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Objectives The aims of the study were to assess the management of low-density lipoprotein cholesterol (LDL-C) and the goal achievement, as well as to investigate the association between baseline LDL-C level, lipid-lowering treatment (LLT), and stroke recurrence in patients with ischaemic stroke or transient ischaemic attack (TIA).Design Our study was a post hoc analysis of the Third China National Stroke Registry (CNSR-III).Setting We derived data from the CNSR-III - a nationwide clinical registry of ischaemic stroke and TIA based on 201 participating hospitals in mainland China.Participants 15,166 patients were included in this study with demographic characteristics, etiology, imaging, and biological markers from August 2015 to March 2018.Primary and secondary outcome measures The primary outcome was a new stroke, LDL-C goal (LDL-C

Background Small single subcortical infarction (SSSI) may be classified as parent artery disease-related or only branch involved according to the stenosis of parent artery. The study aimed to evaluate short-term and long-term prognoses and the effectiveness of antiplatelet therapy in SSSI.Methods We prospectively enrolled 2890 patients with SSSI from the Third China National Stroke Registry (CNSR-III) database from August 2015 to March 2018. We assessed clinical outcomes and antiplatelet treatment effects in patients with SSSI with and without parent artery stenosis (PAS) identified by magnetic resonance angiography.Results Among 2890 patients with SSSI in the perforator territory of the middle cerebral artery and the basilar artery, there were 680 (23.53%) patients with PAS and 2210 (76.47%) patients without PAS, respectively. After adjusting for potential confounders, the PAS group had a greater initial stroke severity (OR 1.262, 95% CI 1.058 to 1.505; p=0.0097) and a higher risk of ischaemic stroke recurrence at 3 months (OR 2.266, 95% CI 1.631 to 3.149; p

This study presents a miniaturized head-mount optical coherence tomography (OCT) system tailored for high-resolution brain imaging in freely moving mice, providing an advanced noninvasive imaging tool in neuroscience research. Leveraging optical coherence tomography technology, the system enables depth-resolved imaging and integrates functional OCT extensions, including angiography and Doppler imaging. Remarkably lightweight at 1.5 g, the device allows for the preservation of natural mouse behavior during imaging sessions. With a maximum 4 × 4 mm field of view and 7.4 μm axial resolution, the system offers reliable imaging capabilities. Noteworthy features include focal adjustability, rotary joint integration for fiber-twist-free operation, and a high-speed swept-source OCT laser at 200 kHz, facilitating real-time imaging. By providing insights into brain mechanisms and neurological disorders without disrupting natural behavior, this innovative system holds promise as a powerful tool in neuroscience research. Its compact design and comprehensive imaging capabilities make it well-suited for studying various brain regions and dynamic processes, contributing significantly to our understanding of brain function and pathology.

Background: Effective drug delivery of nanomedicines to targeted sites remains challenging. Given that hypobaric hypoxia and hyperbaric oxygen exposure can significantly change pharmacokinetics of drugs, it is interesting to determine whether they can regulate tissue distribution of nanomedicine, especially in tumor, for enhanced cancer therapy. Results: Hypobaric hypoxia exposure improved the pharmacokinetics of paclitaxel-loaded liposomes and facilitated their distribution in the heart and liver, whereas hyperbaric oxygen exposure did not benefit and even impaired the pharmacokinetics and distribution. Particularly, both hypobaric hypoxia and hyperbaric oxygen exposure could not improve the distribution in subcutaneous tumor. Thus, we constructed orthotopic liver tumor model and discussed whether high distribution of the liposomal nanomedicine in the liver, facilitated by hypobaric hypoxia exposure, could ensure their effective accumulation in liver tumor for enhanced cancer therapy. Conclusions: The liposomal nanomedicine with adjuvant hypobaric hypoxia exposure significantly inhibited the growth of orthotopic liver tumor for prolonged survival time, achieved by hypobaric hypoxia-promoted accumulation at tumor sites of the liver. It might be the first example of the application of adjuvant intermittent hypobaric hypoxia exposure in treating liver cancer.

