The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars.

Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C. eugenioides and C. canephora. The three species exhibit largely conserved genome structures between diploid parents and descendant subgenomes, with no obvious global subgenome dominance. We find evidence for a founding polyploidy event 350,000-610,000 years ago, followed by several pre-domestication bottlenecks, resulting in narrow genetic variation. A split between wild accessions and cultivar progenitors occurred ~30.5 thousand years ago, followed by a period of migration between the two populations. Analysis of modern varieties, including lines historically introgressed with C. canephora, highlights their breeding histories and loci that may contribute to pathogen resistance, laying the groundwork for future genomics-based breeding of C. arabica.

Effect of weight loss on proteinuria in adults with type 2 diabetes: A real-world study.

AIMS: To assess the impact of weight loss on proteinuria in patients with type 2 diabetes (T2DM) in real-world settings. METHODS: A total of 1054 participants were categorized based on weight change from baseline to one-year follow-up: weight gain (≥3%), stable weight, or weight loss (≥3%). Proteinuria outcomes were defined as urinary albumin/creatinine ratio (UACR) progression (≥30 % increase), UACR regression (≥30 % reduction), or UACR stable. Ordered logistic regression analysis evaluated the relationship between weight loss and UACR regression. RESULTS: Of the 1054 participants, 44.5 % were overweight, and 24.1 % were obese. Patients with obesity were at higher risk of developing proteinuria (OR, 1.783; 95 %CI, 1.195 to 2.659). Weight loss was associated with an 83.3 % increase in UACR regression compared to weight gain (OR, 1.833; 95 % CI, 1.262 to 2.663; P = 0.001). This association remained consistent across most subgroups and stronger in males (P for interaction = 0.023), with a 6 % UACR regression for every 1 kg weight loss (OR, 1.06; 95 % CI, 1.02 to 1.10; P = 0.003). CONCLUSIONS: Our real-world study reveals that weight reduction is associated with UACR regression in patients with T2DM, regardless of the approach used for weight management, and the association was much stronger in males.

Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy.

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses. RBCEVs competitively inhibit this interaction and block TIM-1-mediated viral entry into cells. We further extend the therapeutic efficacy of this antiviral treatment by loading antisense oligonucleotides (ASOs) designed to target conserved regions of key SARS-CoV-2 genes into RBCEVs. We establish that ASO-loaded RBCEVs are efficiently taken up by cells in vitro and in vivo to suppress SARS-CoV-2 replication. Our findings indicate that this RBCEV-based SARS-CoV-2 therapeutic displays promise as a potential treatment capable of inhibiting SARS-CoV-2 entry and replication.

Flavivirus genome recoding by codon optimisation confers genetically stable in vivo attenuation in both mice and mosquitoes.

Virus genome recoding is an attenuation method that confers genetically stable attenuation by rewriting a virus genome with numerous silent mutations. Prior flavivirus genome recoding attempts utilised codon deoptimisation approaches. However, these codon deoptimisation approaches act in a species dependent manner and were unable to confer flavivirus attenuation in mosquito cells or in mosquito animal models. To overcome these limitations, we performed flavivirus genome recoding using the contrary approach of codon optimisation. The genomes of flaviviruses such as dengue virus type 2 (DENV2) and Zika virus (ZIKV) contain functional RNA elements that regulate viral replication. We hypothesised that flavivirus genome recoding by codon optimisation would introduce silent mutations that disrupt these RNA elements, leading to decreased replication efficiency and attenuation. We chose DENV2 and ZIKV as representative flaviviruses and recoded them by codon optimising their genomes for human expression. Our study confirms that this recoding approach of codon optimisation does translate into reduced replication efficiency in mammalian, human, and mosquito cells as well as in vivo attenuation in both mice and mosquitoes. In silico modelling and RNA SHAPE analysis confirmed that DENV2 recoding resulted in the extensive disruption of genomic structural elements. Serial passaging of recoded DENV2 resulted in the emergence of rescue or adaptation mutations, but no reversion mutations. These rescue mutations were unable to rescue the delayed replication kinetics and in vivo attenuation of recoded DENV2, demonstrating that recoding confers genetically stable attenuation. Therefore, our recoding approach is a reliable attenuation method with potential applications for developing flavivirus vaccines.

A diagnosis model of parental care: How parents optimize their provisioning strategy in brood reduction?

