Risk factors for preoperative frailty in older patients with gastric cancer: a systematic review and meta-analysis.

PURPOSE: To summarize the available evidence on risk factors for preoperative frailty in older gastric cancer patients. METHODS: We comprehensively searched the CNKI, Wanfang, VIP, CBM, PubMed, Embase, The Cochrane Library, Web of Science, and CINAHL databases for preoperative articles on risk factors for frailty in older gastric cancer patients. The search was conducted from the time of construction of the library to January 27, 2024, with no language restrictions. The quality of the included studies was rated by the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality tool. RESULTS: A total of 20 studies were included, including 16 cohort studies and 4 cross-sectional studies, with a total sample size of 51,717 individuals. The results of the meta-analysis showed that age, albumin, hemoglobin, cancer stage III-IV, Charlson Comorbidity Index score ≥ 3, Eastern Cooperative Oncology Group score > 2, American Society of Anesthesiologists score > 2, smoking, nutritional risk, high school degree or above, and sleep disorders are the main influencing factors for the occurrence of preoperative frailty in older gastric cancer patients. Among them, high school degree or above was a protective factor. CONCLUSIONS: Our study provides valid evidence of risk factors for preoperative frailty in older patients with gastric cancer and informs clinical healthcare professionals to make targeted interventions.

Swift-Eye: Towards Anti-blink Pupil Tracking for Precise and Robust High-Frequency Near-Eye Movement Analysis with Event Cameras.

Eye tracking has shown great promise in many scientific fields and daily applications, ranging from the early detection of mental health disorders to foveated rendering in virtual reality (VR). These applications all call for a robust system for high-frequency near-eye movement sensing and analysis in high precision, which cannot be guaranteed by the existing eye tracking solutions with CCD/CMOS cameras. To bridge the gap, in this paper, we propose Swift-Eye, an offline precise and robust pupil estimation and tracking framework to support high-frequency near-eye movement analysis, especially when the pupil region is partially occluded. Swift-Eye is built upon the emerging event cameras to capture the high-speed movement of eyes in high temporal resolution. Then, a series of bespoke components are designed to generate high-quality near-eye movement video at a high frame rate over kilohertz and deal with the occlusion over the pupil caused by involuntary eye blinks. According to our extensive evaluations on EV-Eye, a large-scale public dataset for eye tracking using event cameras, Swift-Eye shows high robustness against significant occlusion. It can improve the IoU and F1-score of the pupil estimation by 20% and 12.5% respectively, compared with the second-best competing approach, when over 80% of the pupil region is occluded by the eyelid. Lastly, it provides continuous and smooth traces of pupils in extremely high temporal resolution and can support high-frequency eye movement analysis and a number of potential applications, such as mental health diagnosis, behaviour-brain association, etc. The implementation details and source codes can be found at https://github.com/ztysdu/Swift-Eye.

The characterization of protein lactylation in relation to cardiac metabolic reprogramming in neonatal mouse hearts.

In mammals, the neonatal heart can regenerate upon injury within a short time after birth, while adults lose this ability. Metabolic reprogramming has been demonstrated to be critical for cardiomyocyte proliferation in the neonatal heart. Here, we reveal that cardiac metabolic reprogramming could be regulated by altering global protein lactylation. By performing 4D label-free proteomics and lysine lactylation (Kla) omics analyses in mouse hearts at postnatal days 1, 5, and 7, 2297 Kla sites from 980 proteins are identified, among which 1262 Kla sites from 409 proteins are quantified. Functional clustering analysis reveals that the proteins with altered Kla sites are mainly involved in metabolic processes. The expression and Kla levels of proteins in glycolysis show a positive correlation while a negative correlation in fatty acid oxidation. Furthermore, we verify the Kla levels of several differentially modified proteins, including ACAT1, ACADL, ACADVL, PFKM, PKM, and NPM1. Overall, our study reports a comprehensive Kla map in the neonatal mouse heart, which will help to understand the regulatory network of metabolic reprogramming and cardiac regeneration.

