Innovative surgical approach for trigeminal trophic syndrome: Successful healing of facial ulcers through cross-face nerve grafts.

BACKGROUND: Trigeminal trophic syndrome (TTS) is a rare condition caused by damage to the trigeminal nervous system, resulting in sensory disturbances and ulcers on the face. Treating TTS is complex and often requires medical or surgical intervention like flap reconstruction. However, there is limited research on surgical treatments for TTS ulcers. METHODS: We report the case of a 19-year-old man with TTS. We employed an innovative surgical technique involving dual cross-face nerve grafts. In the initial procedure, corneal neuralization was accomplished using supraorbital and cross-face infraorbital nerve graft. The subsequent operation utilized auricular composite tissue flap transplantation repair and cross-face mental nerve graft. RESULTS: This procedure led to rapid and sustained healing, as well as aesthetic improvement. CONCLUSION: Cross-face nerve grafts is a promising tool in the treatment of refractory ulcers caused by diseases such as TTS.

Association between baseline office blood pressure level and the incidence and development of long-term frailty in the community-dwelling very elderly with hypertension.

Frailty is the most important risk factor causing disability in the elderly. Hypertension is one of the most common chronic diseases in the elderly and is closely related to frailty, but there is still controversy about the association between blood pressure and frailty. To explore the association between baseline blood pressure level and the incident and development of long-term frailty in the community-dwelling very elderly (i.e., over 80 years old [1]) with hypertension, in order to provide a basis for scientific blood pressure management of very elderly hypertension. In this study, very elderly hypertensive patients who received comprehensive geriatric assessment from January to June 2019 and with complete data were included, and follow-up was conducted from January 1 to February 14, 2023. A total of 330 very elderly individuals with hypertension were enrolled in this study. FRAIL scale was used to evaluate frailty. Binomial logistic regression analysis was used to calculate the OR and 95%CI between baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) levels and long-term incident and development of frailty. The dose-response relationship between baseline office SBP, DBP or PP levels and incident frailty and its development was analyzed by Generalized Additive Model (GAM) using smooth curve fitting and threshold effect analysis. Smooth curve fitting and threshold effect analysis showed that the relationship between baseline office SBP level and incident frailty was U-shaped, with the nadir of the U-shaped curve at 135 mmHg after adjustment. Baseline office SBP, PP level and development frailty was U-shaped and the nadir was 140 mmHg and 77 mmHg. In the community-dwelling very elderly with hypertension, baseline office SBP level had a relationship with long-term incident frailty and its development and PP level had a relationship with long-term development of frailty.

Feasibility of a Mobile Health Intervention for Providing a Continuum of HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in China.

BACKGROUND: Men who have sex with men (MSM) in China have a high risk for HIV infection but experience suboptimal rates of HIV testing and service engagement due to various social and structural barriers. We developed a mobile health (mHealth) intervention entitled "WeTest-Plus" (WeTest+) as a user-centered "one-stop service" approach for delivering access to comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention, confirmatory testing, treatment, and care. OBJECTIVE: The goal of the current study was to investigate the feasibility of WeTest+ to provide continuous HIV services to high-risk MSM. METHODS: Participants completed a 3-week pilot test of WeTest+ to examine acceptability, feasibility, and recommendations for improvement. Participants completed a structured online questionnaire and qualitative exit interviews facilitated by project staff. "Click-through" rates were assessed to examine engagement with online content. RESULTS: 28 participants were included, and the average age was 27.6 years (standard deviation = 6.8). Almost all participants (96.4%) remained engaged with the WeTest+ program over a 3-week observational period. The majority (92.9%) self-administered the HIV self-test and submitted their test results through the online platform. Overall click-through rates were high (average 67.9%). Participants provided favorable comments about the quality and relevance of the WeTest+ information content, the engaging style of information presentation, and the user-centered features. CONCLUSION: This pilot assessment of WeTest+ supports the promise of this program for promoting HIV self-testing and linkage to in-person services for MSM in China. Findings underscore the utility of a user-centered approach to mHealth program design.

Effects of aerobic exercise or Tai Chi Chuan interventions on problematic mobile phone use and the potential role of intestinal flora: A multi-arm randomized controlled trial.

