[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy.

The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.

Doping Ferrocene-Based Conjugated Microporous Polymers with 7,7,8,8-Tetracyanoquinodimethane for Efficient Photocatalytic CO2 Reduction.

The design and synthesis of organic photocatalysts remain a great challenge due to their strict structural constraints. However, this could be mitigated by achieving structural flexibility by constructing permanent porosity into the materials. Conjugated microporous polymers (CMPs) are an emerging class of porous materials with an amorphous, three-dimensional network structure, which makes it possible to integrate the elaborate functional groups to enhance photocatalytic performance. Here, we report the synthesis of a novel CMP, named TAPFc-TFPPy-CMP, constructed by 1,1'3,3'-tetra(4-aminophenyl)ferrocene (TAPFc) and 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) monomers. The integration of the p-type dopant 7,7,8,8-tetracyanoquinodimethane (TCNQ) into the TAPFc-TFPPy-CMP improved the light adsorption performance, leading to a decrease in the optical bandgap from 2.00 to 1.43 eV. The doped CMP (TCNQ@TAPFc-TFPPy-CMP) exhibited promising catalytic activity in photocatalytic CO2 reduction under visible light, yielding 546.8 µmol g-1 h-1 of CO with a selectivity of 96% and 5.2 µmol g-1 h-1 of CH4. This represented an 80% increase in the CO yield compared to the maternal TAPFc-TFPPy-CMP. The steady-state photoluminescence (PL) and fluorescence lifetime (FL) measurements reveal faster carrier separation and transport after the doping. This study provides guidance for the development of organic photocatalysts for the utilization of renewable energy.

The intervention of cannabinoid receptor in chronic and acute kidney disease animal models: a systematic review and meta-analysis.

AIM: Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease. METHODS: PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury. RESULTS: The blockade or knockout of CB1 could significantly reduce blood urea nitrogen [SMD,- 1.67 (95% CI - 2.27 to - 1.07)], serum creatinine [SMD, - 1.88 (95% CI - 2.91 to - 0.85)], and albuminuria [SMD, - 1.60 (95% CI - 2.16 to - 1.04)] in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine [SMD, - 0.97 (95% CI - 1.83 to - 0.11)] and albuminuria [SMD, - 2.43 (95% CI - 4.63 to - 0.23)] in renal dysfunction animals compared with the control group. CONCLUSIONS: The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.

Corrigendum to "Differences in primary and secondary stroke prevention strategies for Chinese men and women" [Prev. Med. Rep. 33 (2023) 102219].

[This corrects the article DOI: 10.1016/j.pmedr.2023.102219.].

Crystalline, Porous Helicene Covalent Organic Frameworks.

Helicenes are a class of fascinating chiral helical molecules with rich chemistry developed continuously over the past 100 years. Their helical, conjugated, and twisted structures make them attractive for constructing molecular systems. However, studies over the past century are mainly focused on synthesizing helicenes with increased numbers of aromatic rings and complex heterostructures, while research on inorganic, organic, and polymeric helicene materials is still embryonic. Herein, we report the first examples of helicene covalent organic frameworks, i.e., [7]Helicene sp2 c-COF-1, by condensing [7]Helicene dialdehyde with trimethyl triazine via the C=C bond formation reaction under solvothermal conditions. The resultant [7]Helicene sp2 c-COF-1 exhibits prominent X-ray diffraction peaks and assumes a highly ordered 2D lattice structure originated from the twisted configuration of [7]Helicene unit. The C=C linked [7]Helicene sp2 c-COF-1 materials exhibited extended π conjugation and broadly tuned their absorption, emission, redox activity, photoconductivity, and light-emitting activity, demonstrating rich multifunctionalities and great potentials in developing various applications. This work opens a way to a new family of COFs as well as helicene materials, enabling the exploration of unprecedented π architectures and properties.

Dopant-Matrix Afterglow Systems: Manipulation of Room-Temperature Phosphorescence/Thermally Activated Delayed Fluorescence Afterglow Mechanism via Mismatch/Match of Intermolecular Charge Transfer between Dopants and Matrices.

