The erlin1/erlin2 complex binds to and stabilizes phosphatidylinositol 3-phosphate and regulates autophagy.

The erlin1/erlin2 (E1/E2) complex is an endoplasmic reticulum membrane-located assemblage of the proteins erlin1 and erlin2. Here, we demonstrate direct and selective binding of phosphatidylinositol 3-phosphate (PI(3)P) to recombinant erlins and that disruption or deletion of the E1/E2 complex reduces HeLa cell PI(3)P levels by ∼50 %. This reduction correlated with a decrease in autophagic flux, with no effect on the endocytic pathway, and was not due to reduced VPS34 kinase activity, which is critical for maintaining steady-state PI(3)P levels. Pharmacological inhibition of VPS34 and suppression of PI(3)P levels caused a similar reduction in autophagic flux. Overall, these data indicate that by binding to PI(3)P, the E1/E2 complex plays an important role in maintaining the steady-state levels of PI(3)P and, thus, sustains some key PI(3)P-dependent processes, e.g., autophagy.

BDNF mimetics recover palmitic acid-induced injury in cardiomyocytes by ameliorating Akt-dependent mitochondrial impairments.

Cardiac lipotoxicity is a prevalent consequence of lipid metabolism disorders occurring in cardiomyocytes, which in turn precipitates the onset of heart failure. Mimetics of brain-derived neurotrophic factor (BDNF), such as 7,8-dihydroxyflavone (DHF) and 7,8,3'-trihydroxyflavone (THF), have demonstrated significant cardioprotective effects. However, it remains unclear whether these mimetics can protect cardiomyocytes against lipotoxicity. The aim of this study was to examine the impact of DHF and THF on the lipotoxic effects induced by palmitic acid (PA), as well as the concurrent mitochondrial dysfunction. H9c2 cells were subjected to treatment with PA alone or in conjunction with DHF or THF. Various factors such as cell viability, lactate dehydrogenase (LDH) release, death ratio, and mitochondrial function including mitochondrial membrane potential (MMP), mitochondrial-derived reactive oxygen species (mito-SOX) production, and mitochondrial respiration were assessed. PA dose-dependently reduced cell viability, which was restored by DHF or THF. Additionally, both DHF and THF decreased LDH content, death ratio, and mito-SOX production, while increasing MMP and regulating mitochondrial oxidative phosphorylation in cardiomyocytes. Moreover, DHF and THF specifically activated Akt signaling. The protective effects of DHF and THF were abolished when an Akt inhibitor was used. In conclusion, BDNF mimetics attenuate PA-induced injury in cardiomyocytes by alleviating mitochondrial impairments through the activation of Akt signaling.

Circulating Myokines as Novel Biomarkers for Cardiovascular Diseases.

Myokines are a group of cytokines or polypeptides released from skeletal muscle during exercise. Growing evidence suggests that myokines are associated with the development of cardiovascular disease (CVD). Moreover, several myokines in peripheral blood exhibit dynamic changes in different CVD stages. This review summarizes the potential roles of myokines such as myostatin, irisin, brain-derived neurotrophic factor, mitsugumin 53, meteorin-like, and apelin in various CVD, including myocardial infarction, heart failure, atherosclerosis, hypertension, and diabetes. The association of these myokines with biomarkers currently being used in clinical practice is also discussed. Furthermore, the review considers the emerging role of myokines in CVD and addresses the challenges remaining in translating these discoveries into novel clinical biomarkers for CVD.

Abnormal Degraded Tapetum 1 (ADT1) is required for tapetal cell death and pollen development in rice.

The timely degradation of tapetum, the innermost somatic anther cell layer in flowering plants, is critical for pollen development. Although several genes involved in tapetum development have been characterized, the molecular mechanisms underlying tapetum degeneration remain elusive. Here, we showed that mutation in Abnormal Degraded Tapetum 1 (ADT1) resulted in overaccumulation of Reactive Oxygen Species (ROS) and abnormal anther development, causing earlier tapetum Programmed Cell Death (PCD) and pollen abortion. ADT1 encodes a nuclear membrane localized protein, which is strongly expressed in the developing microspores and tapetal cells during early anther development. Moreover, ADT1 could interact with metallothionein MT2b, which was related to ROS scavenging and cell death regulation. These findings indicate that ADT1 is required for proper timing of tapetum PCD by regulating ROS homeostasis, expanding our understanding of the regulatory network of male reproductive development in rice.

Neurological manifestations and risk factors associated with poor prognosis in hospitalized children with Omicron variant infection.

