RESUMEN
In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.
RESUMEN
The fate of sedimentary nitrogen during subduction is essential for understanding the origin of nitrogen in the deep Earth. Here we study the behavior of nitrogen in slab sediments during the phengite to K-hollandite transition at 10-12 GPa and 800-1100 °C. Phengite stability is extended by 1-3 GPa in the nitrogen (NH4+)-bearing system. The phengite-fluid partition coefficient of nitrogen is 0.031 at 10 GPa, and K-hollandite-fluid partition coefficients of nitrogen range from 0.008 to 0.064, showing a positive dependence on pressure but a negative dependence on temperature. The nitrogen partitioning data suggest that K-hollandite can only preserve ~43% and ~26% of the nitrogen from phengite during the phengite to K-hollandite transition along the cold and warm slab geotherms, respectively. Combined with the slab sedimentary nitrogen influx, we find that a maximum of ~1.5 × 108 kg/y of nitrogen, representing ~20% of the initial sedimentary nitrogen influx, could be transported by K-hollandite to the lower mantle. We conclude that slab sediments may have contributed less than 15% of the lower mantle nitrogen, most of which is probably of primordial origin.
RESUMEN
BACKGROUND: The intrapapillary capillary loop (IPCL) characteristics, visualized using magnifying endoscopy, are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma (ESCC). Japan Esophageal Society (JES) classification is the most widely used classification. Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor: tortuosity, dilatation, irregular caliber, and different shapes. However, the pathological characteristics of IPCLs have not been thoroughly investigated, especially the microvascular structures corresponding to the deepest parts of the lesions' infiltration. AIM: To investigate differences in pathological microvascular structures of ESCC, which correspond to the deepest parts of the lesions' infiltration. METHODS: Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023. Patients first underwent magnified endoscopic examination, followed by endoscopic submucosal dissection or surgical treatment. Pathological images were scanned using a three-dimensional slice scanner, and the pathological structural differences in different types, according to the JES classification, were analyzed using nonparametric tests and t-tests. RESULTS: The 35 lesions were divided into four groups according to the JES classification: A, B1, B2, and B3. Statistical analyses revealed significant differences (a P < 0.05) in the short and long calibers, area, location, and density between types A and B. Notably, there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3 (P > 0.05). However, significant differences in the short calibers, long calibers, and area of IPCL were observed between types B1 and B3 (a P < 0.05); no significant differences were found in the density or location (P > 0.05). CONCLUSION: Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy, especially between the types A and B.
RESUMEN
BACKGROUND: Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell-derived exosome nebulization therapy (SCENT). METHODS: Stem cell-derived exosomes were characterized for size distribution and surface markers. C57BL/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging. RESULTS: Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of Cd36 in endothelial cells (ECs). In an EC-Cd36fl/- conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (Δ=11.66±5.12%) and fractional shortening (Δ=5.72±2.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall. CONCLUSIONS: In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC-Cd36fl/- mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.
Asunto(s)
Exosomas , Ratones Endogámicos C57BL , Infarto del Miocardio , Animales , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/terapia , Infarto del Miocardio/fisiopatología , Exosomas/metabolismo , Ratones , Administración por Inhalación , Modelos Animales de Enfermedad , Porcinos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Masculino , Función Ventricular Izquierda , Humanos , Miocardio/metabolismo , Miocardio/patología , Células Madre/metabolismo , Antígenos CD36/metabolismo , Antígenos CD36/genéticaRESUMEN
Flexible conductive hydrogels have revolutionized the lives and are widely applied in health monitoring and wearable electronics as a new generation of sensing materials. However, the inherent low mechanical strength, sensitivity, and lack of rapid self-healing capacity results in their short life, poor detection accuracy, and environmental pollution. Inspired by the molecular structure of bone and its chemical characteristics, a novel fully physically cross-linked conductive hydrogel is fabricated by the introduction of nanohydroxyapatite (HAp) as the dynamic junction points. In detail, the dynamically cross-linked network, including multiple physical interactions, provides it with rapid self-healing ability and excellent mechanical properties (elongation at break (>1200%), tensile strength (174kPa), and resilience (92.61%)). Besides, the ions (Cl-, Li+, Ca2+) that move freely within the system impart outstanding electrical conductivity (2.46 ± 0.15 S m-1), high sensitivity (gauge factor, GF>8), good antifreeze (-40.2 °C), and humidity properties. The assembled sensor can be employed to sensitively detect various large human motions and subtle changes in behavior (facial expressions, speech recognition). Meanwhile, the hydrogel sensor can also degrade in phosphate-buffered saline solution without causing any environmental pollution. Therefore, the designed hydrogels may become a promising candidate material in the future potential applications for smart wearable sensors and electronic skin.
