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Group 2 innate lymphocytes (ILC2) have an important role in orchestrating sepsis-induced immune response. However, the impact of LC2 on sepsis-induced cardiac injury is still not fully understood. This study investigated the mechanisms governing ILC2 activation within the cardiac tissue after sepsis. In vivo experiments using wild-type and IL-33 deficient mice indicated that the presence of interleukin (IL)-33, which participates in expanding and activating ILC2 cells, was correlated with higher ILC2 levels (246 ± 34 vs. 66 ± 18, p  < 0.01), reduced cardiac dysfunction, and lower markers of cardiac injury. Conversely, IL-33 deficiency led to exacerbated cardiac damage. Additionally, heart ILC2 significantly increased the expression and secretion of IL-5 (2.18 ± 0.34 ng/ml vs. 1.18 ± 0.24 ng/ml, p  < 0.05) and IL-13 (10.55 ± 1.13 ng/ml vs. 7.59 ± 1.13 ng/ml, p  < 0.05) following sepsis, with this response being mediated by IL-33. Moreover, IL-5 deficient mice exhibited increased cardiac dysfunction and myocardial apoptosis post-sepsis (20.7 ± 4.28% vs. 29.61 ± 4.28%, p  < 0.05). Furthermore, in vitro experiments involving co-cultures of ILC2 with mice cardiomyocytes after lipopolysaccharide (LPS) administration suggested that IL-5 derived from ILC2 protects cardiomyocytes from autophagy and apoptosis. These findings imply that IL-33, released in response to sepsis, induces ILC2 activation and IL-5 secretion, orchestrating the equilibrium between autophagy and apoptosis in cardiomyocytes and offering potential therapeutic avenues for mitigating sepsis-induced cardiac injury.

Background The heterogeneity of sepsis poses challenges for the individualized treatment of vasoactive drugs. Methods This study used data from ICUs in MIMIC-IV (2008–2019) and eICU (2014–2015) databases, identified sepsis by sepsis-3 criteria, and stratified sepsis into phenotypes by consensus K-means. The norepinephrine equivalence (NEE) formula balance treatment of different vasoactive drugs, with NEE captured hourly for up to 72 h to record both time of use and dosage. The logistic regression model, including phenotype–dosage–time interactions, examined heterogeneous treatment effects on hospital mortality. To address confounding, three models were fitted: Model 1 unadjusted, Model 2 adjusted for age and sex, and Model 3 additionally included 7 clinical variables identified via machine learning and directed acyclic graph. Nonlinear dosage was further analyzed based on restricted cubic splines. P values and P for interaction were Bonferroni-adjusted. Results A total of 54,673 sepsis patients were included for phenotype identification, and 8,803 patients were further analyzed to evaluate heterogeneous treatment effect of vasoactive drugs. Four sepsis phenotypes were identified: A, B, C and D. Phenotype D was the most severe subgroup, followed by phenotype C, while phenotypes A and B were mild subgroups. In Model 3, each 0.05 μg/kg/min increase in NEE dosage was linked to higher hospital mortality (OR 1.328, 95% CI 1.314–1.342; p  < 0.001). Longer NEE time of use also significantly increased mortality risk (OR 1.006, 95% CI 1.005–1.007; p  < 0.001). In addition, these associations varied significantly by phenotype ( P for interaction < 0.001). In RCS model, phenotype A consistently showed higher mortality than the other phenotypes at NEE dosages of 0.1–0.5 µg/kg/min, with this gap increasing over time, showing a clear dosage–time dependence. Phenotype B displayed lower overall mortality but the steepest relative risk of hospital mortality increased as dosage and time (OR of dosage: 1.309; OR of time: 1.005) in Model 3. Phenotype C reached the highest mortality risk when dosages exceeded 0.5 µg/kg/min, which was dosage dependence. Finally, phenotype D followed a U-shaped curve in RCS model, and minimum mortality was around 20% at 0.03–0.05 µg/kg/min. Conclusions Sepsis phenotypes differ significantly in their treatment effects of vasoactive drug dosage and time of use, indicating the need for phenotype-specific treatment strategies to improve outcomes.