BackgroundThe Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiological changes that may lead to hypotension. The original validation used a case control (backwards) analysis that has been suggested to be biased. We therefore conducted a cohort (forwards) analysis and compared this to the original validation technique.MethodsWe conducted a retrospective analysis of data from previously reported studies. All data were analysed identically with 2 different methodologies and receiver operating characteristic curves (ROC) constructed. Both backwards and forwards analyses were performed to examine differences in area under the ROC for HPI and other haemodynamic variables to predict a MAP < 65mmHg for at least 1 minute 5, 10 and 15 minutes in advance.ResultsTwo thousand and twenty-two patients were included in the analysis, yielding 4,152,124 measurements taken at 20 second intervals. The area-under-the-curve for the index predicting hypotension analysed by backward and forward methodologies respectively was 0.957 (95% CI, 0.947-0.964) vs 0.923 (95% CI, 0.912-0.933) 5 minutes in advance, 0.933 (95% CI, 0.924-0.942) vs 0.923 (95% CI, 0.911-0.933) 10 minutes in advance , and 0.929 (95% CI, 0.918-0.938) vs. 0.926 (95% CI, 0.914-0.937) 15 minutes in advance. No other variable had an area-under-the-curve > 0.7 except for MAP. Area-under-the-curve using forward analysis for MAP predicting hypotension 5, 10, and 15 minutes in advance was 0.932 (95% CI, 0.920-0.940), 0.929 (95% CI, 0.918-0.938), and 0.932 (95% CI, 0.921-0.940). The R 2 for the variation in the index due to MAP was 0.77.ConclusionUsing an updated methodology, we found the utility of the HPI index to predict future hypotensive events is high, with an area under the receiver-operating-characteristics curve similar to that of the original validation method.

Abstract Background Sex differences in outcomes after small artery occlusion (SAO) stroke have not been well described, particularly in a Chinese population. We aimed to assess sex differences in outcomes and related risk factors among patients with SAO. Methods All consecutive patients with SAO were recruited between May 2005 and September 2014. Clinical features and risk factors were recorded. The mortality, recurrence, and dependency rates at 3 months after stroke were assessed. Results A total of 2524 patients with SAO were included in this study. There was a higher frequency of mild stroke, current smoking, and alcohol consumption in men than in women. Women were more likely than men to be older, to have diabetes and obesity, and to have higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels. There were worse outcomes in men than in women at 3 months after stroke (P

Photo-mediated ultrasound therapy (PUT) is a novel antivascular therapeutic modality based on cavitation-induced bioeffects. During PUT, synergistic combinations of laser pulses and ultrasound bursts are used to remove the targeted microvessels selectively and precisely without harming nearby tissue. In the current study, an integrated system combining PUT and spectral domain optical coherence tomography (SD-OCT) was developed, where the SD-OCT system was used to guide PUT by detecting cavitation in real time in the retina of the eye.MethodWe first examined the capability of SD-OCT in detecting cavitation on a vascular-mimicking phantom and compared the results with those from a passive cavitation detector. The performance of the integrated system in treatment of choroidal microvessels was then evaluated in rabbit eyes in vivo.ResultsDuring the in vivo PUT experiments, several biomarkers at the subretinal layer in the rabbit eye were identified on OCT images. The findings indicate that, by evaluating biomarkers of treatment effect, real-time SD-OCT monitoring could help to avoid micro-hemorrhage, which is a potential major side effect.ConclusionReal-time OCT monitoring can thus improve the safety and efficiency of PUT in removing the retinal and choroidal microvasculature.

ObjectiveDrug induced sleep endoscopy (DISE) is often performed for pediatric obstructive sleep apnea (OSA) when initial diagnostic studies do not provide adequate information for therapy. However, DISE scoring is subjective and with limitations. This proof-of-concept study demonstrates the use of a novel long-range optical coherence tomography (LR-OCT) system during DISE of two pediatric patients.MethodsLR-OCT was used to visualize the airway of pediatric patients during DISE. At the conclusion of DISE, the OCT probe was guided in the airway under endoscopic visual guidance, and cross-sectional images were acquired at the four VOTE locations. Data processing involved image resizing and alignment, followed by rendering of three-dimensional (3D) volumetric models of the airways.ResultsTwo patients were included in this study. Patient one had 18.4%, 20.9%, 72.3%, and 97.3% maximal obstruction at velum, oropharynx, tongue base, and epiglottis, while patient two had 40.2%, 41.4%, 8.0%, and 17.5% maximal obstruction at these regions, respectively. Three-dimensional reconstructions of patients' airways were also constructed from the OCT images.ConclusionThis proof-of-concept study demonstrates the successful evaluation of pediatric airway during DISE using LR-OCT, which accurately identified sites and degrees of obstruction with respective 3D airway reconstruction.