Dopant-matrix organic afterglow materials exhibit ease of fabrication and intriguing functions in diverse fields. However, a deep and comprehensive understanding of their photophysical behaviors remains elusive. Here we report manipulation of a room-temperature phosphorescence/thermally activated delayed fluorescence (RTP/TADF) afterglow mechanism via the mismatch/match of intermolecular charge transfer between dopants and matrices. When dispersed in inert crystalline matrices, the luminescent dopants show RTP lifetimes up to 2 s. Interestingly, when suitable organic matrices are selected, the resultant dopant-matrix materials display a TADF-type afterglow under ambient conditions due to the formation of dopant-matrix intermolecular charge transfer complexes. Detailed studies reveal that reverse intersystem crossing from dopants' T1 states to charge transfer complexes' S1 states, which features a moderate kRISC of 101-102 s-1, is responsible for the emergence of a TADF-type organic afterglow in rigid crystalline matrices. Such less reported delicate photophysics reveals a new aspect of the excited state property in dopant-matrix afterglow systems.

Identification of Serum Biomarkers of Ischemic Stroke in a Hypertensive Population Based on Metabolomics and Lipidomics.

Hypertensive individuals are at a high risk of stroke, and thus, prevention of stroke in hypertensive patients is essential. Metabolomics and lipidomics can be used to identify diagnostic biomarkers and conduct early assessments of stroke risk in hypertensive populations. In this study, serum samples were collected from 30 hypertensive ischemic stroke (IS), 30 matched hypertensive and 30 matched healthy participants. Metabolomics and lipidomics analyses were conducted via liquid chromatography-tandem mass spectrometry, and the data were analyzed using multivariate and univariate statistical methods. A random forest algorithm and binary logistic regression were used to screen the biomarkers and establish diagnostic model. We detected 21 differential metabolites and 38 differential lipids between the hypertensive IS and healthy group. Moreover, we found 18 differential metabolites and 31 differential lipids between the hypertensive IS and hypertension group. In particular, the following seven metabolites or lipids distinguished the hypertensive IS from the healthy group: 4-hydroxyphenylpyruvic acid, cafestol, phosphatidylethanolamine (PE) (18:0p/18:2), PE (16:0e/20:4), (O-acyI)-1-hydroxy fatty acid (36:3), PE (16:0p/20:3) and PE (18:1p/18:2) (rep). The following seven biomarkers distinguished the hypertensive IS from the hypertension group: diglyceride (DG) (20:1/18:2), PE (18:0p/18:2), PE (16:0e/22:5), phosphatidylcholine (40:7), dimethylphosphatidylethanolamine (50:3), DG (18:1/18:2), and 4-hydroxyphenylpyruvic acid. The aforementioned panels had good diagnostic and predictive ability for hypertensive IS. Our study determines the metabolomic and lipidomic profiles of hypertensive IS patients and thereby identifies potential biomarkers of the presence of IS in hypertensive populations.

Conjugated Microporous Polymers Based on Octet and Tetratopic Linkers for Efficient Iodine Capture.

Radioactive iodine from nuclear waste poses a huge threat to public safety and raises concerns about environmental pollution. There is thus a growing demand for developing novel adsorbents for highly effective iodine capture. In this work, we design and synthesize three novel conjugated microporous polymers, namely, TPE-PyTTA-CMP, TPE-TAPP-CMP, and TPE-TPDA-CMP, which are constructed by an imidization reaction based on octet and tetratopic linkers. The iodine vapor adsorption experiments show that the three CMPs have an excellent iodine adsorption capacity as high as 3.10, 3.67, and 4.68 g·g-1 under 348 K and ambient pressure conditions, respectively. The adsorbed iodine in the CMPs can be released into methanol in a dramatically rapid manner, and their excellent iodine adsorption performance can still be maintained after multiple cycles. In addition, the CMPs demonstrate good adsorption performance in an n-hexane solution of iodine, and the kinetic experimental data follow the pseudo-second-order model. The hierarchical porosity, extended π-conjugated skeleton, and rich electron-donor nitrogen sites of the CMPs could contribute to their excellent iodine adsorption performance. The knowledge information obtained in this work could open up new possibilities for designing novel CMPs targeting a wide range of environment-related applications.

