Lifestyle improvement and the reduced risk of cardiovascular disease: the China-PAR project.

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS: Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Direct observation of topological magnon polarons in a multiferroic material.

Magnon polarons are novel elementary excitations possessing hybrid magnonic and phononic signatures, and are responsible for many exotic spintronic and magnonic phenomena. Despite long-term sustained experimental efforts in chasing for magnon polarons, direct spectroscopic evidence of their existence is hardly observed. Here, we report the direct observation of magnon polarons using neutron spectroscopy on a multiferroic Fe2Mo3O8 possessing strong magnon-phonon coupling. Specifically, below the magnetic ordering temperature, a gap opens at the nominal intersection of the original magnon and phonon bands, leading to two separated magnon-polaron bands. Each of the bands undergoes mixing, interconverting and reversing between its magnonic and phononic components. We attribute the formation of magnon polarons to the strong magnon-phonon coupling induced by Dzyaloshinskii-Moriya interaction. Intriguingly, we find that the band-inverted magnon polarons are topologically nontrivial. These results uncover exotic elementary excitations arising from the magnon-phonon coupling, and offer a new route to topological states by considering hybridizations between different types of fundamental excitations.

The complete plastid genome sequence of Lysidice brevicalyx (Fabaceae: Detarioideae), an arbor species endemic to China.

The plastid genome of Lysidice brevicalyx was successfully assembled using Illumina sequencing reads for the first time. The complete plastid genome of L. brevicalyx is a circular structure of 159,084 bp with a GC content of 36.4%. It comprises a large single-copy (LSC) region of 87,783 bp, a small single-copy (SSC) region of 19,557 bp, and two inverted repeat regions (IRA and IRB) of 25,872 bp, each. The plastome of L. brevicalyx contains a total of 128 genes, including 83 protein-coding genes, 37 tRNAs, and 8 rRNAs. The phylogenetic analysis strongly supports the monophyly of Lysidice. This study provides the first complete plastid genome sequence of L. brevicalyx and contributes to our understanding of the molecular characteristics and evolutionary relationships of this plant species.

Evolution Law of Structural Form and Heat Transfer Performance of Thermal Insulation System.

Building thermal insulation and energy conservation have become urgent problems in the field of civil engineering because they are important for achieving the goal of carbon neutralization. Thermal conductivity is an important index for evaluating the thermal insulation of materials. To study the influence of different porosity levels on the thermal conductivity of materials, this paper established a random distribution model using MATLAB and conducted a comparative analysis using COMSOL finite element software and classical theoretical numerical calculation formulas. The thermal conductivity of composite materials was determined based on a theoretical calculation formula and COMSOL software simulations, and the theoretical calculation results and simulation results were compared with the measured thermal conductivity of the composites. Furthermore, the influence of the width of the gaps between the materials on the heat transfer process was simulated in the fabricated roof structure. The results showed the following: (1) The thermal conductivity values calculated using the Zimmerman model were quite different from those calculated using the Campbell-Allen model and those calculated using the COMSOL software; (2) The thermal conductivity values calculated using the theoretical calculation formula were lower than the measured data, and the maximum relative error was more than 29%. The COMSOL simulation results were in good agreement with the measured data, and the relative error was less than 5%; (3) When the gap width was less than 60 mm, it increased linearly with the heat transfer coefficient. The heat transfer coefficient increased slowly when the gap width was greater than 60 mm. This was mainly due to the thermal bridge effect inside the insulation system. Based on these research results, a thermal insulation system was prepared in a factory.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention.

OBJECTIVE: To investigate the optimal duration of dual antiplatelet therapy (DAPT) in patients with diabetes mellitus (DM) requiring complex percutaneous coronary intervention (PCI). METHODS: A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group (11-13 months, n = 689) and two prolonged groups (13-24 months, n = 1133; > 24 months, n = 581). RESULTS: Baseline characteristics, angiographic findings, and complexity of PCI were comparable regardless of DAPT duration. The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or > 24 months (4.6% vs. 8.1% vs. 6.0%, P = 0.008), as was the incidence of all-cause death (1.9% vs. 4.6% vs. 2.2%, P = 0.002) and cardiac death (1.0% vs. 3.0% vs. 1.2%, P = 0.002). After adjustment for confounders, DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event [hazard ratio (HR) = 0.544, 95% CI: 0.373-0.795] and all-cause death (HR = 0.605, 95% CI: 0.387-0.944). DAPT for > 24 months was associated with a lower risk of all-cause death (HR = 0.681, 95% CI: 0.493-0.942) and cardiac death (HR = 0.620, 95% CI: 0.403-0.952). The risk of major bleeding was not increased by prolonging DAPT to 13-24 months (HR = 1.356, 95% CI: 0.766-2.401) or > 24 months (HR = 0.967, 95% CI: 0.682-1.371). CONCLUSIONS: For patients with DM undergoing complex PCI, prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Identification and validation of a novel prognostic model for gastric cancer based on m7G-related genes.