Altricial birds often display biased preferences in providing parental care for their dependent offspring, especially during food shortages. During this process, such inflexible rules may result in provisioning errors. To demonstrate how parents optimize their provisioning strategies, we proposed a "diagnosis model" of parental care to posit that parents will undergo a diagnosis procedure to test whether selecting against some particular offspring based on phenotype is an optimal strategy. We tested this model in an asynchronous hatching bird, the Azure-winged Magpie Cyanopica cyanus, based on 10 years of data about demography and parental provisioning behaviors. Given their higher daily survival rates, core offspring (those hatched on the first day) merits an investment priority compared with their marginal brood mates (those hatched on later days). However, a marginal offspring also merited a priority if it displayed greater weight gain than the expected value at the early post-hatching days. Parents could detect such a marginal offspring via a diagnosis strategy, in which they provisioned the brood at the diagnosis stage by delivering food to every nestling that begged, then biased food toward high-value nestlings at the subsequent decision stage by making a negative response to the begging of low-value nestlings. In this provisioning strategy, the growth performance of a nestling became a more reliable indicator of its investment value than its hatching order or competitive ability. Our findings provide evidence for this "diagnosis model of parental care" wherein parents use a diagnosis method to optimize their provisioning strategy in brood reduction.

Interrelation between the lipid accumulation product index and diabetic kidney disease in patients with type 2 diabetes mellitus.

Objective: The purpose of this study was to determine the relation between the lipid accumulation product index (LAPI) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: Herein, 931 patients were enrolled and their data were collected. Then the interrelation between LAPI and DKD was assessed using multivariate logistic regression analyses (LRAs) and by a restricted cubic spline (RCS). Results: In total, 931 participants (352 females and 579 males) aged 55 years on average were included in the study. After adjusting for several confounders, the odds ratio for DKD was increased evidently in the third LAPI tertile compared with that in the first LAPI tertile. In addition, the RCS revealed a positive interrelation between LAPI and DKD. In the subgroup analyses, age, sex, hyperlipidemia, hypertension, and HbA1c did not significantly interact with LAPI. Conclusions: LAPI was higher in the DKD group than in the no-DKD group, and LAPI is positively linked with DKD, which may have potential value to diagnose DKD in clinical practice.

Construction and pattern optimization of ecological network in Zhengzhou metropolitan area.

The rapid urbanization process has led to the increasingly prominent problems of ecological environment protection and optimization. The construction of ecological network system, planning to guide ecological values, and efficiently utilizing landscape effects are of great significance for regional regulation of ecological space and promotion of local sustainable development. Taking Zhengzhou metropolitan area as an example, based on land use data at eight time points from 1980 to 2020, using ArcGIS, Guidos Toolbox, Conefor and other tools, we outlined the ecological network with a high structural integrity in the study area. We used future land use simulation to predict future land pattern, morphological spatial pattern analysis to identify landscape elements, minimum cumulative resistance to construct comprehensive resistance surface, gravity model to calculate ecological gravity, hydrologic analysis to create resistance paths, and network structure evaluation, etc. The results showed that, among the nine source sites in the study area, the ecological sources in the Yellow River Basin connected the large-scale centralized source areas in the east and west of the network. The rest sources were located in the northeast, southeast, and southwest of the study area, which were distributed in a semi-circumferential manner around the main urban area of Zhengzhou. There were a total of 163 minimum cost paths and 58 ecological corridors, of which 10, 19 and 29 were primary, secondary and tertiary corridors, respectively, in the form of "three horizontals and three verticals" and "point-axis" along the Yellow River Basin distribution was dominant. A total of 70 ecological nodes were recored in the study area, which were divided into strategic points (10), natural ecological points (27) and artificial environment points (33). Those ecological nodes were distributed in key nodes such as the core of each source area and the intersection of corridors location. The ecological network included all the landscape elements in the study area and connected the main ecological substrates in a horizontal "C" shape. The overall performance was a semi-enclosed network structure of "one horizontal, two verticals and four groups".

Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants.