Identification of urinary extracellular vesicles differentially expressed RNAs in diabetic nephropathy via whole-transcriptome integrated analysis.

BACKGROUND: Diabetic nephropathy (DN) is a common systemic microvascular complication of diabetes and a leading cause of chronic kidney disease worldwide. Urinary extracellular vesicles (uEVs), which are natural nanoscale vesicles that protect RNA from degradation, have the potential to serve as an invasive diagnostic biomarker for DN. METHODS: We enrolled 24 participants, including twelve with renal biopsy-proven T2DN and twelve with T2DM, and isolated uEVs using ultracentrifugation. We performed microarrays for mRNAs, lncRNAs, and circRNAs in parallel, and Next-Generation Sequencing for miRNAs. Differentially expressed RNAs (DE-RNAs) were subjected to CIBERSORTx, ssGSEA analysis, GO enrichment, PPI network analysis, and construction of the lncRNA/circRNA-miRNA-mRNA regulatory network. Candidate genes and potential biomarker RNAs were validated using databases and machine learning models. RESULTS: A total of 1684 mRNAs, 126 lncRNAs, 123 circRNAs and 66 miRNAs were found in uEVs in T2DN samples compared with T2DM. CIBERSORTx revealed the involvement of uEVs in immune activity and ssGSEA explored possible cell or tissue sources of uEVs. A ceRNA co-expression and regulation relationship network was constructed. Candidate genes MYO1C and SP100 mRNA were confirmed to be expressed in the kidney using Nephroseq database, scRNA-seq dataset, and Human Protein Atlas database. We further selected 2 circRNAs, 2 miRNAs, and 2 lncRNAs from WGCNAs and ceRNAs and demonstrated their efficacy as potential diagnostic biomarkers for T2DN using machine learning algorithms. CONCLUSIONS: This study reported, for the first time, the whole-transcriptome genetic resources found in urine extracellular vesicles of T2DN patients. The results provide additional support for the possible interactions, and regulators between RNAs from uEVs themselves and as potential biomarkers in DN.

Visible-light-excitable aqueous afterglow exhibiting long emission wavelength and ultralong afterglow lifetime of 7.64 s.

We utilize the dopant-matrix strategy and emulsion polymerization to obtain aqueous afterglow dispersions from a liquid precursor, which avoids the processing of solid materials, protects organic triplets and achieves long phosphorescence lifetime of 7.64 s. The aqueous afterglow dispersions display great potential for biomedical applications due to their ultralong-lived excited states.

Ecosystem carbon storage considering combined environmental and land-use changes in the future and pathways to carbon neutrality in developed regions.

Assessing the carbon storage capacity of terrestrial ecosystems is crucial for land management and carbon reduction policymaking. There is still a knowledge gap regarding how ecosystem carbon storage will be impacted by combined environmental and land-use factors and their spatial-temporal changes, especially in developed regions where urbanization has slowed down. This study investigated how developed regions in subtropical and tropical areas might increase carbon storage and achieve carbon neutrality, using Guangdong Province in South China as an example. Based on the sustainable development assumption, three land-management scenarios were developed and simulated for 2020-2060 using the Patch-generating Land Use Simulation model. Without considering disturbance and natural losses, carbon storage was estimated by net ecosystem productivity (NEP)-the difference between net primary productivity (NPP) and heterotrophic respiration (HR). NPP was predicted using an artificial neural network model trained by historical NPP data and 16 environmental and land-use variables. HR was predicted using soil respiration models from previous research. Based on the balance between carbon storage and emissions, we predicted the allowable fossil fuel consumption to achieve net-zero CO2 emissions in 2060. The results show that Guangdong's total carbon storage changes from 73.7 MtC in 2020 to 70.6-74.8 MtC in 2060 under different scenarios. Nonlinear relationships exist between the carbon stored and the areas of different land-use types. Topography, temperatures, and land-use configurations jointly lead to significantly varied carbon storage between croplands and between forests in space and time. Protecting and regenerating forests in subtropical areas and forest edges is more effective than afforestation in lowland tropical areas for storing carbon. Net-zero CO2 emissions rely more on reducing emissions than land management. To achieve this, the proportion of fossil energy in total energy consumption should be lowered from 75.5 % in 2020 to ~25 % in 2060.

