Role of membrane fouling layer in microbial fuel cell-membrane bioreactor (MFC-MBR) for controlling sulfamethoxazole and corresponding resistance genes.

Integrated MFC-MBR systems effectively remove antibiotics and control the release of antibiotic resistance genes (ARGs). However, the fouling layers on membranes can potentially act as reservoirs for ARGs. This study aims to elucidate the roles of membrane fouling layers and levels in influencing sulfamethoxazole (SMX) removal and ARGs control within an MFC-MBR system. Our findings demonstrate that low-intensity bioelectricity (400-500 mV) mitigates membrane fouling rates. The membrane fouling layer significantly contributes (39%-47%) to SMX removal compared to the cathode/anode zones. Higher extracellular polymeric substance (EPS) content and a lower protein/polysaccharide (PN/PS) ratio favor SMX removal by the membrane fouling layer. Across different levels of membrane fouling, the PN/PS ratio rather than EPS concentration plays a crucial role in SMX removal efficiency. The MFC-MBR with low fouling achieved superior SMX removal (69.1%) compared to medium (54.3%) and high fouling conditions (46.8%). The presence of ARGs in the membrane fouling layer increases with fouling formation, with intrinsic ARGs prevailing. Dense membrane fouling layers effectively retain ARGs, thereby reducing the risk of extracellular ARGs (eARGs) diffusion in effluents. These results provide insights into controlling ARGs in MFC-MBR systems and underscore the significant role of membrane fouling layers in antibiotics and ARGs removal.

Chip-scale integrated holographic devices based on top-emitting vertical cavity surface emitting lasers.

Holography technology is considered the ultimate three-dimensional (3D) visualization technology in the future. However, conventional methods for achieving holography generally utilize discrete optical components and off-chip laser sources, resulting in a large size and high complexity, which are undesirable for practical applications. In this Letter, chip-scale integrated holographic devices are realized by integrating top-emitting vertical cavity surface emitting lasers (VCSELs) with micro holograms printed by 3D femtosecond laser nanoprinting technology. The VCSELs are designed to operate in a single fundamental mode with a Gaussian emission profile. Then the Gaussian beams are phase-modulated by the integrated micro holograms designed by the Gerchberg-Saxton (GS) algorithm and the target holographic images can be displayed behind the holograms. Such integrated holographic devices are of micron size and can be easily scaled into arrays with arbitrary channels on-demand, which are important for achieving miniaturized and portable holographic imaging systems.

The association of the severity of Omicron with menstrual and premenstrual syndrome among reproductive age women in China: a cross-sectional study.

This study aimed to investigate changes in menstruation and the association of the severity of Omicron with menstruation after the nationwide outbreak of COVID-19 in China. A cross-sectional study adopted an electronic questionnaire to conduct an anonymous online survey. The survey targeted women of reproductive age who had been infected with SARS-CoV-2, and were menstruating regularly in the six months prior to the infection, and experienced at least one menstrual cycle after the infection. The 737 included participants were divided into mild and severe groups based on the severity of the infection. Deviations in first menstrual cycle post-infection were reported in 46.4% of participants (mild group 40.1% vs. severe group 55.2%, P<0.05). Menstrual changes were predominantly a late menstrual period (mild group 25.3% vs. severe group 30.4%), a shorter duration of menstrual flow (mild group 10.4% vs. severe group 14.7%), and a decrease in menstrual flow volume (mild group 16% vs. severe group 21.6%). Premenstrual syndrome symptoms in a small number of women were worse compared with pre-infection, especially in the severe group. During the second menstrual period after infection, most participants reported their menstrual characteristics had returned to those of pre-infection (mild group 88% vs. severe group 80.2%, P<0.05). In this investigation, SARS-CoV-2 infection had a substantial effect on women's menstrual characteristics, and the changes were mostly transient. Women with more severe COVID-19 symptoms experienced more significant changes. The potential long-term effects of SARS-CoV-2 on female reproductive health require further observation and research.

