Left bundle branch pacing in third-degree atrioventricular block following morrow surgery: a case report

Left bundle branch pacing (LBBP) has proven to be an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle (LV), especially in patients with atrioventricular block and left bundle branch block (LBBB). However, it is unclear whether it still achieved in patients whose left bundle branch (LBB) has had surgery-induced damage. The Morrow operation (Morrow septal myectomy) is regarded as one of the most effective treatments for hypertrophic obstructive cardiomyopathy (HOCM). The surgery resects small sections of muscle tissue in the proximal ventricular septum nearby or contains the LBB, which means that physical damage to the LBB is almost inevitable. Approximately 2%–12% of patients may need pacemaker implanted after Morrow surgery. LBBP is a feasible and effective method for achieving electric resynchronization of LBBB compared to right ventricular pacing (RVB). Nevertheless, there is a dearth of data on LBBP in third-degree atrioventricular block (AVB) following Morrow surgery. We report a case of successful LBBP in those patients

The Effect of Chinese Herbal Medicine on Albuminuria Levels in Patients with Diabetic Nephropathy: A Systematic Review and Meta-Analysis

To evaluate the effect of Chinese herbal medicine (CHM) on albuminuria levels in patients with diabetic nephropathy (DN), we performed comprehensive searches on Medline database, Cochrane Library, CNKI database, CBM database, Wanfang database, and VIP database up to December 2012. A total of 29 trials including 2440 participants with DN met the selection criteria. CHM was tested to be more effective in reducing urinary albumin excretion rate (UAER) (MD −82.95 μg/min, [−138.64, −27.26]) and proteinuria (MD −565.99 mg/24 h, [−892.41, −239.57]) compared with placebo. CHM had a greater beneficial effect on reduction of UAER (MD −13.41 μg/min, [−20.63, −6.19]) and proteinuria (MD −87.48 mg/24 h, [−142.90, −32.06]) compared with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). Combination therapy with CHM and ACEI/ARB showed significant improvement in UAER (MD −28.18 μg/min, [−44.4, −11.97]), urinary albumin-creatinine ratio (MD −347.00, [−410.61, −283.39]), protein-creatinine ratio (MD −2.49, [−4.02, −0.96]), and proteinuria (MD −26.60 mg/24 h, [−26.73, −26.47]) compared with ACEI/ARB alone. No serious adverse events were reported. CHM seems to be an effective and safe therapy option to treat proteinuric patients with DN, suggesting that further study of CHM in the treatment of DN is warranted in rigorously designed, multicentre, large-scale trials with higher quality worldwide

A high-accuracy, low-cost blood test for Alzheimer’s disease: validating P-tau181/Aβ42 in real-world cohorts

ObjectiveTo evaluate the diagnostic performance of plasma P-tau181/Aβ42 measured via flow cytometry as a cost-effective tool for Alzheimer’s disease (AD) diagnosis.MethodsA cohort study involved 123 healthy controls, 60 AD/mild cognitive impairment (MCI) patients, 34 subcortical ischemic vascular disease (SIVD) patients, and 34 frontotemporal dementia (FTD) patients. Plasma P-tau181 and Aβ42 levels were measured using flow cytometry and cross-validated with Single-molecule Array (SIMOA). Publicly available Chinese cohort data were reanalyzed for comparative performance.ResultsThe P-tau181/Aβ42 ratio revealed significant differences between groups. A reference interval (0–0.109) achieved 96.2% diagnostic accuracy (95.0% sensitivity, 96.7% specificity) for AD versus controls, distinguishing AD from SIVD (88.3% accuracy) and FTD (86.2% accuracy). Flow cytometry-based P-tau181/Aβ42 showed 88.3% consistency with SIMOA-based P-tau217, while SIMOA-based P-tau181/Aβ42 achieved 92.3% accuracy.ConclusionFlow cytometry-based P-tau181/Aβ42 offers a cost-effective and accurate diagnostic method for AD, with performance comparable to SIMOA. This biomarker supports scalable AD screening in secondary healthcare settings, overcoming accessibility and cost barriers in resource-limited environments. This biomarker supports scalable AD screening in secondary healthcare settings, overcoming accessibility and cost barriers in resource-limited environments

TRH Analog, Taltirelin Protects Dopaminergic Neurons From Neurotoxicity of MPTP and Rotenone

Dopaminergic neurons loss is one of the main pathological characters of Parkinson’s disease (PD), while no suitable neuroprotective agents have been in clinical use. Thyrotropin-releasing hormone (TRH) and its analogs protect neurons from ischemia and various cytotoxins, but whether the effect also applies in PD models remain unclear. Here, we showed that Taltirelin, a long-acting TRH analog, exhibited the neuroprotective effect in both cellular and animal models of PD. The in vitro study demonstrated that Taltirelin (5 μM) reduced the generation of reactive oxygen species (ROS) induced by MPP+ or rotenone, alleviated apoptosis and rescued the viability of SH-SY5Y cells and rat primary midbrain neurons. Interestingly, SH-SY5Y cells treated with Taltirelin also displayed lower level of p-tau (S396) and asparagine endopeptidase (AEP) cleavage products, tau N368 and α-synuclein N103 fragments, accompanied by a lower intracellular monoamine oxidase-B (MAO-B) activity. In the subacute MPTP-induced and chronic rotenone-induced PD mice models, we found Taltirelin (1 mg/kg) significantly improved the locomotor function and preserved dopaminergic neurons in the substantia nigra (SN). In accordance with the in vitro study, Taltirelin down-regulated the levels of p-tau (S396), p-α-synuclein (S129) tau N368 and α-synuclein N103 fragments in SN and striatum. Together, this study demonstrates that Taltirelin may exert neuroprotective effect via inhibiting MAO-B and reducing the oxidative stress and apoptosis, preventing AEP activation and its subsequent pathological cleavage of tau and α-synuclein, thus provides evidence for Taltirelin in protective treatment of PD