Abstract Intracerebral hemorrhage (ICH) is common in China. However, the sex differences in clinical features, risk factors, and outcomes of ICH remain controversial. Between 2005 and 2014, we recruited patients with primary ICH in Tianjin, China, and evaluated sex differences in clinical features, risk factors, and outcomes at 3, 12, and 36 months after ICH. The 1,325 patients included 897 men (67.7%) and 428 women (32.3%). The mean age at ICH onset was younger among men (59.14 years) than among women (63.12 years, P

Fractional-pixel CO2 laser therapy shows promise for treating the genitourinary syndrome of menopause (GSM). Nevertheless, it remains controversial in the field of female pelvic medicine. This is due to the inherent difficulties in obtaining noninvasive biopsies to evaluate the treatments efficacy and safety objectively. To address this challenge, we developed a noninvasive intravaginal optical coherence tomography (OCT)/OCT angiography (OCTA) endoscopic system, whose probe features a shape identical to the laser treatment probe. This system can provide high-resolution OCT images to identify the microstructure of vaginal tissue and visualize the vasculature network in vivo. We conducted clinical research on 25 post-menopausal patients with GSM. OCT/OCTA scans were acquired at four different locations of the vagina (distal anterior, distal posterior, proximal anterior, and proximal posterior) during the whole laser treatment session. A U-Net deep learning model was applied to segment the vaginal epithelium for assessing vaginal epithelial thickness (VET). Blood vessel density and VET were quantified to monitor the efficacy of fractional-pixel CO2 laser therapy. Statistical correlation analyses between these metrics and other clinical scores were conducted, validating the utility of our system. This OCT/OCTA endoscopic system has great potential to serve as a noninvasive biopsy tool in gynecological studies to screen, evaluate, and guide laser treatment for GSM.

Highlights 1. A class of solvent-free covalent organic framework (COF) single-ion conductors (Li-COF@P) has been designed via ion–dipole interaction as opposed to traditional ion–ion interaction, promoting ion dissociation and Li+ migration through directional ionic channels. 2. The Li-COF@P enabled long cycle life (88.3% after 2000 cycles) in all-solid-state Li organic batteries (ASSLOBs) under ambient operating conditions, which outperformed those of previously reported ASSOLBs. 3. This Li-COF@P strategy holds promise as a viable alternative to the currently prevalent inorganic solid electrolytes.

Objective(s): Slit guidance ligand 3 (SLIT3) has been identified as a potential therapeutic regulator against fibroblast activity and fibrillary collagen production in an autocrine manner. However, this research aims to investigate the potential role of SLIT3 in cardiac fibrosis and fibroblast differentiation and its underlying mechanism.Materials and Methods: C57BL/6 mice (male, 8-10 weeks, n=47) were subcutaneously infused with Ang II (2.0 mg/kg/day) for 4 weeks. One to two-day-old Sprague-Dawley (SD) rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (60 mg/kg) and ketamine (50 mg/kg) and the cardiac fibroblast was isolated aseptically. The mRNA and protein expression were analyzed using RT-qPCR and Western blotting.Results: The SLIT3 expression level was increased in Ang II-induced mice models and cardiac fibroblasts. SLIT3 significantly increased migrated cells and α-smooth muscle actin (α-SMA) expression in cardiac fibroblasts. Ang II-induced increases in mRNA expression of collagen I (COL1A1), and collagen III (COL3A1) was attenuated by SLIT3 inhibition. SLIT3 knockdown attenuated the Ang II-induced increase in mRNA expression of ACTA2 (α-SMA), Fibronectin, and CTGF. SLIT3 suppression potentially reduced DHE expression and decreased malondialdehyde (MDA) content, and the superoxide dismutase (SOD) and catalase (CAT) levels were significantly increased in cardiac fibroblasts. Additionally, SLIT3 inhibition markedly decreased RhoA and ROCK1 protein expression, whereas ROCK inhibitor Y-27632 (10 μM) markedly attenuated the migration of cardiac fibroblasts stimulated by Ang II and SLIT3.Conclusion: The results speculate that SLIT3 could significantly regulate cardiac fibrosis and fibroblast differentiation via the RhoA/ROCK1 signaling pathway.