Filtration of polystyrene nanoplastics with different functional groups by natural mineral materials: Performance and mechanisms.

Optimizing nanoplastics (NPs) removal performance of rapid sand filter (RSF) in water treatment plants is significant for NP pollution prevention and remediation. This study investigated the application prospect of natural granular manganese sand, zeolite and limestone in RSF for NP removal through column experiments. Pristine, amino-modified, and carboxyl-modified polystyrene NPs (100 nm) were selected as experimental subjects. Quartz sand filter showed negligible NP removal, zeolite and manganese sand showed no obvious optimization on NP filtration. Limestone amended RSF significantly enhanced the removal of three NPs, the removal efficiency increased with decreasing size and increasing limestone grains dosage. The excellent performance of limestone was attributed to its special physicochemical properties in terms of synthetical action of electrostatic interaction, cationic bridging and especially the surface roughness morphology, and the mechanisms overcame the influence of functional groups of NPs. The results indicate the prospective applications of granular limestone in RSF for NP filtration.

Safety and efficacy of glibenclamide on cerebral oedema following aneurysmal subarachnoid haemorrhage: a randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Glibenclamide has garnered attention due to its multifaceted neuroprotective effects in cases of acute central nervous system injury. We initiated a trial to explore the effectiveness and safety of a high dose of glibenclamide in the management of cerebral oedema following aneurysmal subarachnoid haemorrhage (aSAH). METHODS: This trial constituted a single-centre, randomised clinical study. Half of the 56 patients assigned to the glibenclamide group received 15 mg of glibenclamide tablets daily for 10 days (5 mg, three times/day). The primary outcome was the proportion of patients achieving the subarachnoid haemorrhage early brain oedema score dichotomy (defined as Subarachnoid Haemorrhage Early Brain Oedema Score 0-2) at the 10-day postmedication. The secondary outcome of cerebral oedema was the concentration of sulfonylurea receptor 1-transient receptor potential melastatin 4 (SUR1-TRPM4) in the plasma and cerebrospinal fluid. RESULTS: We enrolled 56 patients diagnosed with aSAH, who were admitted to the neurosurgery intensive care unit between 22 August 2021 and 25 April 2023. The primary outcome revealed that the glibenclamide group exhibited a notably higher proportion of mild cerebral oedema in comparison to the placebo group (60.7% vs 42.9%, adjusted OR: 4.66, 95% CI 1.14 to 19.10, p=0.032). Furthermore, the concentration of SUR1-TRPM4 in the cerebrospinal fluid of the glibenclamide group was significantly higher than the placebo group (p=0.0002; p=0.026), while the plasma TRPM4 concentration in the glibenclamide group was significantly lower than the placebo group (p=0.001). CONCLUSION: Oral administration of high-dose glibenclamide notably reduced radiological assessment of cerebral oedema after 10 days of medication. Significant alterations were also observed in the concentration of SUR1-TRPM4 in plasma and cerebrospinal fluid. However, it is worth noting that glibenclamide was associated with a higher incidence of hypoglycaemia. Larger trials are warranted to evaluate the potential benefits of glibenclamide in mitigating swelling and then improving neurological function. TRIAL REGISTRATION NUMBER: ChiCTR2100049908.

Safety and efficacy of dual antiplatelet drugs for stent-assisted embolization on risk of stroke and prognosis in patients with ruptured intracranial aneurysms: One center results of CIAP-5 clinical trial.