BACKGROUND: Problematic use of mobile phones (PMPU) has been described as a serious public health issue. METHODS: This study was a parallel three-arm randomized controlled trial and has completed registration (ClinicalTrials.gov Identifier: NCT05843591). Ninety college students with PMPU were randomly assigned to the aerobic exercise group (AE group, n = 30), the Tai Chi Chuan group (TCC group, n = 30), or the wait-list control group (WLC group, n = 30). At the end of the intervention, stool samples from the study participants were collected for biological analysis based on 16 S rDNA amplicon sequencing technology. The primary outcome was addiction symptoms assessed by the Smartphone Addiction Scale-Short Version (SAS-SV). The secondary outcomes are emotional symptoms, physical symptoms, and flora species. RESULTS: Compared with the WLC group, the AE and TCC groups showed reductions in PMPU levels, physical and mental fatigue, but there was no difference between the two groups. Moreover, the effect of increasing self-esteem embodied in the TCC group was not present in the AE group. Compared to the WLC group, the relative abundance of Bacteroidaceae and Bacteroides were lower in the AE group, while the relative abundance of Erysipelotrichaceae and Alistipes were lower in the TCC group. And the relative abundance of Bacteroidaceae, Bacteroides, and Alistipes were significantly and negatively correlated with the decline in PMPU scores. CONCLUSION: AE or TCC is an effective, safe and efficient intervention for college students with PMPU, providing some physiological and psychological benefits and having some impact on their intestinal flora.

Robot-assisted augmented reality surgical navigation based on optical tracking for mandibular reconstruction surgery.

PURPOSE: This work proposes a robot-assisted augmented reality (AR) surgical navigation system for mandibular reconstruction. The system accurately superimposes the preoperative osteotomy plan of the mandible and fibula into a real scene. It assists the doctor in osteotomy quickly and safely under the guidance of the robotic arm. METHODS: The proposed system mainly consists of two modules: the AR guidance module of the mandible and fibula and the robot navigation module. In the AR guidance module, we propose an AR calibration method based on the spatial registration of the image tracking marker to superimpose the virtual models of the mandible and fibula into the real scene. In the robot navigation module, the posture of the robotic arm is first calibrated under the tracking of the optical tracking system. The robotic arm can then be positioned at the planned osteotomy after the registration of the computed tomography image and the patient position. The combined guidance of AR and robotic arm can enhance the safety and precision of the surgery. RESULTS: The effectiveness of the proposed system was quantitatively assessed on cadavers. In the AR guidance module, osteotomies of the mandible and fibula achieved mean errors of 1.61 ± 0.62 and 1.08 ± 0.28 mm, respectively. The mean reconstruction error of the mandible was 1.36 ± 0.22 mm. In the AR-robot guidance module, the mean osteotomy errors of the mandible and fibula were 1.47 ± 0.46 and 0.98 ± 0.24 mm, respectively. The mean reconstruction error of the mandible was 1.20 ± 0.36 mm. CONCLUSIONS: The cadaveric experiments of 12 fibulas and six mandibles demonstrate the proposed system's effectiveness and potential clinical value in reconstructing the mandibular defect with a free fibular flap.

Incidence and prognosis of acute kidney injury versus acute kidney disease among 71 041 inpatients.

Background: Acute kidney disease (AKD) defines patients with acute kidney injury (AKI) or subacute loss of kidney function lasting for >7 days. Little is known about the prognosis of AKD in hospitalized patients. The aim of this study was to investigate the risk factors and prognosis of AKD and to compare different types of acute/subacute renal impairment among Chinese inpatients. Methods: Complete data were available for 71 041 patients for a range of 5-63 months. AKI and AKD were diagnosed based on the Acute Disease Quality Initiative criteria of 2017. Results: Of 71 041 inpatients, 16 098 (22.7%) patients developed AKI or AKD; 5895 (8.3%) AKI patients recovered within 7 days, 5623 (7.9%) AKI patients developed AKD and 4580 (6.4%) patients developed AKD without AKI. Mortality was proportional to stages of AKI and AKD (P < .05), while AKI followed by AKD was associated with a higher risk of long-term mortality [hazard ratio (HR) 4.51] as compared with AKD without AKI (HR 2.25) and recovery from AKI (HR 1.18). The AKD criteria were robustly associated with overall survival [area under the receiver operating characteristic curve (AUROC) 0.71] and de novo CKD (AUROC 0.71), while the AKI criteria showed a relatively lower ability to fit the risk of overall survival (AUROC 0.65) and CKD (AUROC 0.63). Conclusions: AKD and AKD stages are useful clinical definitions for clinical practice, as they predict unfortunate clinical outcomes such as overall long-term mortality and CKD. Research activities should focus on AKD.