Background: The role of N7-methyladenosine (m7G)-related genes in the progression and prognosis of gastric cancer (GC) remains unclear. This study aimed to explore prognostic biomarkers for GC based on m7G methylation regulators and to construct a prognostic risk model. Methods: RNA sequencing profiles with corresponding clinicopathological information associated with GC of which the histological type was stomach adenocarcinoma (STAD) were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. A total of 29 m7G regulators were extracted from previous studies. According to the expression similarity of m7G regulators, the GC samples obtained from TCGA were further classified into 2 clusters demonstrating different overall survival (OS) rates and genetic heterogeneity, and the differentially expressed genes (DEGs) between these 2 clusters were defined as m7G-related genes. Univariate regression analysis and regression analysis were then used to obtain the prognostic m7G-related genes. The samples in TCGA and Genotype-Tissue Expression (GTEx) were used to verify the differential expression and prognostic value of these m7G-related genes contained in the prognostic model. Subsequently, the risk score was combined with other prognostic factors to develop a nomogram. The predictive ability of the nomogram was evaluated by the standard receiver operating characteristic (ROC) curve. Gene set enrichment analysis (GSEA) was used to identify activation pathways in both groups. Finally, the association between the prognostic model and the immune characteristics of GC were appraised. Results: A prognostic model consisting of 11 m7G-related genes was constructed. GC patients in the high-risk group were shown to have a poor prognosis and this result was further demonstrated in each group. The risk model can be applied for patients with different clinical features. The results of GSEA showed that cell adhesion, cell junction, and focal adhesion were highly enriched in the high-risk group. In addition, we found that the expression of programmed cell death ligand 1 (PD-L1) was significantly elevated in the low-risk group, whereas programmed cell death ligand 2 (PD-L2) and tumor necrosis factor receptor superfamily member 4 (TNFRSF4) were overexpressed in the high-risk group. Conclusions: We successfully built and verified a m7G relevant prognostic model for predicting prognosis and providing a new train of thought for improving the treatment of GC.

Cuproptosis-Related 4-Gene Risk Model for Predicting Immunotherapy Drug Response and Prognosis of Kidney Renal Clear Cell Carcinoma.

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.

Manipulating Hubbard-type Coulomb blockade effect of metallic wires embedded in an insulator.

Correlated states have emerged in low-dimensional systems owing to enhanced Coulomb interactions. Elucidating these states requires atomic-scale characterization and delicate control capabilities. Herein, spectroscopic imaging-scanning tunneling microscopy was employed to investigate the correlated states residing in 1D electrons of the monolayer and bilayer MoSe2 mirror twin boundary (MTB). The Coulomb energies, determined by the wire length, drive the MTB into two types of ground states with distinct respective out-of-phase and in-phase charge orders. The two ground states can be reversibly converted through a metastable zero-energy state with in situ voltage pulses, which tune the electron filling of the MTB via a polaronic process, substantiated by first-principles calculations. Our Hubbard model calculation with an exact diagonalization method reveals the ground states as correlated insulators from an on-site U-originated Coulomb interaction, dubbed the Hubbard-type Coulomb blockade effect. Our study lays a foundation for understanding and tailoring correlated physics in complex systems.

Inducing itinerant ferromagnetism by manipulating van Hove singularity in epitaxial monolayer 1T-VSe2.