The COVID-19 pandemic has brought about unprecedented medical and healthcare challenges worldwide. With the continual emergence and spread of new COVID-19 variants, four drug compound libraries were interrogated for their antiviral activities against SARS-CoV-2. Here, we show that the drug screen has resulted in 121 promising anti-SARS-CoV-2 compounds, of which seven were further shortlisted for hit validation: citicoline, pravastatin sodium, tenofovir alafenamide, imatinib mesylate, calcitriol, dexlansoprazole, and prochlorperazine dimaleate. In particular, the active form of vitamin D, calcitriol, exhibits strong potency against SARS-CoV-2 on cell-based assays and is shown to work by modulating the vitamin D receptor pathway to increase antimicrobial peptide cathelicidin expression. However, the weight, survival rate, physiological conditions, histological scoring, and virus titre between SARS-CoV-2 infected K18-hACE2 mice pre-treated or post-treated with calcitriol were negligible, indicating that the differential effects of calcitriol may be due to differences in vitamin D metabolism in mice and warrants future investigation using other animal models.

Infection with wild-type SARS-CoV-2 elicits broadly neutralizing and protective antibodies against omicron subvariants.

The omicron variants of SARS-CoV-2 have substantial ability to escape infection- and vaccine-elicited antibody immunity. Here, we investigated the extent of such escape in nine convalescent patients infected with the wild-type SARS-CoV-2 during the first wave of the pandemic. Among the total of 476 monoclonal antibodies (mAbs) isolated from peripheral memory B cells, we identified seven mAbs with broad neutralizing activity to all variants tested, including various omicron subvariants. Biochemical and structural analysis indicated the majority of these mAbs bound to the receptor-binding domain, mimicked the receptor ACE2 and were able to accommodate or inadvertently improve recognition of omicron substitutions. Passive delivery of representative antibodies protected K18-hACE2 mice from infection with omicron and beta SARS-CoV-2. A deeper understanding of how the memory B cells that produce these antibodies could be selectively boosted or recalled can augment antibody immunity against SARS-CoV-2 variants.

Broadly neutralizing and protective nanobodies against SARS-CoV-2 Omicron subvariants BA.1, BA.2, and BA.4/5 and diverse sarbecoviruses.

As SARS-CoV-2 Omicron and other variants of concern (VOCs) continue spreading worldwide, development of antibodies and vaccines to confer broad and protective activity is a global priority. Here, we report on the identification of a special group of nanobodies from immunized alpaca with potency against diverse VOCs including Omicron subvariants BA.1, BA.2 and BA.4/5, SARS-CoV-1, and major sarbecoviruses. Crystal structure analysis of one representative nanobody, 3-2A2-4, discovers a highly conserved epitope located between the cryptic and the outer face of the receptor binding domain (RBD), distinctive from the receptor ACE2 binding site. Cryo-EM and biochemical evaluation reveal that 3-2A2-4 interferes structural alteration of RBD required for ACE2 binding. Passive delivery of 3-2A2-4 protects K18-hACE2 mice from infection of authentic SARS-CoV-2 Delta and Omicron. Identification of these unique nanobodies will inform the development of next generation antibody therapies and design of pan-sarbecovirus vaccines.

Early pathogenesis profiles across SARS-CoV-2 variants in K18-hACE2 mice revealed differential triggers of lung damages.

The on-going COVID-19 pandemic has given rise to SARS-CoV-2 clades and variants with differing levels of symptoms and severity. To this end, we aim to systematically elucidate the changes in the pathogenesis as SARS-CoV-2 evolved from ancestral to the recent Omicron VOC, on their mechanisms (e.g. cytokine storm) resulting in tissue damage, using the established K18-hACE2 murine model. We reported that among the SARS-CoV-2 viruses tested, infection profiles were initially similar between viruses from early clades but started to differ greatly starting from VOC Delta, where the trend continues in Omicron. VOCs Delta and Omicron both accumulated a significant number of mutations, and when compared to VOCs Alpha, Beta, and earlier predecessors, showed reduced neurotropism and less apparent gene expression in cytokine storm associated pathways. They were shown to leverage on other pathways to cause tissue damage (or lack of in the case of Omicron). Our study highlighted the importance of elucidating the response profiles of individual SARS-CoV-2 iterations, as their propensity of severe infection via pathways like cytokine storm changes as more variant evolves. This will then affect the overall threat assessment of each variant as well as the use of immunomodulatory treatments as management of severe infections of each variant.

Association between Chinese visceral adiposity index and metabolic-associated fatty liver disease in Chinese adults with type 2 diabetes mellitus.