Application of a modified osteotomy and positioning integrative template system (MOPITS) based on a truncatable reconstruction model in the precise mandibular reconstruction with fibula free flap: a pilot clinical study.

BACKGROUND: Mandibular defects can greatly affect patients' appearance and functionality. The preferred method to address this issue is reconstructive surgery using a fibular flap. The current personalized guide plate can improve the accuracy of osteotomy and reconstruction, but there are still some problems such as complex design process and time-consuming. Therefore, we modified the conventional template to serve the dual purpose of guiding the mandible and fibula osteotomy and facilitating the placement of the pre-bent titanium. METHODS: The surgery was simulated preoperatively using Computer-Aided Design (CAD) technology. The template and truncatable reconstruction model were produced in the laboratory using 3D printing. After pre-bending the titanium plate according to the contour, the reconstruction model was truncated and the screw trajectory was transferred to form a modified osteotomy and positioning integrative template system (MOPITS). Next, the patient underwent a composite template-guided vascularized fibula flap reconstruction of the mandible. All cases were reviewed for the total operative time and accuracy of surgery. RESULTS: The procedures involved 2-4 fibular segments in 15 patients, averaging 3 fibular segments per procedure. The osteotomy error is 1.01 ± 1.02 mm, while the reconstruction angular error is 1.85 ± 1.69°. The preoperative and postoperative data were compared, and both p > 0.05. During the same operation, implant placement was performed on four patients, with an average operative time of 487.25 ± 60.84 min. The remaining malignant tumor patients had an average operative time of 397.18 ± 73.09 min. The average postoperative hospital stay was 12.95 ± 3.29 days. CONCLUSIONS: This study demonstrates the effectiveness of MOPITS in facilitating precise preoperative planning and intraoperative execution of fibula flap reconstruction. MOPITS represents a promising and reliable tool for reconstructive surgery, particularly for inexperienced surgeons navigating the challenges of mandible defect reconstruction.

Genome-wide identification of the mitogen-activated kinase gene family from Limonium bicolor and functional characterization of LbMAPK2 under salt stress.

BACKGROUND: Mitogen-activated protein kinases (MAPKs) are ubiquitous signal transduction components in eukaryotes. In plants, MAPKs play an essential role in growth and development, phytohormone regulation, and abiotic stress responses. The typical recretohalophyte Limonium bicolor (Bunge) Kuntze has multicellular salt glands on its stems and leaves; these glands secrete excess salt ions from its cells to mitigate salt damage. The number, type, and biological function of L. bicolor MAPK genes are unknown. RESULTS: We identified 20 candidate L. bicolor MAPK genes, which can be divided into four groups. Of these 20 genes, 17 were anchored to 7 chromosomes, while LbMAPK18, LbMAPK19, and LbMAPK20 mapped to distinct scaffolds. Structure analysis showed that the predicted protein LbMAPK19 contains the special structural motif TNY in its activation loop, whereas the other LbMAPK members harbor the conserved TEY or TDY motif. The promoters of most LbMAPK genes carry cis-acting elements related to growth and development, phytohormones, and abiotic stress. LbMAPK1, LbMAPK2, LbMAPK16, and LbMAPK20 are highly expressed in the early stages of salt gland development, whereas LbMAPK4, LbMAPK5, LbMAPK6, LbMAPK7, LbMAPK11, LbMAPK14, and LbMAPK15 are highly expressed during the late stages. These 20 LbMAPK genes all responded to salt, drought and ABA stress. We explored the function of LbMAPK2 via virus-induced gene silencing: knocking down LbMAPK2 transcript levels in L. bicolor resulted in fewer salt glands, lower salt secretion ability from leaves, and decreased salt tolerance. The expression of several genes [LbTTG1 (TRANSPARENT TESTA OF GL1), LbCPC (CAPRICE), and LbGL2 (GLABRA2)] related to salt gland development was significantly upregulated in LbMAPK2 knockdown lines, while the expression of LbEGL3 (ENHANCER OF GL3) was significantly downregulated. CONCLUSION: These findings increase our understanding of the LbMAPK gene family and will be useful for in-depth studies of the molecular mechanisms behind salt gland development and salt secretion in L. bicolor. In addition, our analysis lays the foundation for exploring the biological functions of MAPKs in an extreme halophyte.