ObjectiveOptical coherence elastography (OCE) was used to demonstrate the relationship between the elasticity of the optic nerve head (ONH) and different intraocular pressure (IOP) levels in an in-vivo rabbit model for the first time.MethodBoth ex-vivo and in-vivo rabbit ONH were imaged using OCE system. A mechanical shaker initiated the propagation of elastic waves, and the elasticity of the ONH was determined by tracking the wave propagation speed. The elasticity of the ONH under varying IOP levels was reconstructed based on the wave speed. Notably, the ONH exhibited increased stiffness with elevated IOP.ResultsIn the in-vivo rabbit models, the Young's modulus of ONH increased from 14 kPa to 81 kPa with the IOP increased from 15 mmHg to 35 mmHg. This revealed a positive correlation between the Young's modulus of the ONH and intraocular pressure.ConclusionThe OCE system proved effective in measuring the mechanical properties of ONH at different IOP levels, with validation in an in-vivo rabbit model.SignificanceConsidering ONH plays a critical role in vision and eye diseases, the capability to image and quantify in vivo ONH biomechanical properties has great potential to advance vision science research and improve the clinical management of glaucoma patients.

Clinical treatment of TNBC remains challenging, due to the lack of targeted therapies. As TNBC is highly hypoxic with higher HIF-1α expression than other subtypes, we fabricated hypoxia-responsive polymeric micelles co-loading drug and shRNA to treat TNBC by targeting hypoxic tumor microenvironment and subsequently targeting overexpressed HIF-1α under hypoxia. The micelles were assembled from methoxy-polyethylene glycol (mPEG) and poly-L-lysine (PLL) copolymer with AZO as a hypoxia-responsive bridge of mPEG and PLL. Once exposed to hypoxia, AZO bridge was cleaved, resulting in the disassembly of the micelles for rapid release. In vitro and in vivo results showed that the micelles enabled simultaneous delivery of drug and shRNA to hypoxic sites for site-specific rapid release, facilitated by sensitive response to hypoxia; hypoxia-responsive shRNA delivery effectively silenced HIF-1α and its downstream genes, which not only ameliorated the response of hypoxic tumor to drug, but also modulated tumor microenvironment for further improved drug and shRNA delivery; as a result, synergistic treatment of chemotherapy and HIF-1α targeted gene therapy inhibited the growth of primary TNBC tumor and its distant metastasis in a murine model of orthotopic TNBC. Together with their good biocompatibility, hypoxia-responsive polymeric micelles thus emerged as a safe, effective, and universally applicable drug and gene carrier for treatment of TNBC as well as other hypoxic tumors.

Abstract: Detection of the effects of climate change on ocean ecosystems is often limited by the short duration of available time series. Here, we use ocean transparency measurements (the Secchi disk depth, ZSD) in the California Current Ecosystem since 1949 and combine them with satellite estimates. Historic in situ measurements of ZSD were irregular in space and time and are difficult to interpret in time series due to biases introduced by changing locations and timing. We normalize historic ZSD measurements with satellite‐derived mean climatology and create a merged in situ—satellite time series of ZSD for the last ~ 73 yr. Although interannual variability in ZSD is dominated by El Niño Southern Oscillation‐related variability (~ 50% of the total variance in many areas), a secular trend of decreasing transparency that is correlated with increasing productivity is detected 0–300 km from the coast in an area affected by coastal upwelling north of 27°N. In contrast, increasing transparency (correlated with decreasing productivity) is detected offshore (> 1000 km from the coast). In addition to those general trends, transparency is also increasing in coastal area off Baja California south of 27°N.