BACKGROUND: Although stent-assisted coiling embolization (SAC) has been associated with a higher risk of ischemic and hemorrhagic complications, the use of SAC continues to rise for treating ruptured intracranial aneurysms (RIAs). This study aims to assess the safety and effectiveness of dual antiplatelet therapy (DAPT) in the context of RIAs. METHODS: We conducted a retrospective analysis at a single center, involving patients with aneurysmal subarachnoid hemorrhage (aSAH) between May 1, 2017 and December 31, 2021. Patients were categorized into two groups: the SAC group and the non-SAC (NSC) group. Patients in the SAC group received DAPT. We compared modified Rankin Scale (mRS) score, along with hemorrhagic and ischemic complications, between the two groups to evaluate the safety and efficacy of DAPT for SAC. RESULTS: The study included a total of 541 patients, of whom 38 (7.0%) experienced hemorrhagic complications and 48 (8.9%) developed ischemic complications. Additionally, 99 (18.3%) and 84 (15.5%) had poor clinical outcomes at discharge and 6 months, respectively. However, no statistically significant differences were observed between the two groups. Our analysis revealed that aneurysm location in the posterior circulation was a significant risk factor for an unfavorable prognosis when antiplatelet drugs were used following SAC (p = 0.025). CONCLUSIONS: Administering antiplatelet drugs after SAC for RIAs has demonstrated both safety and effectiveness. However, caution should be exercised when considering this treatment strategy for RIAs located in the posterior circulation due to the potentially elevated risk.

Osteopontin modulates microglial activation states and attenuates inflammatory responses after subarachnoid hemorrhage in rats.

AIMS: Osteopontin (OPN) has demonstrated neuroprotective effects in various stroke models. Its role in neuroinflammation after brain injury remains to be elucidated. This study aims to clarify the effect of OPN on neuroinflammation, particularly on the functional states of microglia after subarachnoid hemorrhage (SAH). METHODS: 77 rats were randomly divided into the following groups: Sham, SAH 24 h, SAH + rOPN, SAH + Vehicle (PBS), SAH + OPN siRNA, and SAH + Scr siRNA, SAH + rOPN+Fib-14 and SAH + rOPN+DMSO. Modified Garcia and beam balance tests were used to evaluate neurobehavioral outcomes. Semi-quantitative immunofluorescence staining was performed to measure expression of myeloperoxidase (MPO) and microglia activation state markers CD16, CD206 after SAH and recombinant OPN treatment. The quantification of microglia activation and functional markers CD16, CD206, TNF-α and IL-10 were further evaluated using Western-blotting. RESULTS: Nasal administration of rOPN improved neurological dysfunction, attenuated neutrophil infiltration, and decreased expression of phenotypic and functional markers of pro-inflammatory microglia CD16 and TNF-α. It also promoted an anti-inflammatory microglial state, as evidenced by increased expression of CD206 and IL-10. Furthermore, after blocking the phosphorylation of FAK signaling, the effects of rOPN on microglial activation states were partially reversed. The downstream pathways of STAT3 and NF-κB also exhibited consistent changes, suggesting the involvement of the STAT3 and NF-κB pathways in OPN's modulation of microglial activation via integrin-FAK signaling. CONCLUSION: OPN attenuates inflammatory responses after SAH by promoting an anti-inflammatory microglial state, potentially mediated through the integrin-FAK-STAT3 and NF-κB signaling pathways.

A novel "prime and pull" strategy mediated by the combination of two dendritic cell-targeting designs induced protective lung tissue-resident memory T cells against H1N1 influenza virus challenge.

Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRT‒PCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel "prime and pull" strategy for addressing the production of protective TRM cells in vaccine design.

Effects of unimodal or multimodal prehabilitation on patients undergoing surgery for esophagogastric cancer: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of unimodal or multimodal prehabilitation on patients undergoing surgery for esophagogastric cancer. METHODS: We conducted a systematic search of the PubMed, Embase, CINAHL, Web of Science, and Cochrane Library (CENTRAL) databases from database inception to May 5, 2023, for randomized controlled trials (RCTs) and cohort studies that investigated prehabilitation in the context of esophagogastric cancer. A random-effects model was used for meta-analysis. RESULTS: We identified 2,994 records and eventually included 12 studies (6 RCTs and 6 cohort studies) with a total of 910 patients. According to random-effects pooled estimates, prehabilitation reduced the incidence of all complications (RR = 0.79, 95% CI: 0.66 to 0.93, P = 0.006), pulmonary complications (RR = 0.61, 95% CI: 0.47 to 0.79, P = 0.0002), and severe complications (RR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002), and shortened the length of stay (MD = -1.92, 95% CI: -3.11 to -0.73, P = 0.002) compared to usual care. However, there were no statistically significant differences in 30-day readmission rates or in-hospital mortality. Subgroup analysis showed that multimodal prehabilitation was effective in reducing the risk of all complications and severe complications, while unimodal prehabilitation was not. CONCLUSIONS: Our findings suggested that prehabilitation may be beneficial in reducing postoperative complications and length of stay. We recommend preoperative prehabilitation to improve postoperative outcomes and hasten recovery following esophagogastric cancer surgery, and multimodal prehabilitation seems to be more advantageous in reducing complications. However, further studies are needed to confirm these results.