Pre-Exposure Prophylaxis Care Continuum for HIV Risk Populations: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Pre-exposure prophylaxis (PrEP) is an effective biomedical strategy for HIV prevention. This umbrella review is aimed at providing a comprehensive summary of the current status of each stage of the PrEP care cascade. A systematic literature search was conducted in PubMed, Embase, and Cochrane. Additionally, a Measurement Tool to Assess Systematic Reviews 2 (AMSTAR-2) tool and Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist were used to evaluate their methodological and reporting quality, respectively. A total of 30 systematic reviews met the inclusion criteria. According to the results of methodological quality assessment, 3 reviews were rated as low, while 27 as critically low. Furthermore, the results of the reporting quality evaluation revealed a mean score of 23.03 for the included reviews. Across all the reviews, awareness of PrEP was generally moderate in all populations, and the acceptability was even higher compared with awareness. Unfortunately, the PrEP uptake among different groups was even less optimal, although the adherence was almost above moderate, and several barriers that hindered the utilization of PrEP were identified, and the most common are as follows: cost, stigma, lack of knowledge, mistrust, low risk perception, and more. Although PrEP has proven to be an effective prevention method to date, the promotion of PrEP failed to achieve the anticipated outcome. To reinforce the generalization of and use of PrEP, and effectively control HIV transmission, it is urgent to identify the underlying causes of low uptake rates so that efficient interventions can be implemented.

Rapid multi-task diagnosis of oral cancer leveraging fiber-optic Raman spectroscopy and deep learning algorithms.

Introduction: Oral cancer, a predominant malignancy in developing nations, represents a global health challenge with a five-year survival rate below 50%. Nonetheless, substantial reductions in both its incidence and mortality rates can be achieved through early detection and appropriate treatment. Crucial to these treatment plans and prognosis predictions is the identification of the pathological type of oral cancer. Methods: Toward this end, fiber-optic Raman spectroscopy emerges as an effective tool. This study combines Raman spectroscopy technology with deep learning algorithms to develop a portable intelligent prototype for oral case analysis. We propose, for the first time, a multi-task network (MTN) Raman spectroscopy classification model that utilizes a shared backbone network to simultaneously achieve different clinical staging and histological grading diagnoses. Results: The developed model demonstrated accuracy rates of 94.88%, 94.57%, and 94.34% for tumor staging, lymph node staging, and histological grading, respectively. Its sensitivity, specificity, and accuracy compare closely with the gold standard: routine histopathological examination. Discussion: Thus, this prototype proposed in this study has great potential for rapid, non-invasive, and label-free pathological diagnosis of oral cancer.

Inhibition of acid sphingomyelinase reduces reactive astrocyte secretion of mitotoxic extracellular vesicles and improves Alzheimer's disease pathology in the 5xFAD mouse.

In Alzheimer's disease (AD), reactive astrocytes produce extracellular vesicles (EVs) that affect mitochondria in neurons. Here, we show that Aß-induced generation of the sphingolipid ceramide by acid sphingomyelinase (A-SMase) triggered proinflammatory cytokine (C1q, TNF-α, IL-1α) release by microglia, which induced the reactive astrocytes phenotype and secretion of EVs enriched with ceramide. These EVs impeded the capacity of neurons to respond to energy demand. Inhibition of A-SMase with Arc39 and Imipramine reduced the secretion of cytokines from microglia, prompting us to test the effect of Imipramine on EV secretion and AD pathology in the 5xFAD mouse model. Brain derived-EVs from 5xFAD mice treated with Imipramine contained reduced levels of the astrocytic marker GFAP, ceramide, and Aß and did not impair mitochondrial respiration when compared to EVs derived from untreated 5xFAD brain. Consistently, Imipramine-treated 5xFAD mice showed reduced AD pathology. Our study identifies A-SMase inhibitors as potential AD therapy by preventing cyotokine-elicited secretion of mitotoxic EVs from astrocytes.

Giant calcifying epithelial odontogenic tumor after I-125 seed implantation: A case report.

Calcifying Epithelial Odontogenic Tumor (CEOT), also known as Pindborg tumor, is a rare odontogenic benign tumor. It was first reported by Thoma and Goldman in 1946 and defined as an independent tumor by Pindborg in 1957. Herein, we reported a CEOT case involving most of the mandible after I-125 implantation in a 53-year-old man. We cooperated with governmental and hospital departments to resect the tumors, reconstruct the mandible with a fibular flap graft, and properly dispose of the radioactive particles.