Burden of oral disorders, 1990-2019: estimates from the Global Burden of Disease Study 2019.

Introduction: The aim of this study was to understand the global incidence and disability-adjusted life years (DALY) of oral disorders by age, gender, region, and Sociodemographic Index (SDI) from 1990 to 2019. Material and methods: The estimated annual percentage change (EAPC) and 95% confidence intervals (CIs) were used to assess the trends in age-standardized incidence and DALY rates from 1990 to 2019. Results: The global age-standardized incidence rate (EAPC = 0.01) of oral disorders increased slightly from 1990 to 2019. From 1990 to 2019, the age-standardized DALY rate decreased in high-SDI (EAPC = -0.43) and high-middle-SDI (EAPC = -0.14) regions, but it showed increasing trends in low-SDI (EAPC = 0.22), low-middle-SDI (EAPC = 0.36), and middle-SDI (EAPC = 0.17) regions. The EAPC in the age-standardized DALY rate was negatively correlated with the regional SDI value (ρ = -0.402, p = 0.001). From 1990 to 2019, the region with the largest increase in age-standardized DALY rate was South Asia (EAPC = 0.67), while the country with the greatest increase in age-standardized DALY rate was India (EAPC = 0.82). Conclusions: From 1990 to 2019, the global age-standardized incidence rate of oral disorders showed a slight increasing trend. It is necessary to control the increase in DALY and the disease burden associated with oral disorders in low-, low-middle-, and middle-SDI regions, such as South Asia, particularly in India.

Urate-lowering therapy adherence and the association with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concern in Chinese gout patients: a cross-sectional study.

This study aims to assess urate-lowering therapy adherence and the relationship with medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns in Chinese gout patients during the COVID-19 outbreak. 101 gout patients receiving urate-lowering therapy were involved to evaluate adherence, medication beliefs, self-efficacy, depression, anxiety, and COVID-19 pandemic-related concerns via a mobile app-based questionnaire. Statistical analysis was performed using SPSS 22.0. A total of 101 valid responses were included in the statistical analysis. The results showed that, the rate of adherence to urate-lowering therapy during the COVID-19 outbreak was 22.8% in Chinese patients with gout, higher than that in normal times (9.6%). Compared to the adherent group, non-adherent gout patients had shorter disease duration, lower self-efficacy, lower necessity about urate-lowering therapy score, higher concerns about urate-lowering therapy score, and smaller necessity-concerns differential. Depression and anxiety rates (3.0% and 5.0%, respectively) during the COVID-19 break were lower than that in normal times. Additionally, depression, anxiety, as well as COVID-19 pandemic-related concerns (27.7%) were not related to urate-lowering therapy adherence. In conclusion, adherence rate to urate-lowering therapy in Chinese gout patients during the COVID-19 outbreak was 22.8%, higher than normal times, but still very poor. Except for a little concern about being more susceptible to the virus, patients' mental state is relatively good. While the country puts great efforts into COVID-19 prevention and control, attention must also be paid to the medication management of patients with chronic diseases such as gout.

Corrigendum: Relationship between serum iPTH and peritonitis episodes in patients undergoing continuous ambulatory peritoneal dialysis.

[This corrects the article DOI: 10.3389/fendo.2023.1081543.].