RESUMEN
The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPePV) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTADA) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPePV cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPePV cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPePV cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder.
RESUMEN
Ammonia (NH3) slip from diesel vehicle aftertreatment systems and internal combustion engines fueled by NH3 or NH3/H2 poses serious environmental problems. Ag-based catalysts are widely used for the selective catalytic oxidation of NH3 to N2 (NH3-SCO), and their performance is greatly dependent on the state of Ag, which is influenced by the anchoring sites on the support. Despite efforts to identify the direct anchoring sites of metal atoms on TiO2, conflicting views persist. Here, we compared the correlation between Ag dispersion and the content of hydroxyl (OH) groups or defects on TiO2 and conducted density functional theory (DFT) calculations, and the results confirmed that the surface OH groups of TiO2 serve as the direct anchoring sites for Ag. By modulating the OH group content through thermal induction, the optimal OH group content on TiO2-800 resulted in more metallic Ag nanoparticles (Ag0 NPs) in larger sizes, leading to the development of an excellent NH3-SCO catalyst. Moreover, in situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), kinetic studies, and DFT calculations suggested that more Ag0 NPs in larger sizes on 10Ag/TiO2-800 were conducive to O2 activation and NH3 dissociation. Our findings provide new insights for designing efficient NH3-SCO catalysts, and OH groups as direct anchoring sites could be extended to other metals and supports for the rational design of catalysts.
RESUMEN
Herein, poly(pentanediamine terephthalamide) (PA5T) homopolymer was synthesized via a salt-forming reaction+solid state polycondensation method using bio-based 1,5-pentanediamine and terephthalic acid as the primary raw materials. To address the issue of its narrower processing window, poly(hexamethylene terephthalamide)(PA6T), which also cannot be melt processed due to the processing window is negative, was introduced into its molecular chain to synthesize poly (pentanediamine/hexanediamine terephthaloyl) (PA5T-co-6T) copolymers. The structures were investigated by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance carbon spectroscopy (13C-NMR). Furthermore, the melting temperature, crystallization temperature, thermal stability, and crystal growth mode of the polymer were tested and analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and wide-angle x-ray diffraction (WAXD), respectively. The results demonstrate that the crystal growth mode gradually changes from three-dimensional spherical growth to two-dimensional disk-like or three-dimensional spherical growth with the increase of 6T chain segment content. Simultaneously, the crystallization temperature, melting temperature, and crystallization rate of the polymer all showed a trend of decreasing first and then increasing, which was due to the combined effects of the increase in the content of 6T chain segments on the molecular-chain structure and crystal structure of the polymer. Bio-based PA5T-co-6T has excellent heat resistance and a wider processing window than PA5T and PA6T, which possesses great application prospects in the fields of automotive, electronic appliances, and LED optics.
RESUMEN
Studies have shown that decreased expression of glucose-6-phosphate dehydrogenase (G6PD) play an important role in DKD. However, the upstream and downstream pathways of G6PD downregulation leading to DKD have not been elucidated.We conducted a series of studies including clinical study, animal studies, and in vitro studies to explore this. Firstly, a total of 90 subjects were evaluated. The urinary G6PD activity and its association with the clinical markers were analyzed. Then, urine differentially microRNAs that can bind and degrade G6PD were screened and verified in DKD patients. After that, high glucose (HG)-cultured Human kidney cells (HK-2) and Zucker diabetic fatty (ZDF) rats were used to test the roles of miR-7977/G6PD/albumin-induced autophagy in DKD. The plasma and urinary G6PD activity were decreased significantly in patients with DKD, accompanied by increased urinary mir-7977 level. The fasting plasma glucose (FPG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and urinary albumin excretion were independent predictors of urinary G6PD activity by multiple linear regression analysis.The increased expression of miR-7977 and decreased expression of G6PD were also found in the kidney of ZDF rats with early renal tubular damage.In HK-2 cells cultured with normal situation, low level of albumin could induce autophagy along with the stimulation of G6PD although this was impaired under high glucose. Overexpression of G6PD reversed albumin-induced autophagy in HK2 cells under high glucose.Inhibition mir-7977 expression led to significantly increased expression of G6PD and reversed the effects of high glucose on albumin induced autophagy.Our study supports a new mechanism of G6PD downregulation in DKD.