The itinerant ferromagnetism can be induced by a van Hove singularity (VHS) with a divergent density of states at Fermi level. Utilizing the giant magnified dielectric constant εr of SrTiO3(111) substrate with cooling, here we successfully manipulated the VHS in the epitaxial monolayer (ML) 1T-VSe2 film approaching to Fermi level via the large interfacial charge transfer, and thus induced a two-dimensional (2D) itinerant ferromagnetic state below 3.3 K. Combining the direct characterization of the VHS structure via angle-resolved photoemission spectroscopy (ARPES), together with the theoretical analysis, we ascribe the manipulation of VHS to the physical origin of the itinerant ferromagnetic state in ML 1T-VSe2. Therefore, we further demonstrated that the ferromagnetic state in the 2D system can be controlled through manipulating the VHS by engineering the film thickness or replacing the substrate. Our findings clearly evidence that the VHS can serve as an effective manipulating degree of freedom for the itinerant ferromagnetic state, expanding the application potentials of 2D magnets for the next-generation information technology.

Saponin extract from Achyranthes bidentata Blume alleviates disuse-induced muscle atrophy through PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots of Achyranthes bidentata Blume are one of the regularly used herbal drugs in Chinese medicine, and has been applied for strengthening the muscle and bone for a long time. However, its effect on muscle remains unclear. AIM OF THE STUDY: This paper aims to explore the anti-muscle atrophy effect of A. bidentata, and to clarify the possible signaling pathways involved. MATERIALS AND METHODS: The saponin extract of the roots of A. bidentata (ABSE) was prepared and analyzed, and its activity on myoblast differentiation was assayed with C2C12 cell culture. ABSE was then orally administered at dosage of 35, 70 and 140 mg/kg/day to disuse-induced muscle atrophy mice. The studies on mice body weight and muscle quality were conducted, and Western blot was used for exploring the possible signaling pathways involved in the muscle protective action aided with transcriptome analysis. RESULTS: The total saponin content of ABSE was 59.1%. ABSE promoted the C2C12 cells differentiation to myotube in C2C12 differentiation assay. Further study with disuse-induced muscle atrophy mice model demonstrated that ABSE significantly increased muscle fiber diameter as well as the proportion of slow muscle fibers. Possible mechanism study aided with transcriptome analysis revealed that ABSE alleviated muscle atrophy at least through activation of PI3K/Akt pathway in vivo & vitro. CONCLUSIONS: The saponin extract of the root of A. bidentata (ABSE) has a protective effect on muscle atrophy, and showed a considerable potential in prevention and treatment of muscle atrophy.

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome: five-year results from a large cohort study.

BACKGROUND: To investigate the most appropriate dual antiplatelet therapy (DAPT) duration for patients with acute coronary syndrome (ACS) after drug-eluting stent (DES) implantation in the largest cardiovascular center of China. METHODS: We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013. Patients were divided into four groups based on DAPT duration: standard DAPT group (11-13 months, n=1,568) and prolonged DAPT groups (13-18 months [n=308], 18-24 months [n=2,125], and >24 months [n=1,186]). Baseline characteristics and 5-year clinical outcomes were recorded. RESULTS: Baseline characteristics were similar across the four groups. Among the four groups, those with prolonged DAPT (18-24 months) had the lowest incidence of major adverse cardiovascular and cerebrovascular events (MACCEs) (14.1% vs. 11.7% vs. 9.6% vs. 24.2%, P<0.001), all-cause death (4.8% vs. 3.9% vs. 2.1% vs. 2.6%, P<0.001), cardiac death (3.1% vs. 2.6% vs. 1.4% vs. 1.9%, P=0.004), and myocardial infarction (MI) (3.8% vs. 4.2% vs. 2.5% vs. 5.8%, P<0.001). The incidence of bleeding was not different among the four groups (9.9% vs. 9.4% vs. 11.0% vs. 9.4%, P=0.449). Cox multivariable analysis showed that prolonged DAPT (18-24 months) was an independent protective factor for MACCEs (hazard ratio [HR] 0.802, 95% confidence interval [CI] 0.729-0.882, P<0.001), all-cause death (HR 0.660, 95% CI 0.547-0.795, P<0.001), cardiac death (HR 0.663, 95% CI 0.526-0.835, P<0.001), MI (HR 0.796, 95% CI 0.662-0.957, P=0.015), and target vessel revascularization (HR 0.867, 95% CI 0.755-0.996, P=0.044). Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs. CONCLUSION: For patients with ACS after DES, appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Association between Fruit and Vegetable Intake and Arterial Stiffness: The China-PAR Project.

Objective: This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness. Methods: We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges. Results: Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83). Conclusion: Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.

Superconductivity and density-wave fluctuations in an extended triangular Hubbard model: an application to SnSe2.