NL-1 Promotes PINK1-Parkin-Mediated Mitophagy Through MitoNEET Inhibition in Subarachnoid Hemorrhage.

NL-1 is a mitoNEET ligand known for its antileukemic effects and has recently shown neuroprotective effects in an ischemic stroke model. However, its underlying process in subarachnoid hemorrhage (SAH) is still unclear. Thus, we aimed to investigate the possible mechanism of NL-1 after SAH in rats. 112 male adult Sprague-Dawley rats were used for experiments. SAH model was performed with endovascular perforation. Rats were dosed intraperitoneally (i.p.) with NL-1 (3 mg/kg, 10 mg/kg, 30 mg/kg) or a vehicle (10% DMSO aqueous solution) at 1 h after SAH. A novel mitophagy inhibitor liensinine (60 mg/kg) was injected i.p. 24 h before SAH. SAH grades, short-term and long-term neurological scores were measured for neurobehavior. TdTmediated dUTP nick end labeling (TUNEL) staining, dihydroethidium (DHE) staining and western blot measurements were used to detect the outcomes and mechanisms of NL-1 administration. NL-1 treatment significantly improved short-term neurological behavior in Modified Garcia and beam balance sores in comparison with SAH + vehicle group. NL-1 administration also increased mitoNEET which induced phosphatase and tensin-induced kinase 1 (PINK1), Parkin and LC3II related mitophagy compared with SAH + vehicle group. In addition, the expressions of apoptotic protein Cleaved Caspase-3 and oxidative stress related protein Romo1 in NL-1 treatment group were reversed from SAH + vehicle group. Meanwhile, NL-1 treatment notably reduced TUNEL-positive cells, DHE-positive cells compared with SAH + vehicle group. NL-1 treatment notably improved long-term neurological behavior in rotarod and water maze tests compared to SAH + vehicle group. However, the administration of liensinine may inhibit the treatment effect of NL-1, leading to reduced expression of mitophagy markers Pink1, Parkin, LC3I/II, and increased expressions of Romo1 and Cleaved Caspase-3. NL-1 induced PINK1/PARKIN related mitophagy via mitoNEET, which reduced oxidative stress and apoptosis in early brain injury after SAH in rats. NL-1 may serve as a prospective drug for the treatment of SAH.

Bidirectional Mendelian randomization analysis of the genetic association between primary lung cancer and colorectal cancer.

BACKGROUND: With the development and popularization of low-dose chest CT technology, the diagnosis and survival rates of patients with early lung cancer (LC) have significantly improved. The occurrence of colorectal cancer (CRC) as the second primary cancer (SPC) in primary lung cancer (PLC) survivors has become an essential factor affecting the prognosis of early LC. This study explored the potential association between PLC and CRC genetically, laying a foundation for developing SPC-CRC prevention strategies after primary early LC. METHODS: Based on a two-sample bidirectional Mendelian randomization (MR) design, this study systematically screened genetic instrumental variables (IVs) based on the genome-wide association studies (GWAS) of PLC and CRC, applied inverse variance weighted (IVW) as the main method to assess the incidence association between the two cancers, and used a variety of other MR methods for supplementary analysis. Finally, the Genetic Risk Scores (GRS) method was used for secondary analysis to verify the results robustness further. RESULTS: From LC to CRC forward MR analysis, 20 genetic IVs of overall LC, 15 genetic IVs of squamous cell lung carcinoma (LUSC), and 10 genetic IVs of adenocarcinoma of the lung (LUAD) were screened. In the reverse MR analysis from CRC to LC, 47 genetic IVs for overall CRC, 37 for colon cancer, and 25 for rectal cancer were screened. The IVW method and a variety of MR methods all found that overall LC and CRC were significantly associated at the genetic level. Subgroup analysis also showed that LUSC was associated with CRC. And the results of the GRS method were consistent with those of the main analysis, confirming the robustness of the study. Our MR study found an association between LC and CRC, with an increased risk of SPC-CRC following PLC, especially LUSC. Our study provides an essential basis for the precise prevention of SPC-CRC after PLC, suggesting that we should pay more attention to the population with a history of PLC in clinical work, and pay close attention to the incidence of SPC-CRC, and carry out intervention and treatment as soon as possible.