Objective: The purpose of the study was to determine the correlation of the Chinese visceral adiposity index (CVAI) with metabolic-associated fatty liver disease (MAFLD) in Chinese adults with type 2 diabetes mellitus (T2DM). Materials/methods: In this cross-sectional study, data on sociodemographic characteristics, laboratory test results, coexisting diseases, and medical therapy were collected and analyzed. Multivariate logistic regression analyses were used to examine the correlation between CVAI and MAFLD. In order to investigate the correlation between CVAI on a continuous scale and MAFLD, a restricted cubic spline (RCS) was used. Results: A total of 679 participants were included in this study. There were 251 female participants and 428 male participants, with a median age of 55 years. In the multivariate logistic regression model, diastolic blood pressure, duration of diabetes, glycated hemoglobin, hemoglobin, alanine transaminase, aspartate aminotransferase, gamma -glutamyl transferase, albumin, blood urea nitrogen, total cholesterol, low-density lipoprotein cholesterol, statin use and metformin use were adjusted, and an evident increase in the odds ratios of MAFLD from the lowest to the highest CVAI quartile was found (P value for trend < 0.001). Moreover, the RCS curves revealed a positive correlation between CVAI and MAFLD. Conclusions: The CVAI is positively correlated with MAFLD and may be an indicator with diagnostic value for MAFLD in clinical practice in type 2 diabetic patients.

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes.

Objective: Patients with type 2 diabetes have a high risk of non-alcoholic fatty liver disease (NAFLD) and related liver fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated efficacy in improving NAFLD, while their effectiveness on liver fibrosis is limited in type 2 diabetic patients. Materials/Methods: A prospective cohort study was performed in type 2 diabetic patients. The study subjects were divided into two groups based on the use of liraglutide or not, and propensity score matching (PSM) was also conducted. After 12 months follow-up, liver fibrosis was assessed by NAFLD fibrosis score (NFS) fibrosis-4 (FIB-4), and liver stiffness measurement (LSM). The association between liraglutide use and liver fibrosis was analyzed by multivariable linear regression. Results: In the current study, a total of 1,765 type 2 diabetic patients were enrolled. 262 patients were liraglutide user and 1,503 were nouser. After 12 months follow-up, liraglutide use tended to be associated with reduced prevalence of advanced fibrosis (3.1% vs. 6.1%, P = 0.218). After adjustment for confounding factors, multivariable linear regression revealed that liraglutide use was negatively associated with decreased NFS (ß= -0.34, P = 0.043), FIB4 (ß= -0.26, P = 0.044) and LSM (ß= -4.95, P = 0.007) in type 2 diabetics. The results after PSM were similar to those before PSM. Conclusions: Liraglutide treatment is associated with decreased liver fibrosis in type 2 diabetic subjects.

SARS-CoV-2 Omicron Variants Reduce Antibody Neutralization and Acquire Usage of Mouse ACE2.

Striking number of mutations found in the spike protein of recently emerged SARS-CoV-2 Omicron subvariants BA.1, BA.2, BA.3 and BA.4/5 has raised serious concerns regarding the escape from current antibody therapies and vaccine protection. Here, we conducted comprehensive analysis on the extent of two major Omicron lineages BA.1/BA.1.1 and BA.2 to escape neutralization from the therapeutic antibodies approved by the regulatory authorities and convalescent plasma from SARS-CoV-2 patients infected during initial wave of pandemic in early 2020. We showed that Omicron BA.1/BA.1.1 were the most resistant in both magnitude and breadth against antibodies and convalescent plasma, followed by Beta, BA.2, Gamma, Delta and Alpha. While the majority of therapeutic antibodies lost binding and neutralization to Omicron variants, BRII combo (BRII-196 + BRII-198), S309, and AZ combo (COV2-2196 + COV2-2130) maintained neutralization despite of reduction due to either conserved epitope or combinational effect between the two designated antibodies. A single intraperitoneal injection of BRII combo as a prophylactic treatment protected animals from Omicron infection. Treated animals manifested normal body weight, survived infection up to 14 days, undetectable levels of infectious viruses in the lungs, and reduced lung pathology compared to the controls. Analyzing ACE2 from diverse host species showed that Omicron variants acquired ability to use mouse ACE2 for entry. These results demonstrate major antigenic shifts and potentially broadening the host range of two major Omicron lineages BA.1/BA.1.1 and BA.2, posing serious challenges to current antibody therapies and vaccine protection as well as increasing danger of spillover into the wildlife.