We employ the fluctuation-exchange approximation to study the relation of superconducting pairing symmetries and density-wave fluctuations based on the extended triangular Hubbard model upon electron doping and interactions, with an possible application to the layered metal dichalcogenide SnSe2. For the case where the interactions between electrons contain only the on-site Hubbard term, the superconducting pairings are mainly mediated by spin fluctuations, and the spin-singlet pairing with thed-wave symmetry robustly dominates in the low and moderate doping levels, and ad-wave to extendeds-wave transition is observed as the electron doping reachesn = 1. When the near-neighbor site Coulomb interactions are also included, the charge fluctuations are enhanced, and the spin-triplet pairings with thep-wave andf-wave symmetries can be realized in the high and low doping levels, respectively.

Annonaceous Acetogenin Mimic AA005 Inhibits the Growth of TNBC MDA-MB-468 Cells by Altering Cell Energy Metabolism.

Triple-negative breast cancer (TNBC) is a serious health issue for women worldwide and there is still no suitable treatment option. AA005, a structurally simplified mimic of natural Annonaceous acetogenins, presents outstanding properties with impressive cytotoxicity and cell-type selective actions. The present study was aimed at evaluating the potential of AA005 as a therapeutic agent for TNBC. AA005 potently inhibited the growth of TNBC cells at 50 nM level. Inspired by the finding of the phosphatase and tensin homologue (PTEN) tumor suppressor, the effect of AA005 on aerobic glycolysis was investigated in TNBC MDA-MB-468 cells. A short-term AA005 exposure markedly suppressed mitochondrial function in MDA-MB-468 cells, thus activating the aerobic glycolysis to lessen the risk of decreased ATP generation in mitochondria. Prolonging the incubation time of AA005 clearly weakened the aerobic glycolysis in the cells. This was in part attributed to the PI3K-AKT pathway inactivation and subsequent declined glucose uptake. As a consequence, the energy supply was completely cut from the two major energy-producing pathways. Further experiments showed that AA005 resulted in irreversible damage on cell activity including cell cycle and growth, inducing mitochondrial oxidative stress and ultimately leading to cell death. In addition, the in vivo therapeutic efficacy of AA005 was proved on 4T1 xenograft tumor mice model. Our data demonstrate that AA005 exhibited a great potential for future clinical applications in TNBC therapy.

[Recurrent and Refractory Langerhans Cell Histiocytosis in Children Treated with the Combination of Cladribine and Cytarabine].

OBJECTIVE: To observe the efficacy and prognosis of cladribine (2-CdA) combined with cytarabine (Ara-C) regimen in the treatment of relapsed refractory Langerhans cell histiocytosis (LCH) in children. METHODS: Nine patients with relapsed refractory LCH treated with the 2-CdA combined with Ara-C regimen in the Department of Hematology and Oncology of Wuhan Children's Hospital from July 2014 to February 2020 were retrospectively analyzed, and the efficacy and disease status were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines (2009) and the Disease Activity Score (DAS), the drug toxicity were evaluated according to the World Health Organization（WHO） grading criteria for chemotherapy. All patients were followed up for survival status and disease-related sequelae. RESULTS: Before the treatment combining 2-CdA and Ara-C, 7 of 9 patients were evaluated as active disease worse (ADW), and 2 as active disease stable (ADS) with a median disease activity score of 8 (4-15). Of 9 patients, 6 cases achieved non active disease (NAD) and 3 achieved active disease better (ADB) with a median disease activity score of 0 (0 to 5) after 2-6 courses of therapy. All 9 patients experienced WHO grade IV hematologic toxicity and 3 patients had hepatobiliary adverse effects (WHO grade I～II) after treatment. The median follow-up time was 31(1 to 50) months with all 9 patients survived, 3 of the 9 patients experienced sequelae to the disease with 2 combined liver cirrhosis as well as cholestatic hepatitis and 1 with oral desmopressin acetate tablets for diabetes insipidus. CONCLUSION: 2-CdA combined with Ara-C is an effective regimen for the treatment of recurrent refractory LCH in children, and the main adverse effect is hematologic toxicity, which is mostly tolerated in children. Early treatment with this regimen may be considered for patients with multisystem LCH with risky organ involvement who have failed first-line therapy and for patients with relapse.

Metabolomics study of blood pressure salt-sensitivity and hypertension.