RESUMEN
Molecular tunneling junctions based on self-assembled monolayers (SAMs) have demonstrated rectifying characteristics at the nanoscale that can hardly be achieved using traditional approaches. However, defects in SAMs result in high leakage when applying bias. The poor performance of molecular diodes compared to silicon or thin-film devices limits their further development. In this study, we show that incorporating "mixed backbones" with flexible-rigid structures into molecular junctions can dynamically block tunneling currents, which is difficult to realize using non-molecular technology. Our idea is achieved by the interaction between interfacial dipole moments and electric field, triggering structured packing in SAMs. Efficient blocking of leakage by more than an order of magnitude leads to a significant enhancement of the rectification ratio to the initial value. The rearrangement of supramolecular structures has also been verified through electrochemistry and electroluminescence measurements. Moreover, the enhanced rectification is extended to various challenging environments, including endurance measurements, bending of electrodes, and rough electrodes, thus demonstrating the feasibility of the dynamic behavior of molecules for practical electronic applications.
RESUMEN
Gastric intestinal metaplasia (GIM) represents a precancerous stage characterized by morphological and pathophysiological changes in the gastric mucosa, where gastric epithelial cells transform into a phenotype resembling that of intestinal cells. Previous studies have demonstrated that the intragastric administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) induces both gastric carcinoma and intestinal metaplasia in mice. Here, we show that MNNG induces GIM in three-dimensional (3D) mouse organoids. Our histological analyses reveal that MNNG-induced gastric organoids undergo classical morphological alterations, exhibiting a distinct up-regulation of CDX2 and MUC2, along with a down-regulation of ATP4B and MUC6. Importantly, metaplastic cells observed in MNNG-treated organoids originate from MIST1+ cells, indicating their gastric chief cell lineage. Functional analyses show that activation of the RAS signaling pathway drives MNNG-induced metaplasia in 3D organoids, mirroring the characteristics observed in human GIM. Consequently, modeling intestinal metaplasia using 3D organoids offers valuable insights into the molecular mechanisms and spatiotemporal dynamics of the gastric epithelial lineage during the development of intestinal metaplasia within the gastric mucosa. We conclude that the MNNG-induced metaplasia model utilizing 3D organoids provides a robust platform for developing preventive and therapeutic strategies to mitigate the risk of gastric cancer before precancerous lesions occur.
RESUMEN
BACKGROUND: With the popularization of computed tomography, more and more pulmonary nodules (PNs) are being detected. Risk stratification of PNs is essential for detecting early-stage lung cancer while minimizing the overdiagnosis of benign nodules. This study aimed to develop a circulating tumor DNA (ctDNA) methylation-based, non-invasive model for the risk stratification of PNs. METHODS: A blood-based assay ("LUNG-TRAC") was designed to include novel lung cancer ctDNA methylation markers identified from in-house reduced representative bisulfite sequencing data and known markers from the literature. A stratification model was trained based on 183 ctDNA samples derived from patients with benign or malignant PNs and validated in 62 patients. LUNG-TRAC was further single-blindly tested in a single- and multi-center cohort. RESULTS: The LUNG-TRAC model achieved an area under the curve (AUC) of 0.810 (sensitivity = 74.4 % and specificity = 73.7 %) in the validation set. Two test sets were used to evaluate the performance of LUNG-TRAC, with an AUC of 0.815 in the single-center test (N = 61; sensitivity = 67.5 % and specificity = 76.2 %) and 0.761 in the multi-center test (N = 95; sensitivity = 50.7 % and specificity = 80.8 %). The clinical utility of LUNG-TRAC was further assessed by comparing it to two established risk stratification models: the Mayo Clinic and Veteran Administration models. It outperformed both in the validation and the single-center test sets. CONCLUSION: The LUNG-TRAC model demonstrated accuracy and consistency in stratifying PNs for the risk of malignancy, suggesting its utility as a non-invasive diagnostic aid for early-stage peripheral lung cancer. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov (NCT03989219).
RESUMEN
Biologic agents have become a mainstay in the treatment of psoriasis, particularly in moderate to severe, refractory, and special types of the disease. Among these, ixekizumab is a humanized IgG4 monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate to severe plaque psoriasis. Its adverse effects include infections such as nasopharyngitis, upper respiratory tract infections, and injection site reactions. While the incidence of tuberculosis (TB) associated with IL-17A antagonists is extremely low, this paper reports a case of active pulmonary tuberculosis occurring after ten doses of ixekizumab treatment for chronic plaque psoriasis. This highlights the importance for clinicians to remain vigilant regarding tuberculosis infection in patients undergoing therapy with this class of medications, emphasizing the need for enhanced screening and monitoring for tuberculosis during treatment.