Association Between High-Sensitivity C-Reactive Protein and Diabetic Kidney Disease in Patients With Type 2 Diabetes Mellitus.

Objective: High-sensitivity C-reactive protein (hs-CRP) is an inflammatory marker. This study aimed to identify the correlation between hs-CRP levels and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Materials/Methods: This cross-sectional and observational study included 927 patients with T2DM. We collected the data of patients based on their medical data, including sociodemographic characteristics, concomitant diseases, laboratory results, and medical therapy. Multivariate logistic regression analysis was conducted to assess the relationship between hs-CRP levels and DKD. A restricted cubic spline (RCS) was used to assess the correlation of hs-CRP levels on a continuous scale with the DKD. Results: In total, 927 patients were recruited in our study. The median age of the recruited patients was 55 years, and there were 346 female patients and 581 male patients. The hs-CRP levels were evidently higher in patients with DKD than those without DKD. After adjusting for age, sex, diastolic blood pressure, systolic blood pressure, body mass index, neck circumference, waist circumference, hypertension, duration of diabetes, common carotid artery plaque, fasting plasma glucose, glycated hemoglobin, hemoglobin, erythrocyte, leukocyte, γ-glutamyl transferase, albumin, urea nitrogen, uric acid and triglyceride, a significant increase in the odds ratios (ORs) for DKD in the fourth hs-CRP quartile compared with the first quartile was observed (P value for trend= 0.003), and the ORs (95% confidence intervals) in the fourth quartile of hs-CRP were 1.968 (1.244-3.114) for DKD compared to the first quartile.. Moreover, the RCS curves presented a positive association between hs-CRP and DKD in total subjects, male subjects and female subjects, respectively. Conclusions: The results of our study indicated that hs-CRP levels were significantly and positively correlated with the presence of DKD, which may provide predictive and diagnostic values in clinical practice.

A stratified analysis of a deep learning algorithm in the diagnosis of diabetic retinopathy in a real-world study.

BACKGROUND: The aim of our research was to prospectively explore the clinical value of a deep learning algorithm (DLA) to detect referable diabetic retinopathy (DR) in different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, glycosylated hemoglobin (HbA1c), diabetes duration, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR) at a real-world diabetes center in China. METHODS: A total of 1147 diabetic patients from Shanghai General Hospital were recruited from October 2018 to August 2019. Retinal fundus images were graded by the DLA, and the detection of referable DR (moderate nonproliferative DR or worse) was compared with a reference standard generated by one certified retinal specialist with more than 12 years of experience. The performance of DLA across different subgroups stratified by types of diabetes, blood pressure, sex, BMI, age, HbA1c, diabetes duration, UACR, and eGFR was evaluated. RESULTS: For all 1674 gradable images, the area under the receiver operating curve, sensitivity, and specificity of the DLA for referable DR were 0.942 (95% CI, 0.920-0.964), 85.1% (95% CI, 83.4%-86.8%), and 95.6% (95% CI, 94.6%-96.6%), respectively. The DLA showed consistent performance across most subgroups, while it showed superior performance in the subgroups of patients with type 1 diabetes, UACR ≥ 30 mg/g, and eGFR < 90 mL/min/1.73m2 . CONCLUSIONS: This study showed that the DLA was a reliable alternative method for the detection of referable DR and performed superior in patients with type 1 diabetes and diabetic nephropathy who were prone to DR.

A Potent and Protective Human Neutralizing Antibody Against SARS-CoV-2 Variants.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge and spread around the world, antibodies and vaccines to confer broad and potent neutralizing activity are urgently needed. Through the isolation and characterization of monoclonal antibodies (mAbs) from individuals infected with SARS-CoV-2, we identified one antibody, P36-5D2, capable of neutralizing the major SARS-CoV-2 variants of concern. Crystal and electron cryo-microscopy (cryo-EM) structure analyses revealed that P36-5D2 targeted to a conserved epitope on the receptor-binding domain of the spike protein, withstanding the three key mutations-K417N, E484K, and N501Y-found in the variants that are responsible for escape from many potent neutralizing mAbs, including some already approved for emergency use authorization (EUA). A single intraperitoneal (IP) injection of P36-5D2 as a prophylactic treatment completely protected animals from challenge of infectious SARS-CoV-2 Alpha and Beta. Treated animals manifested normal body weight and were devoid of infection-associated death up to 14 days. A substantial decrease of the infectious virus in the lungs and brain, as well as reduced lung pathology, was found in these animals compared to the controls. Thus, P36-5D2 represents a new and desirable human antibody against the current and emerging SARS-CoV-2 variants.