Pleiotropic Microenvironment Remodeling Micelles for Cerebral Ischemia-Reperfusion Injury Therapy by Inhibiting Neuronal Ferroptosis and Glial Overactivation.

Reperfusion injury presents a significant obstacle to neuronal survival following successful recanalization in ischemic stroke, which is characterized by intricate pathophysiological processes comprising numerous interconnected pathways. Oxidative stress-induced neuronal ferroptosis and the overactivation of glial cells play important roles in this phenomenon. In this study, we developed a targeted cross-linked micelle loaded with idebenone to rescue the ischemic penumbra by inhibiting neuronal ferroptosis and glial overactivation. In rat models, the CREKA peptide-modified micelles accumulate in the damaged brain via binding to microthrombi in the ipsilateral microvessels. Upon reactive oxygen species (ROS) stimulation, diselenide bonds within the micelles are transformed to hydrophilic seleninic acids, enabling synchronized ROS consumption and responsive drug release. The released idebenone scavenges ROS, prevents oxidative stress-induced neuronal ferroptosis, attenuates glial overactivation, and suppresses pro-inflammatory factors secretion, thereby modulating the inflammatory microenvironment. Finally, this micelle significantly reinforces neuronal survival, reduces infarct volume, and improves behavioral function compared to the control groups. This pleiotropic therapeutic micelle provides a proof-of-concept of remodeling the lesion microenvironment by inhibiting neuronal ferroptosis and glial overactivation to treat cerebral ischemia-reperfusion injury.

Chicken dendritic cell-targeting nanobodies mediated improved protective effects against H9N2 influenza virus challenge in a homologous sequential immunization study.

Global poultry production is still severely affected by H9N2 avian influenza virus (AIV), and the development of a novel universal AIV vaccine is still urgently needed. Neuraminidase (NA) has recently been shown to be an efficient conserved protective antigen. In this study, we fused the extracellular region of the NA gene with a ferritin cassette (pYL281), which resulted in self-assembled 24-mer nanoparticles with the NA protein displayed outside the nanoparticles. In addition, a chicken dendritic cell-targeting nanobody-phage74 was also inserted ahead of the NA protein to yield pYL294. Incubation with chicken bone marrow-derived dendritic cells (chBMDCs) showed that the DC-targeting nanoparticles purified from the pYL294 strain significantly increased the maturation of chBMDCs, as shown by increased levels of CCL5, CCR7, CD83 and CD86 compared with nontargeting proteins. Then, a chicken study was performed using Salmonella oral administration together with intranasal boost with purified proteins. Compared with the other groups, oral immunization with Salmonella harboring pYL294 followed by intranasal boost with purified DC-targeting nanoparticles dramatically increased the humoral IgY and mucosal IgA antibody response, as well as increased the cellular immune response, as shown by elevated splenic lymphocyte proliferation and intracellular mRNA levels of IL-4 and IFN-γ. Finally, sequential immunization with DC-targeting nanoparticles showed increased protection against G57 subtype H9N2 virus challenge compared with other groups, as shown by significantly decreased virus RNA copy numbers in oropharyngeal washes (Days 3, 5 and 7 post challenge) and cloacal washes (Day 7), significantly decreased lung virus titers on Day 5 post challenge and increased body weight gains during the challenge.