Finerenone Added to RAS/SGLT2 Blockade for CKD in Alport Syndrome. Results of a Randomized Controlled Trial with Col4a3-/- Mice.

SIGNIFICANCE STATEMENT: We hypothesized that triple therapy with inhibitors of the renin-angiotensin system (RAS), sodium-glucose transporter (SGLT)-2, and the mineralocorticoid receptor (MR) would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression in Col4a3 -deficient mice, a model of Alport syndrome. Late-onset ramipril monotherapy or dual ramipril/empagliflozin therapy attenuated CKD and prolonged overall survival by 2 weeks. Adding the nonsteroidal MR antagonist finerenone extended survival by 4 weeks. Pathomics and RNA sequencing revealed significant protective effects on the tubulointerstitium when adding finerenone to RAS/SGLT2 inhibition. Thus, triple RAS/SGLT2/MR blockade has synergistic effects and might attenuate CKD progression in patients with Alport syndrome and possibly other progressive chronic kidney disorders. BACKGROUND: Dual inhibition of the renin-angiotensin system (RAS) plus sodium-glucose transporter (SGLT)-2 or the mineralocorticoid receptor (MR) demonstrated additive renoprotective effects in large clinical trials. We hypothesized that triple therapy with RAS/SGLT2/MR inhibitors would be superior to dual RAS/SGLT2 blockade in attenuating CKD progression. METHODS: We performed a preclinical randomized controlled trial (PCTE0000266) in Col4a3 -deficient mice with established Alport nephropathy. Treatment was initiated late (age 6 weeks) in mice with elevated serum creatinine and albuminuria and with glomerulosclerosis, interstitial fibrosis, and tubular atrophy. We block-randomized 40 male and 40 female mice to either nil (vehicle) or late-onset food admixes of ramipril monotherapy (10 mg/kg), ramipril plus empagliflozin (30 mg/kg), or ramipril plus empagliflozin plus finerenone (10 mg/kg). Primary end point was mean survival. RESULTS: Mean survival was 63.7±10.0 days (vehicle), 77.3±5.3 days (ramipril), 80.3±11.0 days (dual), and 103.1±20.3 days (triple). Sex did not affect outcome. Histopathology, pathomics, and RNA sequencing revealed that finerenone mainly suppressed the residual interstitial inflammation and fibrosis despite dual RAS/SGLT2 inhibition. CONCLUSION: Experiments in mice suggest that triple RAS/SGLT2/MR blockade may substantially improve renal outcomes in Alport syndrome and possibly other progressive CKDs because of synergistic effects on the glomerular and tubulointerstitial compartments.

The S1P receptor 1 antagonist Ponesimod reduces TLR4-induced neuroinflammation and increases Aß clearance in 5XFAD mice.

BACKGROUND: Previously, we showed that the sphingosine-1-phosphate (S1P) transporter spinster 2 (Spns2) mediates activation of microglia in response to amyloid ß peptide (Aß). Here, we investigated if Ponesimod, a functional S1P receptor 1 (S1PR1) antagonist, prevents Aß-induced activation of glial cells and Alzheimer's disease (AD) pathology. METHODS: We used primary cultures of glial cells and the 5XFAD mouse model to determine the effect of Aß and Ponesimod on glial activation, Aß phagocytosis, cytokine levels and pro-inflammatory signaling pathways, AD pathology, and cognitive performance. FINDINGS: Aß42 increased the levels of TLR4 and S1PR1, leading to their complex formation. Ponesimod prevented the increase in TLR4 and S1PR1 levels, as well as the formation of their complex. It also reduced the activation of the pro-inflammatory Stat1 and p38 MAPK signaling pathways, while activating the anti-inflammatory Stat6 pathway. This was consistent with increased phagocytosis of Aß42 in primary cultured microglia. In 5XFAD mice, Ponesimod decreased the levels of TNF-α and CXCL10, which activate TLR4 and Stat1. It also increased the level of IL-33, an anti-inflammatory cytokine that promotes Aß42 phagocytosis by microglia. As a result of these changes, Ponesimod decreased the number of Iba-1+ microglia and GFAP+ astrocytes, and the size and number of amyloid plaques, while improving spatial memory as measured in a Y-maze test. INTERPRETATION: Ponesimod targeting S1PR1 is a promising therapeutic approach to reprogram microglia, reduce neuroinflammation, and increase Aß clearance in AD. FUNDING: NIHR01AG064234, RF1AG078338, R21AG078601, VAI01BX003643.