Fitness consequences of divorce in the azure-winged magpie depends on the breeding experience of a new mate.

Sexual conflict in producing and raising offspring is a critical issue in evolutionary ecology research. Individual experience affects their breeding performance, as measured by such traits of provisioning of offspring and engagement in extra-pair copulations, and may cause an imbalance in sexual conflict. Thus, divorce is hypothesized to occur within aged social pairs, irrespective of current reproductive success. This concept was explored in the azure-winged magpie Cyanopica cyanus by investigating the divorce of a social pair and its relationship to their changes in breeding performance with prior experience. Females engaging in extra-pair copulation may intensify sexual conflicts and may be the main reason for divorce. Once divorced, females repairing with an inexperienced male realized higher reproductive success than that repairing with an experienced male; males repairing with an experienced female realized higher reproductive success than that repairing with an inexperienced female. This finding indicates that the fitness consequence of divorce depends on the breeding experience of new mates. Divorced females can obtain more extra-pair copulations, whereas divorced males cannot, when they repair with inexperienced breeders. Divorced females provisioned a brood at lower rates than inexperienced females whereas divorced males had no such difference. It appears that divorced females can obtain an advantage in sexual conflicts with inexperienced mates in future reproduction. Consequently, females are probably more active than males in divorcing their aged mates so as to select an inexperienced male as a new mate. Azure-winged magpies thus provide novel insights into the implications of sexual conflict in birds.

Interferon-α may help prevent molecular relapse of chronic myeloid leukemia after the discontinuation of tyrosine kinase inhibitors.

BACKGROUND: Currently, the goal of chronic myeloid leukemia (CML) treatment is normal survival and good quality of life without life-long treatment, namely, "treatment-free remission" (TFR). At present, approximately only 50% of patients with CML with a deep molecular response are able to discontinue tyrosine kinase inhibitor (TKI) without experiencing molecular relapse [MR; loss of major molecular response (MMR)]. In addition, prior interferon (IFN) treatment is associated with a higher rate of TFR. METHODS: We aimed to evaluate the feasibility of TKI discontinuation in Chinese patients with CML and determine whether IFN could prevent MR when used after TKI discontinuation in patients with 0.0032%

Association of the Non-Alcoholic Fatty Liver Disease Fibrosis Score with subclinical myocardial remodeling in patients with type 2 diabetes: A cross-sectional study in China.

AIMS/INTRODUCTION: Non-alcoholic fatty liver disease, especially with liver fibrosis, is associated with cardiovascular diseases. The Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS), a non-invasive marker of advanced fibrosis, was found to be associated with cardiovascular diseases in different populations. The aim of the present study was to determine whether the NFS is associated with subclinical myocardial remodeling in type 2 diabetes patients. MATERIALS AND METHODS: A cross-sectional study was carried out in type 2 diabetes patients. The NFS derived from available parameters was calculated, and the participants were divided according to the quartiles of the NFS and grades of the NFS (low, intermediate and high). Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index, another two liver fibrosis scores, were also calculated. Subclinical myocardial remodeling was examined by echocardiography, and its associations with NFS, Fibrosis-4 and Aspartate Aminotransferase to Platelet Ratio Index were analyzed. RESULTS: A total of 1,878 type 2 diabetes patients were enrolled in the present study. The NFS was independently associated with sex, age, body mass index, low-density lipoprotein cholesterol and glycated hemoglobin in type 2 diabetes patients. Parameters of subclinical myocardial remodeling including left atrial dimension, interventricular septum thickness, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular posterior wall thickness (LVPWT) and left ventricular mass index were all gradually increased with the increment of the NFS. Linear regression analysis further showed that the NFS was positively associated with left atrial dimension, interventricular septum thickness, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, LVPWT and left ventricular mass index after adjustment for the confounding factors. Similarly, Fibrosis-4 was associated with left atrial dimension, interventricular septum thickness, LVPWT and left ventricular mass index. In contrast, the Aspartate Aminotransferase to Platelet Ratio Index was only associated with LVPWT. CONCLUSIONS: Non-invasive liver fibrosis scores, especially the NFS, are independently associated with subclinical myocardial remodeling in type 2 diabetes patients.