Differences in primary and secondary stroke prevention strategies for Chinese men and women.

This study aimed to explore whether stroke prevention strategies differ for men and women. Data used were from China Kadoorie Biobank. According to the China-PAR Project model, a predicted 10-year stroke risk of ≥7% is defined as a high stroke risk. The effects of risk factor control and medication use as primary and secondary stroke prevention strategies were assessed, respectively. Logistic regression models were used to assess the sex-specific differences in the primary and secondary stroke prevention practices. Of the 512,715 participants (59.0% women), 218,972 (57.4% women) had a high risk of stroke and 8884 (44.7% women) had an established stroke. Of high-risk participants, women were considerably less likely than men to receive antiplatelets (odds ratio [OR], 0.80; [95% confidence interval, CI, 0.72-0.89]), antihypertensives (0.46[0.44-0.48]), and antidiabetics (0.65[0.60-0.70]). Meanwhile, stroke women were significantly less likely to receive antiplatelets (0.75[0.65-0.85]) but more likely to receive antidiabetics (1.56 [1.34-1.82]) than their male counterparts. Besides, differences were found in risk factor control between women and men. Sex-specific differences in stroke prevention strategies are prevalent in China. Effective prevention requires the implementation of better overall nationwide strategies and special emphasis on women.

Three-dimensional covalent organic frameworks with pto and mhq-z topologies based on Tri- and tetratopic linkers.

Three-dimensional (3D) covalent organic frameworks (COFs) possess higher surface areas, more abundant pore channels, and lower density compared to their two-dimensional counterparts which makes the development of 3D COFs interesting from a fundamental and practical point of view. However, the construction of highly crystalline 3D COF remains challenging. At the same time, the choice of topologies in 3D COFs is limited by the crystallization problem, the lack of availability of suitable building blocks with appropriate reactivity and symmetries, and the difficulties in crystalline structure determination. Herein, we report two highly crystalline 3D COFs with pto and mhq-z topologies designed by rationally selecting rectangular-planar and trigonal-planar building blocks with appropriate conformational strains. The pto 3D COFs show a large pore size of 46 Å with an extremely low calculated density. The mhq-z net topology is solely constructed from totally face-enclosed organic polyhedra displaying a precise uniform micropore size of 1.0 nm. The 3D COFs show a high CO2 adsorption capacity at room temperature and can potentially serve as promising carbon capture adsorbents. This work expands the choice of accessible 3D COF topologies, enriching the structural versatility of COFs.

Relationship between serum iPTH and peritonitis episodes in patients undergoing continuous ambulatory peritoneal dialysis.

Background: Peritonitis is considered as one of the most serious complications that cause hospitalization in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). There is limited evidence on the impact of the parathyroid hormone (PTH) on the first peritoneal dialysis (PD)-associated peritonitis episode. We aimed to investigate the influence of serum intact parathyroid hormone (iPTH) on peritonitis in patients undergoing PD. Methods: This was a retrospective cohort study. Patients undergoing initial CAPD from a single center in China were enrolled. The baseline characteristics and clinical information were recorded. The primary outcome of interest was the occurrence of the first PD-associated peritonitis episode. Five Cox proportional hazard models were constructed in each group set. In group set 1, all participants were divided into three subgroups by tertiles of the serum concentration of iPTH; in group set 2, all participants were divided into three subgroups based on the serum concentration of iPTH with 150 pg/ml interval (<150, 150-300, and >300 pg/ml). Hazard ratios and 95% confidence intervals (CIs) were calculated for each model. The multivariate linear regression analysis elimination procedure assessed the association between the clinical characteristics at baseline and the iPTH levels. Restricted cubic spline models were constructed, and stratified analyses were also conducted. Results: A total of 582 patients undergoing initial PD (40% women; mean age, 45.1 ± 11.5 years) from a single center in China were recruited. The median follow-up duration was 25.3 months. Multivariate Cox regression analysis showed that, in the fully adjusted model, a higher serum iPTH level (tertile 3, iPTH >300 pg/ml) was significantly associated with a higher risk of PD-associated peritonitis at 3 years [tertile 3: hazard ratio (HR) = 1.53, 95%CI = 1.03-2.55, p = 0.03; iPTH > 300 pg/ml: HR = 1.57, 95%CI = 1.08-2.27, p = 0.02]. The hazard ratio for every 100 pg/ml increase in serum iPTH level was 1.12 (95%CI = 1.05-1.20, p < 0.01) in the total cohort when treating iPTH as a continuous variable. Conclusions: An elevated iPTH level was significantly associated with an increased risk of peritonitis in patients undergoing CAPD.

