship sources in the area required further exploration. The health risk assessment results showed that the risk factor of Mn ranged from 0.07 to 1.22 during OP2018-2019 and OP2019-2020. It was recommended to strengthen the management and control of Mn-containing pollution sources. The lifetime carcinogenic risk (ILCR) value of As and Cd under different air qualities during OP2018-2019 and OP2019-2020 was lower than 10-4 but higher than 10-6, indicating that there was a carcinogenic probability, although it was still at an acceptable level. During OP2018-2019, when the air quality was Ⅳ, the ILCR value of Cr was higher than 10-4, and there was a risk of cancer.

Establishment of relapse risk model and multivariate logistic regression analysis on risk factors of relapse in children with primary nephrotic syndrome.

This study aimed to investigate relapse risk factors in children with primary nephrotic syndrome (PNS) for prevention and early intervention via logistic regression. One hundred thirty-seven children with PNS were enrolled in this study. Clinical variables were analyzed by single-factor and multiple regression analysis to establish the regression equation. The predictive ability of the regression equation was investigated by the receiver operating characteristic curve (ROC). Files of 17 patients were lost, and 120 patients were enrolled finally in the study, among whom 55 cases (45.8%) had frequently relapsed. Single-factor analysis and multiple regression analysis revealed that concurrent infection on first onset, irregular glucocorticoid therapy, severe hypoalbuminemia, and persistent severe hyperlipidemia were the significant risk factors for frequent relapse on PNS (P < .05), among which infection remained to be the main inductive factor. Among the 4 indicators, serum albumin had the best diagnostic efficacy based on the area under the ROC curve (0.933), sensitivity (89.09%), and specificity (81.54%). The area under curve, sensitivity, and specificity for the combined diagnostic model of the 4 indices were 97.8%, 98.18%, and 90.77%, respectively, which had good predictive power for the relapse of patients. Concurrent infection, irregular glucocorticoid therapy, severe hypoalbuminemia, and persistent severe hyperlipemia were all the risk factors for PNS relapse. The established logistic regression model based on these factors above is reliable for predicting frequent PNS relapse. Much attention should be paid to these critical factors, and early intervention should be taken to reduce the incidence of relapse.