Objective To compare the clinical outcomes of limited open reduction versus closed reduction in retrograde intramedullary nailing for mid-distal femoral shaft fractures. Methods A retrospective analysis was conducted on 107 patients with isolated mid-distal femoral shaft fractures treated with retrograde intramedullary nailing between January 2016 and May 2024. Patients were divided into two groups: limited open reduction (61 cases) and closed reduction (46 cases). The two groups were compared in terms of the number of intraoperative fluoroscopies, operative time, intraoperative blood loss, the number of cases requiring open reduction due to failed reduction, postoperative VAS scores, and/or incision-related complications. During a follow-up period of 9–36 months, HSS functional scores and postoperative nonunion rates were evaluated to assess efficacy. Results The limited open reduction group showed statistically significant advantages over the closed reduction group in the following metrics: the number of intraoperative fluoroscopies (9.33 vs. 12.24 times, p  = 0.001), operative time (92.61 vs. 108.65 min, p  = 0.018), intraoperative blood loss (209.18 vs. 237.83 mL, p  = 0.001), the number of cases requiring open reduction (5 vs. 12 cases, p  = 0.012), and postoperative nonunion rate (2 vs. 5 cases, p  = 0.034). No statistically significant differences were observed between the two groups in early incision-related complications (3 vs. 6 cases, p  = 0.772), postoperative VAS scores (3.44 vs. 3.55, p  = 0.820), or HSS knee function scores 6 months postoperatively (92.72 vs. 92.31, p  = 0.674). Conclusion Compared with closed reduction, limited open reduction at the fracture plane in retrograde intramedullary nailing for mid-distal femoral shaft fractures offers significant advantages: it facilitates rapid insertion of the long guidewire, reduces the number of fluoroscopies, shortens operative time, decreases intraoperative blood loss, and minimizes intraoperative changes in the surgical strategy. Importantly, the limited open reduction does not increase incision-related complications or pain and does not affect knee joint function.

The role of miR-26a-5p expression in cardiac hypertrophy remains unclear. Herein, the effect of miR-26a-5p on cardiac hypertrophy was investigated using phenylephrine (PE)-induced cardiac hypertrophy in vitro and in a rat model of hypertension-induced hypertrophy in vivo. The PE-induced cardiac hypertrophy models in vitro and vivo were established. To investigate the effect of miR-26a-5p activation on autophagy, the protein expression of autophagosome marker (LC3) and p62 was detected by western blot analysis. To explore the effect of miR-26a-5p activation on cardiac hypertrophy, the relative mRNA expression of cardiac hypertrophy related mark GSK3 was detected by qRT-PCR in vitro and vivo. In addition, immunofluorescence staining was used to detect cardiac hypertrophy related mark -actinin. The cell surface area was measured by immunofluorescence staining. The direct target relationship between miR-26a-5p and GSK3 was confirmed by dual luciferase report. MiR-26a-5p was highly expressed in PE-induced cardiac hypertrophy. MiR-26a-5p promoted LC3II and decreased p62 expression in PE-induced cardiac hypertrophy in the presence or absence of lysosomal inhibitor. Furthermore, miR-26a-5p significantly inhibited GSK3 expression in vitro and in vivo. Dual luciferase report results confirmed that miR-26a-5p could directly target GSK3 . GSK3 overexpression significantly reversed the expression of cardiac hypertrophy-related markers including ANP, ACTA1 and MYH7. Immunofluorescence staining results demonstrated that miR-26a-5p promoted cardiac hypertrophy related protein -actinin expression, and increased cell surface area in vitro and in vivo. Our study revealed that miR-26a-5p promotes myocardial cell autophagy activation and cardiac hypertrophy by regulating GSK3 , which needs further research.

Background Conventional prenatal screening tests, such as maternal serum tests and ultrasound scan, have limited resolution and accuracy. Methods We developed an advanced noninvasive prenatal diagnosis method based on massively parallel sequencing. The Noninvasive Fetal Trisomy (NIFTY) test, combines an optimized Student’s t-test with a locally weighted polynomial regression and binary hypotheses. We applied the NIFTY test to 903 pregnancies and compared the diagnostic results with those of full karyotyping. Results 16 of 16 trisomy 21, 12 of 12 trisomy 18, two of two trisomy 13, three of four 45, X, one of one XYY and two of two XXY abnormalities were correctly identified. But one false positive case of trisomy 18 and one false negative case of 45, X were observed. The test performed with 100% sensitivity and 99.9% specificity for autosomal aneuploidies and 85.7% sensitivity and 99.9% specificity for sex chromosomal aneuploidies. Compared with three previously reported z-score approaches with/without GC-bias removal and with internal control, the NIFTY test was more accurate and robust for the detection of both autosomal and sex chromosomal aneuploidies in fetuses. Conclusion Our study demonstrates a powerful and reliable methodology for noninvasive prenatal diagnosis.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all‐cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24‐h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24‐h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long‐acting antihypertensive medications are preferred for nocturnal and 24‐h BP control. Some newly developed agents, renal denervation, and other device‐based therapy on nocturnal BP reduction are evaluated.