Prediction of the Molecular Subtype of IDH Mutation Combined with MGMT Promoter Methylation in Gliomas via Radiomics Based on Preoperative MRI.

BACKGROUND: The molecular subtype of IDH mut combined with MGMT meth in gliomas suggests a good prognosis and potential benefit from TMZ chemotherapy. The aim of this study was to establish a radiomics model to predict this molecular subtype. METHOD: The preoperative MR images and genetic data of 498 patients with gliomas were retrospectively collected from our institution and the TCGA/TCIA dataset. A total of 1702 radiomics features were extracted from the tumour region of interest (ROI) of CE-T1 and T2-FLAIR MR images. Least absolute shrinkage and selection operator (LASSO) and logistic regression were used for feature selection and model building. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive performance of the model. RESULTS: Regarding clinical variables, age and tumour grade were significantly different between the two molecular subtypes in the training, test and independent validation cohorts (p < 0.05). The areas under the curve (AUCs) of the radiomics model based on 16 selected features in the SMOTE training cohort, un-SMOTE training cohort, test set and independent TCGA/TCIA validation cohort were 0.936, 0.932, 0.916 and 0.866, respectively, and the corresponding F1-scores were 0.860, 0.797, 0.880 and 0.802. The AUC of the independent validation cohort increased to 0.930 for the combined model when integrating the clinical risk factors and radiomics signature. CONCLUSIONS: radiomics based on preoperative MRI can effectively predict the molecular subtype of IDH mut combined with MGMT meth.

Integrated analysis of RNA methylation regulators crosstalk and immune infiltration for predictive and personalized therapy of diabetic nephropathy.

BACKGROUND: RNA methylation is a widely known post-transcriptional regulation which exists in many cancer and immune system diseases. However, the potential role and crosstalk of five types RNA methylation regulators in diabetic nephropathy (DN) and immune microenvironment remain unclear. METHODS: The mRNA expression of 37 RNA modification regulators and RNA modification regulators related genes were identified in 112 samples from 5 Gene Expression Omnibus datasets. Nonnegative Matrix Factorization clustering method was performed to determine RNA modification patterns. The ssGSEA algorithms and the expression of human leukocyte antigen were employed to assess the immune microenvironment characteristics. Risk model based on differentially expression genes responsible for the modification regulators was constructed to evaluate its predictive capability in DN patients. Furthermore, the results were validated by using immunofluorescence co-localizations and protein experiments in vitro. RESULTS: We found 24 RNA methylation regulators were significant differently expressed in glomeruli in DN group compared with control group. Four methylation-related genes and six RNA regulators were introduced into riskScore model using univariate Logistic regression and integrated LASSO regression, which could precisely distinguish the DN and healthy individuals. Group with high-risk score was associated with high immune infiltration. Three distinct RNA modification patterns were identified, which has significant differences in immune microenvironment, biological pathway and eGFR. Validation analyses showed the METTL3, ADAR1, DNMT1 were upregulated whereas YTHDC1 was downregulated in DN podocyte cell lines comparing with cells cultured by the normal glucose. CONCLUSION: Our study reveals that RNA methylation regulators and immune infiltration regulation play critical roles in the pathogenesis of DN. The bioinformatic analyses combine with verification in vitro could provide robust evidence for identification of predictive RNA methylation regulators in DN.