Ganoderenic acid D-loaded functionalized graphene oxide-based carrier for active targeting therapy of cervical carcinoma.

Ganoderenic acid D (GAD), extracted from the Chinese herb Ganoderma lucidum, was loaded onto a graphene oxide-polyethylene glycol-anti-epidermal growth factor receptor (GO-PEG-EGFR) carrier to develop a targeting antitumor nanocomposite (GO-PEG@GAD). The carrier was fabricated from PEG and anti-EGFR aptamer modified GO. Targeting was mediated by the grafted anti-EGFR aptamer, which targets the membrane of HeLa cells. Physicochemical properties were characterized by transmission electron microscopy, dynamic light scattering, X-ray powder diffraction, and Fourier transform infrared spectroscopy. High loading content (77.3 % ± 1.08 %) and encapsulation efficiency (89.1 % ± 2.11 %) were achieved. Drug release continued for approximately 100 h. The targeting effect both in vitro and in vivo was confirmed by confocal laser scanning microscopy (CLSM) and imaging analysis system. The mass of the subcutaneous implanted tumor was significantly decreased by 27.27 ± 1.23 % after treatment with GO-PEG@GAD compared with the negative control group. Moreover, the in vivo anti-cervical carcinoma activity of this medicine was due to activation of the intrinsic mitochondrial pathway.

Innovative use of a self-expanding valve for valve-in-valve transcatheter mitral valve replacement: experience from a four-year single-center study.

Background: Valve-in-valve transcatheter mitral valve replacement (ViV-TMVR) is a minimally invasive option for patients with bioprosthetic mitral valve failure. Since January 2019, our center has been using a new innovative option, J-Valve, to treat patients with bioprosthetic mitral valve failure who were at high risk for open heart surgery. The aim of this study is to explore the effectiveness and safety of J-Valve and report the results from the four-year follow-up period of the innovative application of the transcatheter valve. Methods: Patients who underwent the ViV-TMVR procedure between January 2019 and September 2022 in our center were included in the study. J-Valve™ system (JC Medical Inc., Suzhou, China) with three U-shape grippers was used for ViV-TMVR via transapical approach. Data on survival, complications, transthoracic echocardiographic results, New York Heart Association functional class in heart failure, and patient-reported health-related quality of life according to the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) were collected during the four-year follow up. Results: Thirty-three patients (mean age 70.1 ± 1.1 years, 13 men) were included and received ViV-TMVR. The surgery success rate was 97%: only one patient was converted to open-heart surgery due to intraoperative valve embolization to the left ventricle. During the first 30 days all-cause mortality was 0%, risk of stroke 2.5% and risk of mild paravalvular leak 15.2%; mitral valve hemodynamics improved (179.7 ± 8.9 at 30 days vs. 269 ± 49 cm/s at baseline, p < 0.0001). Median time from operation to discharge was six days, and there were no readmissions within 30 days from operation. The median and maximum follow-up durations were 28 and 47 months, respectively; during the entire follow-up, all-cause mortality was 6.1%, and the risk of cerebral infarction 6.1%. Cox regression analysis did not identify any variables significantly associated with survival. The New York Heart Association functional class and the KCCQ-12 score improved significantly compared with their preoperative values. Conclusion: The use of J-Valve for ViV-TMVR is safe and effective with a high success rate, low mortality and very few associated complications, representing an alternative surgical strategy for the elderly, high-risk patients with bioprosthetic mitral valve failure.

Novel Isolation Method Reveals Sex-Specific Composition and Neurotoxicity of Small Extracellular Vesicles in a Mouse Model of Alzheimer's Disease.

We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer's disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aß. ExoView analysis showed that female mice contained more GFAP and Aß-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aß. Moreover, sEVs from female brains had more acid sphingomyelinase (ASM) and ceramide, an enzyme and its sphingolipid product important for EV formation and Aß binding to EVs, respectively. We confirmed the function of ASM in EV formation and Aß binding using co-labeling and proximity ligation assays, showing that ASM inhibitors prevented complex formation between Aß and ceramide in primary cultured astrocytes. Finally, our study demonstrated that sEVs from female 5xFAD mice were more neurotoxic than those from males, as determined by impaired mitochondrial function (Seahorse assays) and LDH cytotoxicity assays. Our study suggests that sex-specific sEVs are functionally distinct markers for AD and that ASM is a potential target for AD therapy.