TRH Analog, Taltirelin Improves Motor Function of Hemi-PD Rats Without Inducing Dyskinesia via Sustained Dopamine Stimulating Effect

Thyrotropin-releasing hormone (TRH) and its analogs are able to stimulate the release of the endogenic dopamine (DA) in the central nervous system. However, this effect has not been tested in the Parkinson’s disease (PD), which is characterized by the DA deficiency due to the dopaminergic neurons loss in the substantia nigra. Here, we investigated the therapeutic effect of Taltirelin, a long-acting TRH analog on 6-hydroxydopamine-lesioned hemi-Parkinsonian rat model. 1–10 mg/kg Taltirelin i.p. administration significantly improved the locomotor function and halted the electrophysiological abnormities of PD animals without inducing dyskinesia even with high-dose for 7 days treatment. Microdialysis showed that Taltirelin gently and persistently promoted DA release in the cortex and striatum, while L-DOPA induced a sharp rise of DA especially in the cortex. The DA-releasing effect of Taltirelin was alleviated by reserpine, vanoxerine (GBR12909) or AMPT, indicating a mechanism involving vesicular monoamine transporter-2 (VMAT-2), dopamine transporter (DAT) and tyrosine hydroxylase (TH). The in vivo and in vitro experiments further supported that Taltirelin affected the regulation of TH expression in striatal neurons, which was mediated by p-ERK1/2. Together, this study demonstrated that Taltirelin improved motor function of hemi-PD rats without inducing dyskinesia, thus supporting a further exploration of Taltirelin for PD treatment

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma

ObjectiveUterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM.Methods124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA).ResultsClinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046).ConclusionThis study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment

Delta-secretase triggers Alzheimer’s disease pathologies in wild-type hAPP/hMAPT double transgenic mice

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease with multifactorial pathologies including Aβ containing senile plaques and neurofibrillary tangles (NFT) consisted of aggregated Tau. Most of the AD patients are sporadic and the familial mutation hereditary patients are composed only 1% of all cases. However, the current AD mouse models employ mutated APP, PS1, or even Tau mutant, in order to display a portion of AD pathologies. Delta-secretase (legumain, or asparaginyl endopeptidase, AEP) simultaneously cleaves both APP and Tau and augments Aβ production and Tau hyperphosphorylation and aggregation, contributing to AD pathogenesis. Here we show that δ-secretase is sufficient to promote prominent AD pathologies in wild-type hAPP/hMAPT double transgenic mice. We crossed hAPP l5 mice and hMAPT mice to generate double transgenic mouse model carrying both human wild-type APP and Tau. Compared to the single transgenic parents, these double transgenic mice demonstrated AD-related pathologies in one-year-old hAPP/hMAPT mice. Notably, overexpression of δ-secretase in hAPP/hMAPT double-transgenic mice evidently accelerated enormous senile plaques and NFT, associated with prominent synaptic defects and cognitive deficits. Hence, δ-secretase facilitates AD pathogenesis independent of any patient-derived mutation.</jats:p

Vertical Distribution, Diurnal Evolution, and Source Region of Formaldehyde During the Warm Season Under Ozone-Polluted and Non-Polluted Conditions in Nanjing, China

Formaldehyde (HCHO), a key volatile organic compound (VOC) in the atmosphere, plays a crucial role in driving photochemical processes. Satellite-based observations of column concentrations of HCHO and other gaseous pollutants (e.g., NO2) have generally been used in previous studies to elucidate the mechanisms behind secondary organic aerosol (SOA) and ozone (O3) formation. This study aimed to investigate the characteristics of HCHO by retrieving its vertical profile over Nanjing during the warm season (May&ndash;June 2022) and analyzing the diurnal variation in vertical distribution and potential source regions on non-polluted (MDA8 O3 &lt; 160 &mu;g m&minus;3, NO3P) and O3-polluted (MDA8 O3 &ge; 160 &mu;g m&minus;3, O3P) days. Under both conditions, HCHO was primarily concentrated below 1.5 km altitude, with average vertical profiles displaying similar Boltzmann-like distributions. However, HCHO concentrations on O3P days were 1.2&ndash;1.6 times higher than those on non-polluted days at the same altitude below 1.5 km. Maximum HCHO concentrations occurred in the afternoon, while the peak value in the 0.1&ndash;0.4 km layers was reached around noon (~11:00 a.m.). The variation rates (VR) of HCHO in the 0.3&ndash;1.2 km altitudes had a maximum on O3P days (approximately 0.33 ppbv h&minus;1), and were significantly higher (p &lt; 0.01) than the VR observed on NO3P days (0.14&ndash;0.20 ppbv h&minus;1). The analysis of footprints showed that HCHO concentrations were jointly influenced by the upstream region and the surroundings of the study site. The study results improve the understanding of the vertical distribution and potential source regions of HCHO