BACKGROUND AND AIMS: Identify novel metabolite associations with blood pressure (BP) salt-sensitivity and hypertension. METHODS AND RESULTS: The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Replication study includes 698 Chinese participants who underwent a 3-day baseline examination followed by a 7-day low-sodium feeding and 7-day high-sodium feeding. Latent mixture models identified three trajectories of blood pressure (BP) responses to the sodium interventions. We selected 50 most highly salt-sensitive and 50 most salt-resistant participants for untargeted metabolomics profiling. Multivariable adjusted mixed logistic regression models tested the associations of baseline metabolites with BP salt-sensitivity. Multivariable adjusted mixed linear regression models tested the associations of BP salt-sensitivity with metabolite changes during the sodium interventions. Identified metabolites were tested for associations with hypertension among 1249 Bogalusa Heart Study (BHS) participants using multiple logistic regression. Fifteen salt-sensitivity metabolites were associated with hypertension in the BHS. Baseline values of serine, 2-methylbutyrylcarnitine and isoleucine directly associated with high salt-sensitivity. Among them, serine indirectly associated with hypertension while 2-methylbutyrylcarnitine and isoleucine directly associated with hypertension. Baseline salt-sensitivity status predicted changes in 14 metabolites when switching to low-sodium or high-sodium interventions. Among them, glutamate, 1-carboxyethylvaline, 2-methylbutyrylcarnitine, 3-methoxytyramine sulfate, glucose, alpha-ketoglutarate, hexanoylcarnitine, gamma-glutamylisoleucine, gamma-glutamylleucine, and gamma-glutamylphenylalanine directly associated with hypertension. Conversely, serine, histidine, threonate and 5-methyluridine indirectly associated with hypertension. Together, these metabolites explained an additional 7% of hypertension susceptibility when added to a model including traditional risk factors. CONCLUSIONS: Our findings contribute to the molecular characterization of BP response to sodium and provide novel biological insights into salt-sensitive hypertension.

[Clinical Analysis of Pediatric Acute Myeloid Leukemia with CCLG-AML 2015 Regimen].

OBJECTIVE: To analyze the clinical effects of CCLG-AML-2015 protocol on newly diagnosed children with acute myeloid leukemia (AML). METHODS: The clinical data of 60 newly diagnosed AML children in the Department of Hematology and Oncology, Wuhan Children's Hospital from August 2015 to September 2019 were summarized, the effect of chemotherapy using the CCLG-AML-2015 regimen (hereinafter referred to as the 2015 regimen) were retrospectively analyzed. 42 children with AML treated by the AML-2006 regimen (hereinafter referred to as the 2006 regimen) from February 2010 to July 2015 were used as control group. RESULTS: There were no statistical differences between the 2015 regimen group and the 2006 regimen group in sex, age at first diagnosis, and risk stratification (P>0.05). The complete remission rate of bone marrow cytology after induction of 1 course of chemotherapy (84.7% vs 73.1%, P=0.155), and minimal residual disease detection (MRD) negative (42.3% vs 41.4%, P=0.928) in the 2015 regimen group were not statistically different than those in the 2006 regimen group. The bone marrow cytology CR (98.1% vs 80.6%, P=0.004) and MRD negative (83.3% vs 52.8%, P=0.002) in the 2015 regimen group after 2 courses of induction were higher than those in the 2006 regimen group. The 5-year overall survival (OS) rate in the 2015 regimen group (62.3%±6.4% vs 20.6%±6.4%, P=0.001), the 5-year disease-free survival (EFS) rate (61.0%±6.4% vs 21.0% ±6.4% , P=0.001) were better than those in the 2006 regimen group. The 5-year OS and EFS of high-risk transplant patients in the 2015 regimen group were significantly better than those of high-risk non-transplant patients (OS: 86.6%±9.0% vs 26.7%±11.4%, P=0.000; EFS: 86.6%±9% vs 26.7%±11.4%, P=0.000). CONCLUSION: The 2015 regimen can increase the CR rate after 2 courses of induction compared with the 2006 regimen. High-risk children receiving hematopoietic stem cell transplantation can significantly improve the prognosis.

HA-20 prevents hepatocyte steatosis in metabolic-associated fatty liver disease via regulating Ca2+ relative signalling pathways.