There are increasing reports of neurological manifestation in children with coronavirus disease 2019 (COVID-19). However, the frequency and clinical outcomes of in hospitalized children infected with the Omicron variant are unknown. The aim of this study was to describe the clinical characteristics, neurological manifestations, and risk factor associated with poor prognosis of hospitalized children suffering from COVID-19 due to the Omicron variant. Participants included children older than 28 days and younger than 18 years. Patients were recruited from December 10, 2022 through January 5, 2023. They were followed up for 30 days. A total of 509 pediatric patients hospitalized with the Omicron variant infection were recruited into the study. Among them, 167 (32.81%) patients had neurological manifestations. The most common manifestations were febrile convulsions (n = 90, 53.89%), viral encephalitis (n = 34, 20.36%), epilepsy (n = 23, 13.77%), hypoxic-ischemic encephalopathy (n = 9, 5.39%), and acute necrotizing encephalopathy (n = 6, 3.59%). At discharge, 92.81% of patients had a good prognosis according to the Glasgow Outcome Scale (scores ≥ 4). However, 7.19% had a poor prognosis. Eight patients died during the follow-up period with a cumulative 30-day mortality rate of 4.8% (95% confidence interval (CI) 1.5-8.1). Multivariate analysis revealed that albumin (odds ratio 0.711, 95% CI 0.556-0.910) and creatine kinase MB (CK-MB) levels (odds ratio 1.033, 95% CI 1.004-1.063) were independent risk factors of poor prognosis due to neurological manifestations. The area under the curve for the prediction of poor prognosis with albumin and CK-MB was 0.915 (95%CI 0.799-1.000), indicating that these factors can accurately predict a poor prognosis.          Conclusion: In this study, 32.8% of hospitalized children suffering from COVID-19 due to the Omicron variant infection experienced neurological manifestations. Baseline albumin and CK-MB levels could accurately predict poor prognosis in this patient population. What is Known: • Neurological injury has been reported in SARS-CoV-2 infection; compared with other strains, the Omicron strain is more likely to cause neurological manifestations in adults. • Neurologic injury in adults such as cerebral hemorrhage and epilepsy has been reported in patients with Omicron variant infection. What is New: • One-third hospitalized children with Omicron infection experience neurological manifestations, including central nervous system manifestations and peripheral nervous system manifestations. • Albumin and CK-MB combined can accurately predict poor prognosis (AUC 0.915), and the 30-day mortality rate of children with Omicron variant infection and neurological manifestations was 4.8%.

Development and validation of a deep learning model for predicting postoperative survival of patients with gastric cancer.

BACKGROUND: Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. METHODS: A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. RESULTS: DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. CONCLUSIONS: DL-based model was established to accurately predict the survival rate of postoperative patients with GC.

A novel standard-free detection of adulteration method for sildenafil derivatives in dietary supplements.

The rapid and accurate detection of illegal adulteration of chemical drugs into dietary supplements is a big challenge in the food chemistry field. Detection of compounds without a standard reference is even more difficult; however, this is a common situation. Here in this study, a novel "standard-free detection of adulteration" (SFDA) method was proposed and phosphodiesterase-5 inhibitor derivatives were used as an example to figure out the possibility and reliability of this SFDA method. After analysis by quadrupole coupled time of flight-tandem mass spectrometry detection and multivariable statistics, six common fragment ions were chosen to indicate whether adulteration was present or not, while 20 characteristic fragment ions indicated whether adulteration was by nitrogen-containing heterocycles or by anilines. Furthermore, the quantitative methods were conducted by high-performance liquid chromatography-tandem mass spectrometry. In a word, this strategy allows for a quick determination of dietary supplement adulteration without any need for standard materials, improving the efficacy of food safety testing.

Liquiritin targeting Th17 cells differentiation and abnormal proliferation of keratinocytes alleviates psoriasis via NF-κB and AP-1 pathway.