RESUMEN
BACKGROUND/AIMS: Homocysteine (Hcy) has been associated with an increased risk of diabetic nephropathy (DN) in patients, but there is still controversy. This study aims to investigate the causal relationship between plasma Hcy and DN. METHODS: A Mendelian randomization (MR) study using data from 2 samples was employed to infer causal relationships. The aggregated genetic data associated with Hcy was derived from the largest genome-wide association study (GWAS) to date, involving 44,147 individuals of European ancestry.Data on SNP-diabetic nephropathy, creatinine, and urea nitrogen were obtained from the IEU GWAS database. The analysis method employed a fixed-effect or random-effect inverse variance-weighted approach to estimate effects.Additional analysis methods were used to assess stability and sensitivity. The potential for pleiotropy was evaluated using the MR-Egger intercept test. RESULTS: Using 12 SNPs as instrumental variables, two-sample MR analysis revealed no evidence of a causal relationship between genetically predicted plasma Hcy levels and diabetic nephropathy, as well as creatinine and blood urea nitrogen levels. This finding is consistent with the results obtained from other testing methods. CONCLUSIONS: Two-sample Mendelian Randomization analysis found no evidence of a causal relationship between plasma homocysteine levels and diabetic nephropathy, creatinine, or urea.
RESUMEN
BACKGROUND: Vibrotactile stimulation has been studied in its efficacy of reducing freezing of gait (FOG) in patients with Parkinson's disease (PD). However, the results are still controversial. We evaluated the efficacy of a newly developed vibrotactile foot device on freezing severity and gait measures in PD patients with FOG. OBJECTIVE: To evaluate the efficacy of vibrotactile foot device on PD patients with FOG. METHODS: Thirty-three PD patients with FOG were examined during their "off" medication state. The efficacy of the vibrotactile foot device was evaluated using a gait protocol comprising walking trials with vibrotactile stimulation "off" and "on." Walking trials were videotaped for the offline rating by two movement disorder specialists. The Opal inertial sensor unit (128 Hz; Mobility Lab; APDM Inc., Portland, OR, USA) was used for quantitative gait analysis. RESULTS: The results demonstrated 33.1% reduction in number of FOG episodes (P < 0.001) and 32.6% reduction of freezing episodes (P < 0.001). Quantitative gait analysis showed a significant increase in step length (P = 0.033). A moderate negative correlation was observed between the change of percent time frozen and age (r = -0.415, P = 0.016). 73% of participants reported minimal to substantial improvement in walking with this vibrating stimulation delivered by the vibrotactile foot device. CONCLUSIONS: The vibrotactile foot device is an efficient device that could significantly reduce freezing severity and provide gait regulation to patients with PD experiencing frequent freezing. It could potentially be used in the home environment for improving the quality of life.
RESUMEN
BACKGROUND: The severity and treatment response of acne, melasma, and rosacea may be influenced by various currently unclear internal and external factors. This study aimed to provide evidence to the influencing factors for the mentioned conditions through a real-world case-control study. METHODS: An online survey consisting of 60 questions was implemented, collecting information on demographics, socioeconomics, genetic factors, lifestyle habits, environmental exposures, and skin care behaviors. Then we constructed univariate and multivariate logistic regressions. Furthermore, we analyzed the dose-response relationship between exposure and outcome. RESULTS: A total of 399 individuals, including 94 acne patients, 107 melasma patients, and 91 rosacea patients were included. Acne and melasma were positively correlated with screen time (acne: odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.25-4.02; melasma: OR: 1.59, 95% CI: 1.09-2.31), while exercise exerted a protective effect on both acne (OR: 0.31, 95% CI: 0.13-0.77) and melasma (OR: 0.42, 95% CI: 0.22-0.80) in a dose-response relationship. In addition, males were associated with an elevated risk of acne (OR: 6.62, 95% CI: 1.01-43.26). Aging (OR: 1.15, 95% CI: 1.07-1.24) and irregular bowel movements (OR: 2.99, 95% CI: 1.11-8.08) were independent risk factors for melasma. Rosacea was positively associated with BMI (OR: 1.17, 95% CI: 1.01-1.35). CONCLUSION: In our study, we highlighted exercise as an independent protective factor for both acne and melasma in a dose-response trend. Inversely, extended use of electronic equipment was independently associated with higher risks of acne and melasma. Rosacea, however, was more likely to be related with BMI.