Experimental Study on the Influence of Transverse Crack on Chloride Ingress in Concrete Slab Track of High-Speed Railway.

The concrete track slab and the base slab of the high-speed railway CRTS II track structure are prone to transverse cracks in the initial service period, which are subjected to environmental action and train load. In order to investigate the influence of transverse cracks on chloride ingress of concrete track slab and base slab in a coastal environment, drying-wetting cycle chloride erosion tests were carried out on reinforced concrete track slab and base slab specimens with cracks ranging from 0 mm to 0.6 mm, subjected to continuous bending moment. The chloride ion concentration of concrete along the depth direction was collected during the test process. The experimental results show that the chloride ion concentration of concrete at the crack section is much higher than that at the intact section, and it increases with the increase of crack width in the range of 0.2 mm to 0.6 mm. A chloride diffusion coefficient model of cracked concrete is proposed for slab track based on the experimental results, which can comprehensively consider the effects of surface chloride ion concentration, chloride binding effect, time-varying effect, temperature, relative humidity, and transverse crack width.

Regulation of microglia related neuroinflammation contributes to the protective effect of Gelsevirine on ischemic stroke.

Stroke, especially ischemic stroke, is an important cause of neurological morbidity and mortality worldwide. Growing evidence suggests that the immune system plays an intricate function in the pathophysiology of stroke. Gelsevirine (Gs), an alkaloid from Gelsemium elegans, has been proven to decrease inflammation and neuralgia in osteoarthritis previously, but its role in stroke is unknown. In this study, the middle cerebral artery occlusion (MCAO) mice model was used to evaluate the protective effect of Gs on stroke, and the administration of Gs significantly improved infarct volume, Bederson score, neurobiological function, apoptosis of neurons, and inflammation state in vivo. According to the data in vivo and the conditioned medium (CM) stimulated model in vitro, the beneficial effect of Gs came from the downregulation of the over-activity of microglia, such as the generation of inflammatory factors, dysfunction of mitochondria, production of ROS and so on. By RNA-seq analysis and Western-blot analysis, the JAK-STAT signal pathway plays a critical role in the anti-inflammatory effect of Gs. According to the results of molecular docking, inhibition assay, and thermal shift assay, the binding of Gs on JAK2 inhibited the activity of JAK2 which inhibited the over-activity of JAK2 and downregulated the phosphorylation of STAT3. Over-expression of a gain-of-function STAT3 mutation (K392R) abolished the beneficial effects of Gs. So, the downregulation of JAK2-STAT3 signaling pathway by Gs contributed to its anti-inflammatory effect on microglia in stroke. Our study revealed that Gs was benefit to stroke treatment by decreasing neuroinflammation in stroke as a potential drug candidate regulating the JAK2-STAT3 signal pathway.

Longitudinal association between problematic smartphone use and sleep disorder among Chinese college students during the COVID-19 pandemic.

BACKGROUND: Problematic smartphone use (PSU) and sleep disorders (SD) are common public health problems among college students. While previous cross-sectional studies have found a relationship between PSU and SD, the causal direction of this relationship remains unclear. This study aims to examine the longitudinal changes of PSU and SD during the COVID-19 pandemic, determine the causal relationship between them, and identify confounding factors that affect this association. METHODS: The study sample consisted of 1186 Chinese college students (47.7% male) with a mean age of 18.08 years. Participants completed the Smartphone Addiction Scale - Short Version (SAS-SV) and the Pittsburgh Sleep Quality Index (PSQI) at both baseline and follow-up surveys, conducted one year apart. The cross-lagged panel model (CLPM) was used to examine the causal relationship between PSU and SD, stratified by gender and duration of daily physical activity. The fixed effect panel regression was used to confirm the findings of CLPM. RESULTS: The results of the CLPM analysis showed a significant bidirectional relationship between PSU and SD for the overall sample, which was consistent with the fixed effects model findings. However, subgroup analyses revealed that the bidirectional association disappeared among males or those who engaged in daily physical activity for more than 1 h. CONCLUSIONS: Our study shows a significant bidirectional association between PSU and SD, with variations across gender and daily physical activity levels. Encouraging physical activity may serve as a potential intervention to disrupt the bidirectional association between PSU and SD, which has important implications for public health strategies aimed at reducing the negative consequences of PSU and SD.