Psoriasis is a common immune-mediated inflammatory skin disease, caused by disturbed interactions between keratinocytes and immune cells. Chinese medicine shows potential clinical application for its treatment. Liquiritin is a flavone compound extracted from licorice and shows potential antitussive, antioxidant and antiinflammatory effects, and therefore may have potential as a psoriasis therapeutic. The aim of this work was to examine the possible roles that liquiritin may have in treating psoriasis. HaCaT cells were stimulated by TNF-α with or without liquiritin, harvested for analysis by western blots and RT-qPCR, and the cellular supernatants were collected and analyzed by ELISA for cytokines. In addition, 4 groups of mice were examined: Normal, Vehicle, LQ-L and LQ-H. The mice were sacrificed after 6 days and analyzed using IHC, ELISA, RT-qPCR and flow cytometry. The results showed that liquiritin could significantly inhibit the progression of psoriasis both in vitro and in vivo. Liquiritin strongly suppressed the proliferation of HaCaT keratinocytes but did not affect cell viability. Moreover, liquiritin alleviated imiquimod-induced psoriasis-like skin inflammation and accumulation of Th17 cells and DCs in vivo. In TNF-α-induced HaCaT keratinocytes, both protein and mRNA expression levels of inflammatory cytokines were sharply decreased. In imiquimod-induced mice, the activation of NF-κB and AP-1 was reduced after treatment with liquiritin. Collectively, our results show that liquiritin might act as a pivotal regulator of psoriasis via modulating NF-κB and AP-1 signal pathways.

Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma.

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.

Haplotype-resolved genome of a heterozygous wild peach reveals the PdaWRKY4-PdaCYP716A1 module mediates resistance to aphids by regulating betulin biosynthesis.

Wild species of domesticated crops provide valuable genetic resources for resistance breeding. Prunus davidiana, a wild relative of peach with high heterozygosity and diverse stress tolerance, exhibits high resistance against aphids. However, the highly heterozygous genome of P. davidiana makes determining the underlying factors influencing resistance traits challenging. Here, we present the 501.7 Mb haplotype-resolved genome assembly of P. davidiana. Genomic comparisons of the two haplotypes revealed 18,152 structural variations, 2,699 Pda_hap1-specific and 2,702 Pda_hap2-specific genes, and 1,118 allele-specific expressed genes. Genome composition indicated 4.1% of the P. davidiana genome was non-peach origin, out of which 94.5% was derived from almond. Based on the haplotype genome, the aphid resistance quantitative trait locus (QTL) was mapped at the end of Pda03. From the aphid resistance QTL, PdaWRKY4 was identified as the major dominant gene, with a 9-bp deletion in its promoter of the resistant phenotype. Specifically, PdaWRKY4 regulates aphid resistance by promoting PdaCYP716A1-mediated anti-aphid metabolite betulin biosynthesis. Moreover, we employed a genome design to develop a breeding workflow for rapidly and precisely producing aphid-resistant peaches. In conclusion, this study identifies a novel aphid resistance gene and provides insights into genome design for the development of resistant fruit cultivars.

[Role of macrophage polarization in hypertension and traditional Chinese medicine intervention: a review].

Hypertension is known to be a chronic inflammatory state and a key risk factor for heart failure, coronary heart disease, and atherosclerosis. Macrophages in the circulatory system are the main cell group that constitutes the immune system and participates in the inflammatory response. Depending on the local microenvironment, macrophages can be polarized into pro-inflammatory(M1) and anti-inflammatory(M2) phenotypes. When blood pressure is elevated, M1 macrophages can release pro-inflammatory cytokines and chemokines to generate an immune response. However, an excessive immune response can lead to tissue damage, and M2 macrophages release anti-inflammatory cytokines to promote the repair of wounds and tissue damage. It is clear that the dynamic balance between M1 and M2 macrophages resembles the traditional Chinese medicine(TCM) theory of Yin and Yang. That is, when Yin and Yang are imbalanced, the human body will exhibit pathological states, e.g., altered blood pressure rhythms. Studies have confirmed that TCM can produce positive therapeutic effects on hypertension by regulating macrophage polarization. Therefore, this study reviews the studies about the TCM regulation of macrophage polarization and summarized the mechanisms of TCM intervention in hypertension, with the aim of providing evidence for clinical treatment and ideas for scientific research design.

Engineering Telodendrimer Nanocarriers for Monomeric Amphotericin B Delivery.

Systemic fungal infections are an increasingly prevalent health problem. Amphotericin B (AmB), a hydrophobic polyene antibiotic, remains the drug of choice for life-threatening invasive fungal infections. However, it has dose-limiting side effects, including nephrotoxicity. The efficacy and toxicity of AmB are directly related to its aggregation state. Here, we report the preparation of a series of telodendrimer (TD) nanocarriers with the freely engineered core structures for AmB encapsulation to fine-tune AmB aggregation status. The reduced aggregation status correlates well with the optimized antifungal activity, attenuated hemolytic properties, and reduced cytotoxicity to mammalian cells. The optimized TD nanocarrier for monomeric AmB encapsulation significantly increases the therapeutic index, reduces the in vivo toxicity, and enhances antifungal effects in mouse models with Candida albicans infection in comparison to two common clinical formulations, i.e., Fungizone and AmBisome.