Background. Obstructive sleep apnea (OSA) is common in patients with hypertension. Nonetheless, OSA is underdiagnosed despite considerable evidence of the association between OSA and adverse health outcomes. This study developed and validated a clinical nomogram to predict OSA in patients with hypertension based on the Epworth Sleepiness Scale (ESS) score and OSA-related parameters. Methods. A total of 347 hypertensive patients with suspected OSA were retrospectively enrolled and randomly assigned to a training set and a validation set at 70 : 30 (N = 242/N = 105) ratio. OSA was diagnosed through sleep monitoring and was defined as an apnea-hypopnea index ≥5 events/h. Using the least absolute shrinkage and selection operator regression model, we identified potential predictors of OSA and constructed a nomogram model in the training set. The predictive performance of the nomogram was assessed and validated by discrimination and calibration. The nomogram was also compared with ESS scores according to decision curve analysis (DCA), integrated discrimination index (IDI), and net reclassification index (NRI). Results. ESS scores, body mass index, neck circumference, snoring, and observed apnea predicted OSA are considered. The nomogram showed similar discrimination between the training set (AUC: 0.799, 95% CI: 0.743–0.847) and validation set (AUC: 0.766, 95% CI: 0.673–0.843) and good calibration in the training (P=0.925>0.05) and validation (P=0.906>0.05) sets. Compared with the predictive value of the ESS, the nomogram was clinically useful and significantly improved reclassification accuracy (NRI: 0.552, 95% CI: 0.282–0.822, P<0.001; IDI: 0.088, 95% CI: 0.045–0.133, P<0.001) at a probability threshold of >42%. Conclusions. We developed a novel OSA prediction nomogram based on ESS scores and OSA-related parameters. This nomogram may help improve clinical decision-making, especially in communities and primary clinics, where polysomnography is unavailable.

There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients’ and physicians’ satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug‐related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM‐AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

PurposeAntihypertensive treatment is the most important method to reduce the risk of cardiovascular events in hypertensive patients. However, there is scant evidence of the benefits of levoamlodipine maleate for antihypertensive treatment using a head-to-head comparison in the real-world. This study aims to examine the effectiveness of levoamlodipine maleate used to treat outpatients with primary hypertension compared with amlodipine besylate in a real-world setting.MethodsThis was a pragmatic comparative effectiveness study carried out at 110 centers across China in outpatients with primary hypertension treated with levoamlodipine maleate or amlodipine besylate, with 24 months of follow-up. The primary outcomes used for evaluating the effectiveness were composite major cardiovascular and cerebrovascular events (MACCE), adverse reactions, and cost-effectiveness.ResultsAmong the included 10,031 patients, there were 482 MACCE, 223 (4.4%) in the levoamlodipine maleate group (n = 5018) and 259 (5.2%) in the amlodipine besylate group (n = 5013) (adjusted hazard ratio = 0.90, 95%CI: 0.75-1.08, P = 0.252). The levoamlodipine maleate group had lower overall incidences of any adverse reactions (6.0% vs. 8.4%, P < 0.001), lower extremity edema (1.1% vs. 3.0%, P < 0.001) and headache (0.7% vs. 1.1%, P = 0.045). There was a nearly 100% chance of the levoamlodipine maleate being cost-effective at a willingness to pay threshold of 150,000 Yuan per quality-adjusted life years (QALYs) gained, resulting in more QALYs (incremental QALYs: 0.00392) and cost savings (saving 2725 Yuan or 28.8% reduction in overall costs) per patient.ConclusionIn conclusion, levoamlodipine maleate could reduce cost by 29% with a similar MACCE incidence rate and lower occurrence of adverse reactions (especially edema and headache) compared with amlodipine besylate.Trial RegistrationClinicaltrials.gov NCT01844570 registered at May 1, 2013.

Beta thalassemia is a hereditary disorder resulted from mutations in the β globin gene leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. Three types have been defined, based on the degree of reduced beta-globin chain synthesis and clinical phenotype: major, intermedia and minor (heterozygote carrier state). Beta thalassemia intermedia is characterized by heterogeneity for the wide clinical spectrum of various genotypes and a wide range of presentations. The genotypes of beta thalassemia intermedia are much complicated referring to β+/β+,β+/β0, Hb E/β0, β0/β0 compounding alpha thalassemia and so on. In this present case, we reported a rare beta thalassemia intermedia genotype of double heterozygosity for poly A (A>G) and CD17(A>T) indicated of β+/β0 in a Chinese family.