Cette étude visait à étudier les changements dans la menstruation et l'association entre la gravité d'Omicron et la menstruation après l'épidémie nationale de COVID-19 en Chine. Une étude transversale a adopté un questionnaire électronique pour mener une enquête anonyme en ligne. L'enquête visait les femmes en âge de procréer qui avaient été infectées par le SRAS-CoV-2, qui avaient leurs règles régulièrement au cours des six mois précédant l'infection et qui ont connu au moins un cycle menstruel après l'infection. Les 737 participants inclus ont été divisés en groupes légers et sévères en fonction de la gravité de l'infection. Des écarts dans le premier cycle menstruel post-infection ont été signalés chez 46,4 % des participantes (groupe léger 40,1 % contre groupe sévère 55,2 %, P <0,05). Les changements menstruels étaient principalement une période menstruelle tardive (groupe léger 25,3 % contre groupe sévère 30,4 %), une durée plus courte du flux menstruel (groupe léger 10,4 % contre groupe sévère 14,7 %) et une diminution du volume du flux menstruel (groupe léger). 16 % contre groupe sévère 21,6 %). Les symptômes du syndrome prémenstruel chez un petit nombre de femmes étaient pires que ceux observés avant l'infection, en particulier dans le groupe sévère. Au cours de la deuxième période menstruelle après l'infection, la plupart des participantes ont déclaré que leurs caractéristiques menstruelles étaient revenues à celles d'avant l'infection (groupe léger 88 % contre groupe sévère 80,2 %, P <0,05). Dans cette enquête, l'infection par le SRAS-CoV-2 a eu un effet substantiel sur les caractéristiques menstruelles des femmes, et les changements ont été pour la plupart transitoires. Les femmes présentant des symptômes plus graves de la COVID-19 ont connu des changements plus importants. Les effets potentiels à long terme du SRAS-CoV-2 sur la santé reproductive des femmes nécessitent des observations et des recherches plus approfondies.

Left atrial strain parameters to predicting elevated left atrial pressure in patients with atrial fibrillation.

OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Efficacy and Safety of Ganyushu Granule in Treatment of Premenstrual Syndrome with Gan (Liver) Depression and Qi Stagnation Syndrome: A Randomized, Double-Blind, Multi-Center, Phase-II Clinical Trial.

OBJECTIVE: To confirm the efficacy and safety of Ganyushu Granule (GYSG) in treating premenstrual syndrome (PMS) in patients with Gan (Liver) depression and qi stagnation syndrome (GDQSS) and determine its effective dosage. METHODS: From June 2018 to March 2021, a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization: high-dose GYSG group (n=78, GYSG 2 packs/time), low-dose GYSG group (n=82, GYSG and its simulant 1 pack/time), and placebo group (n=80, GYSG simulant 2 packs/time). Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles. Primary outcomes were PMS diary (PMSD) score and premenstrual tension syndrome self-rating scale (PMTS). Secondary outcomes were Chinese medicine (CM) syndrome efficacy. PMSD, PMTS, and efficacy of CM were evaluated with menstrual cycles during the treatment period. Outcome indicators were analyzed after each menstrual cycle. All analyses were performed using an intention-to-treat method, and clinical safety was assessed. RESULTS: Of the 216 patients included in the effectiveness analysis, 70, 75, and 71 patients were in the high-, low-dose GYSG, and placebo groups, respectively. From the 2nd treatment cycle, the change in PMSD scores in the high- and low-dose groups was lower than that in the placebo group (P<0.05). PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group (P<0.05), while after the 3rd treatment cycle, that in the low-dose group was lower than that in the placebo group (P<0.05). After the 2nd treatment cycle, the high-dose GYSG group had the best CM syndrome efficacy (P<0.05). No serious adverse reactions were reported. CONCLUSIONS: GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS. High-dose GYSG might be the optimal dose for a phase III trial. (Registration No. ChiCTR1800016595).