The effect of long-term care insurance on healthcare utilization of middle-aged and older adults: evidence from China health and retirement longitudinal study.

BACKGROUND: As global ageing continues to increase and many countries face challenges from the growing demand for long-term care. Drawing on the experiences of developed countries, developing countries have explored their own suitable long-term care insurance and have shown strong potential for development and research prospects. However, due to their late start, relevant research is underrepresented in the global research network and still needs to be supplemented. The present study hopes to examine the effect of long-term care insurance on healthcare utilization among the middle-aged and elderly from an empirical perspective, using China as an example. METHODS: Panel data from wave 3 (2015) and wave 4 (2018) of the nationally-representative China health and retirement longitudinal study were selected to obtain a sample of 661 processing participants and 16,065 control participants after matching the policy implementation time in the first pilot cities, and quantitative analysis was conducted using difference-in-differences propensity score matching estimator method to assess the net effect of long-term care insurance on health care utilization among the middle-aged and elderly adults. RESULTS: In the matched frequency-weighted regression difference-in-differences estimator results, long-term care insurance had a negative effect on the number and costs of annual hospitalizations at the 5% significance level (key variable values of - 0.0568101 and - 1236.309, respectively) and a non-significant effect on outpatient service utilization (P > 0.05). Further exploration of the heterogeneous effect of it revealed that implementation had a more significant negative effect on hospitalization utilization for middle-aged and older people in the East and for those with higher levels of education or attended care. CONCLUSION: Long-term care insurance has played a role in controlling hospitalization costs but has not yet achieved the expected effect in controlling outpatient costs. The policy effects in terms of regional distribution and education level and care situation have been variable. The treatment plan of long-term care insurance needs to be improved, the supply of resources for long-term care services should be increased, and the promotion of long-term care insurance and health science should be given attention.

Engineering Nanotrap Hydrogel for Immune Modulation in Wound Healing.

Imbalanced immune regulation leads to the abnormal wound healing process, e.g., chronic unhealing wound or hypertrophic scar formation. Thus, the attenuation of the overflowing inflammatory factors is a viable approach to maintain the homeostatic immune regulation to facilitate normal wound healing. A versatile telodendrimer (TD) nanotrap (NT) platform is developed for efficient biomolecular protein binding. The conjugation of TD NT in size-exclusive biocompatible hydrogel resin allows for topical application for cytokine scavenging. Fine-tuning the TD NT density/valency in hydrogel resin controls resin swelling, optimizes molecular diffusion, and improves cytokine capture for effective immune modulation. The hydrogel with reduced TD NT density allows for higher protein/cytokine adsorption capacity with faster kinetics, due to the reduced barrier of TD NT nano-assembly. The positively charged TD NT hydrogel exhibits superior removal of negatively charged proinflammatory cytokines from the lipopolysaccharide (LPS, a potent endotoxin) primed immune cell culture medium. The negatively charged TD NT hydrogel removes positively charged anti-inflammatory cytokines efficiently from cell culture medium. TD NT hydrogel effectively constrains the local inflammation induced by subcutaneous LPS injection in mice. These results indicate the great potential applications of the engineered TD NT hydrogel as topical immune modulatory treatments to attenuate local inflammation.

Efficient genome editing in cotton using the virus-mediated CRISPR/Cas9 and grafting system.

KEY MESSAGE: The extensive application of CRISPR in cotton was limited due to the labor-intensive transformation process. Thus, we here established a convenient method of CRISPR in cotton by CLCrV-mediated sgRNA delivery.

A potential paradigm in CRISPR/Cas systems delivery: at the crossroad of microalgal gene editing and algal-mediated nanoparticles.

Microalgae as the photosynthetic organisms offer enormous promise in a variety of industries, such as the generation of high-value byproducts, biofuels, pharmaceuticals, environmental remediation, and others. With the rapid advancement of gene editing technology, CRISPR/Cas system has evolved into an effective tool that revolutionised the genetic engineering of microalgae due to its robustness, high target specificity, and programmability. However, due to the lack of robust delivery system, the efficacy of gene editing is significantly impaired, limiting its application in microalgae. Nanomaterials have become a potential delivery platform for CRISPR/Cas systems due to their advantages of precise targeting, high stability, safety, and improved immune system. Notably, algal-mediated nanoparticles (AMNPs), especially the microalgae-derived nanoparticles, are appealing as a sustainable delivery platform because of their biocompatibility and low toxicity in a homologous relationship. In addition, living microalgae demonstrated effective and regulated distribution into specified areas as the biohybrid microrobots. This review extensively summarised the uses of CRISPR/Cas systems in microalgae and the recent developments of nanoparticle-based CRISPR/Cas delivery systems. A systematic description of the properties and uses of AMNPs, microalgae-derived nanoparticles, and microalgae microrobots has also been discussed. Finally, this review highlights the challenges and future research directions for the development of gene-edited microalgae.