Metabolic-associated fatty liver disease (MAFLD) is caused by hepatocyte steatosis and is associated with obesity, type II diabetes, and heart disease. There are currently no effective drugs to treat MAFLD. This study explored the effect of HA-20, an oleanolic acid derivative, on hepatocyte steatosis in MAFLD. HepG2, L02, and AML12 cells were developed using oleic acid for in vitro MAFLD cell assays, and a high-fat diet + high-fructose diet-induced (HFHF) MAFLD mouse model was established for in vivo studies. The results demonstrated that HA-20 prevented hepatocyte steatosis in cell assays and caused 26.3, 57.7 and 70.0% inhibition of triglyceride (TG) levels in the 5.0, 10.0 and 20.0 µM HA-20 groups, respectively. The EC50 values of HA-20 treatment in HepG2, L02 and AML12 cells were 9.7 ± 0.6 µM, 42.4 ± 3.5 µM and 71.0 ± 14.7 µM, respectively. HA-20 also prevented hepatocyte steatosis in the MAFLD mouse model, the liver triglyceride contents were 2.3 ± 0.4 and 1.5 ± 0.2 mmol/L in the 2.5 and 5.0 mg/kg/day HA-20 groups, lower than 6.2 ± 0.7 mmol/L in the HFHF group and 3.3 ± 0.4 mmol/L in the metformin group. Further mechanistic investigation revealed that HA-20 increased the phosphorylation of calmodulin-dependent protein kinase kinase (p-CaMKK) and the phosphorylation of AMP-activated protein kinase (p-AMPK), at least partially by increasing intracellular Ca2+ concentration, which suppressed lipogenesis and enhanced ß-oxidation. Our findings provide new insight into preventing MAFLD by increasing Ca2+ and suggest that HA-20 possesses therapeutic potential for MAFLD management.

Does Prior Stroke Predict Long-Term Recurrent Stroke After Percutaneous Coronary Intervention? Five-Year Results From a Large Cohort Study.

Background: We found a positive correlation between the prior stroke history and recurrent stroke in patients who underwent percutaneous coronary intervention (PCI) in our previous study, which indicated the close interaction of stroke and cardiovascular diseases. However, it is unclear whether prior stroke is still associated with worse prognosis at a longer follow-up period. Methods: A total of 10,724 coronary heart disease (CHD) patients who received PCI from January to December 2013 were prospectively enrolled and were subsequently divided into the prior stroke (n = 1,150) and non-prior stroke (n = 9,574) groups according to their history. Baseline characteristics and 5-year outcomes were recorded. Results: Patients with prior stroke had more clinical risk factors, as well as more extensive coronary artery lesions. Although in-hospital outcomes were similar between patients from the two groups, the 5-year follow-up result revealed that patients with prior stroke experienced higher incidence of stroke, major adverse cardiac and cerebrovascular events (MACCEs), all-cause death, and cardiac death (7.0 vs. 3.0%, p < 0.001; 25.9 vs. 20.3%, p < 0.001; 5.3 vs. 3.5%, p = 0.002; 3.1 vs. 2.1%, p = 0.032, respectively). After the propensity score matching, the 5-year stroke rate was still higher in the prior stroke group (6.8 vs. 3.4%, p = 0.001). The multivariable regression analysis also identified the prior stroke as a risk predictor of the 5-year stroke (HR = 2.011, 95% CI: 1.322-3.059, p = 0.001). Conclusions: Coronary heart disease patients with prior stroke who received PCI had a higher incidence of 5-year long-term adverse cardiovascular and cerebrovascular events, especially recurrent stroke. Prior stroke was a strong risk predictor of future stroke events.

[Infection in Children with Acute Myeloid Leukemia in the Intensive Chemotherapy Period].

OBJECTIVE: To investigate the clinical characteristics of infection in children with acute myeloid leukemia (AML) after high intensive chemotherapy， so as to provide reference for prevention and control of infection. METHODS: 56 children diagnosed as acute myeloid leukemia in our hospital from January 2016 to August 2019 were enrolled and retrospectively analyzed, the infection rate, pathogens of disease and common location of infection during the induction and consolidation period were analyzed. RESULTS: The total infection rate of the patients was 93.4%－96.4%, the average of serious infection rate was 16.0%(11.3%－19.6%), and the infection related mortality was 10.7%. Fever of unknown cause was the main reason of infection, while blood flow infections were the most common in severe infection, which were mainly caused by Gramnegative bacteria. The rate of fungal infection was 35.7% during chemotherapy. CONCLUSION: Children with AML shows a high incidence of infection in each stage of chemotherapy. The serious illness caused by blood flow infection and take antifungal drugs to reduce the occurrence of fungal infection in AML patients should be paid attention.