RESUMEN
Purpose: This study aimed to compare the risk of vagal reflex during microsurgical subinguinal varicocelectomy (MSV) under general anesthesia (GA) with or without additional local anesthetic (LA) spermatic cord block (SCB). Method: A single-center randomized controlled trial was conducted between January 2022 and June 2023.300 patients with left-sided grade â ¢ varicocele were randomly divided into two groups: SCB group (n = 153) and control group (n = 147)ï¼computer-generated random numbers listï¼. During MSV under GA, the SCB group was given of ropivacaine for SCB before pulling the spermatic cord, while the control group was directly lifted. The primary outcome was the reduction in the lowest heart rate in the SCB group as compared with the control group during spermatic cord traction (SCT). Secondary outcomes included the reduction in the lowest blood pressure in the SCB group as compared with the control group; and the reductions in the lowest heart rate and lowest blood pressure as compared with baseline during SCT. The number of times that surgery and medications were suspended because of symptomatic reflex bradycardia was also recorded. Adverse events were also recorded as secondary outcomes. Result: Five patients in the SCB group and 10 patients in the CG were excluded. The lowest heart rate and systolic blood pressure during SCT in the SCB group and the control group were significantly lower than the baseline values (P < 0.05). However, the decrease in the SCB group (70-73bpm VS 108-115 mmHg) was milder than that of the control groupï¼66-72 bpm VS 105-114 mmHgï¼(P < 0.05). The number of surgeries and medication pauses due to symptomatic reflex bradycardia during surgery was significantly lower in the SCB group (2 VS 1) than in the control group (9 VS 7) (P < 0.05). Conclusion: SCB can effectively reduce the vagal reflex caused by pulling the spermatic cord during MSV, and reduce the risk of anesthesia and surgery.
RESUMEN
BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.
Asunto(s)
Función del Atrio Izquierdo , Cardiomiopatía Hipertrófica , Diabetes Mellitus , Imagen por Resonancia Cinemagnética , Valor Predictivo de las Pruebas , Volumen Sistólico , Función Ventricular Izquierda , Remodelación Ventricular , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cardiomiopatía Hipertrófica/diagnóstico por imagen , Cardiomiopatía Hipertrófica/fisiopatología , Cardiomiopatía Hipertrófica/complicaciones , Estudios Retrospectivos , Anciano , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Diabetes Mellitus/diagnóstico , Factores de Riesgo , Adulto , Pronóstico , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/etiología , Comorbilidad , Remodelación AtrialRESUMEN
BACKGROUND: Patients with concomitant type 2 diabetes mellitus (T2DM) and aortic regurgitation (AR) can present with right ventricular (RV) dysfunction. The current study aimed to evaluate the impact of AR on RV impairment and the importance of ventricular interdependence using cardiac magnetic resonance feature tracking (CMRFT) in patients with T2DM. METHODS: This study included 229 patients with T2DM (AR-), 88 patients with T2DM (AR+), and 122 healthy controls. The biventricular global radial strain (GRS), global circumferential strain (GCS), and global longitudinal peak strain (GLS) were calculated with CMRFT and compared among the healthy control, T2DM (AR-), and T2DM (AR+) groups. The RV regional strains at the basal, mid, and apical cavities between the T2DM (AR+) group and subgroups with different AR degrees were compared. Backward stepwise multivariate linear regression analyses were performed to determine the effects of AR and left ventricular (LV) strains on RV strains. RESULTS: The RV GLS, LV GRS, LV GCS, LV GLS, interventricular septal (IVS) GRS and IVS GCS were decreased gradually from the controls through the T2DM (AR-) group to the T2DM (AR+) group. The IVS GLS of the T2DM (AR-) and T2DM (AR+) groups was lower than that of the control group. AR was independently associated with LV GRS, LV GCS, LV GLS, RV GCS, and RV GLS. If AR and LV GLSs were included in the regression analyses, AR and LV GLS were independently associated with RV GLS. CONCLUSION: AR can exacerbate RV dysfunction in patients with T2DM, which may be associated with the superimposed strain injury of the left ventricle and interventricular septum. The RV longitudinal and circumferential strains are important indicators of cardiac injury in T2DM and AR. The unfavorable LV-RV interdependence supports that while focusing on improving LV function, RV dysfunction should be monitored and treated in order to slow the progression of the disease and the onset of adverse outcomes.