LncRNA XR_595552 inhibition alleviates intermittent hypoxia-induced cardiomyocyte damage via activating the PI3K/AKT pathway.

BACKGROUND: Although the long noncoding RNAs (lncRNAs) expression profiles have been observed in previous study, the biological functions and underlying mechanisms of lncRNAs in OSA-related cardiac injury have not been elucidated. In the present study, we investigated a novel lncRNA, lncRNA XR_595552, and evaluated its role in intermittent hypoxia (IH)-induced damage in H9c2 cardiomyocytes. METHODS: H9c2 cells were exposed to IH condition. Real-time quantitative polymerase chain reaction (RT-qPCR) was conducted to measure the expression changes of lncRNA XR_595552 in H9c2 cells stimulated by IH. H9c2 cells were subjected to IH after transfection. CCK-8 was used to evaluate cell viability, and apoptosis was analyzed by Western blotting. Additionally, the regulatory relationship between lncRNA XR_595552 and PI3K/AKT was tested by RT-qPCR and Western blot. RESULTS: IH significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis). lncRNA XR_595552 was upregulated in a cell model of IH. Inhibition of lncRNA XR_595552 protected H9c2 cells against IH-induced damage, as the viability was increased, Bax, Caspase-9, and Caspase-3 were downregulated, and Bcl-2 was upregulated. More interestingly, lncRNA XR_595552 downregulation activated the PI3K/AKT pathway. Blocking the PI3K/AKT signal pathway by the use of LY294002 eliminated the myocardioprotective effects of lncRNA XR_595552 in H9c2 cells under IH condition. CONCLUSIONS: The results show that lncRNA XR_595552, a novel lncRNA, may play a protective role in attenuating IH-induced injury in cardiomyocytes via a regulating PI3K/AKT pathway. The findings suggest that this lncRNA could serve as a therapeutic target to treat OSA-related cardiovascular disorders.

Transcriptomic and metabolomic insights into the defense response to HFRs in Arabidopsis.

Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.

A preliminary nomogram model for predicting relapse of patients with primary membranous nephropathy.

OBJECTIVE: To explore the predictive factors and establish a nomogram model for predicting relapse risk in primary membranous nephropathy (PMN). METHODS: The clinical, laboratory, pathological and follow-up data of patients with biopsy-proven membranous nephropathy were collected in the Affiliated Hospital of Qingdao University. A total of 400 PMN patients who achieved remission were assigned to the development group (n = 280) and validation group (n = 120) randomly. Cox regression analysis was performed in the development cohort to determine the predictive factors of relapse in PMN patients, a nomogram model was established based on the multivariate Cox regression analysis and validated in the validation group. C-index and calibration plots were used to evaluate the discrimination and calibration performance of the model respectively. RESULT: Hyperuricemia (HR = 2.938, 95% CI 1.875-4.605, p < 0.001), high C-reactive protein (CRP) (HR = 1.147, 95% CI 1.086-1.211, p < 0.001), and treatment with calcineurin inhibitors with or without glucocorticoids (HR = 2.845, 95%CI 1.361-5.946, p = 0.005) were independent risk factors, while complete remission (HR = 0.420, 95%CI 0.270-0.655, p < 0.001) was a protective factor for relapse of PMN according to multivariate Cox regression analysis, then a nomogram model for predicting relapse of PMN was established combining the above indicators. The C-indices of this model were 0.777 (95%CI 0.729-0.825) and 0.778 (95%CI 0.704-0.853) in the development group and validation group respectively. The calibration plots showed that the predicted relapse probabilities of the model were consistent with the actual probabilities at 1, 2 and 3 years, which indicated favorable performance of this model in predicting the relapse probability of PMN. CONCLUSIONS: Hyperuricemia, remission status, CRP and therapeutic regimen were predictive factors for relapse of PMN. A novel nomogram model with good discrimination and calibration was constructed to predict relapse risk in patients with PMN early.

Benzoylaconitine Alleviates Progression of Psoriasis via Suppressing STAT3 Phosphorylation in Keratinocytes.

Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.