Zinc-Based ROS Amplifiers Trigger Cancer Chemodynamic/Ion Interference Therapy Through Self-Cascade Catalysis.

Nanozyme-mediated chemodynamic therapy has emerged as a promising strategy due to its tumor specificity and controlled catalytic activity. However, the poor efficacy caused by low hydrogen peroxide (H2O2) levels in the tumor microenvironment (TME) poses challenges. Herein, an H2O2 self-supplying nanozyme is constructed through loading peroxide-like active platinum nanoparticles (Pt NPs) on zinc peroxide (ZnO2) (denoted as ZnO2@Pt). ZnO2 releases H2O2 in response to the acidic TME. Pt NPs catalyze the hydroxyl radical generation from H2O2 while reducing the mitigation of oxidative stress by glutathione, serving as a reactive oxygen (ROS) amplifier through self-cascade catalysis. In addition, Zn2+ released from ZnO2 interferes with tumor cell energy supply and metabolism, enabling ion interference therapy to synergize with chemodynamic therapy. In vitro studies demonstrate that ZnO2@Pt induces cellular oxidative stress injury through enhanced ROS generation and Zn2+ release, downregulating ATP and NAD+ levels. In vivo assessment of anticancer effects showed that ZnO2@Pt could generate ROS at tumor sites to induce apoptosis and downregulate energy supply pathways associated with glycolysis, resulting in an 89.7% reduction in tumor cell growth. This study presents a TME-responsive nanozyme capable of H2O2 self-supply and ion interference therapy, providing a paradigm for tumor-specific nanozyme design.

Incidence and Influencing Factors of Anxiety and Depression in Individuals with Acute Ischemic Stroke: A Retrospective Study.

BACKGROUND: Acute ischemic stroke (AIS) is the most common type of stroke in clinical practice, and individuals with stroke are more prone to psychological disorders than healthy individuals. This study aims to explore the incidence of anxiety and depression and related influencing factors in individuals with AIS. METHODS: In brief, 680 individuals with AIS admitted to Chun'an County First People's Hospital from January 2021 to January 2023 were selected as the research subjects, and their clinical data were retrospectively analyzed. All patients were evaluated with the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) to observe the occurrence of anxiety and depression, and single-factor and multi-factor logistic regression were used to analyze the influencing factors of anxiety and depression. RESULTS: Among the 680 individuals with AIS, there were 63 cases of mild anxiety (9.26%), 25 cases of moderate anxiety (3.68%), and 8 cases of severe anxiety (1.18%), with a total of 96 cases (14.12%) with anxiety symptoms. Additionally, there were 74 cases of mild depression (10.88%), 28 cases of moderate depression (4.12%), and 10 cases of severe depression (1.47%), with a total of 112 cases with depression (16.47%). The results of univariate analysis showed that there was a weak correlation between age, body mass index, disease duration, marital status, and the development of anxiety and depression in individuals with AIS (p > 0.05). Educational level, underlying diseases, family income, and place of residence were found to influence the development of anxiety and depression in individuals with AIS (p < 0.05). The results of multivariate logistic regression analysis showed that educational level (no higher education), underlying diseases (with), family income (<50,000 yuan/year, the average exchange rate of RMB to USD was 6.7261), and place of residence (rural area) were influencing factors for the development of anxiety and depression in individuals with AIS (p < 0.05). CONCLUSION: Depression and anxiety are common psychological disorders in patients with AIS. The level of education (no higher education), underlying diseases (with), family income (<50,000 yuan/year), and place of residence (rural area) were risk factors that may lead to anxiety and depression in individuals with AIS. For those with risk factors for anxiety and depression, reasonable intervention should be continually provided to guide early disease prediction and treatment of anxiety and depression in individuals with AIS.

Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced acute thymus involution in mice via AMPK/Sirt1 pathway.

The thymus, a site to culture the naïve T lymphocytes, is susceptible to atrophy or involution due to aging, inflammation, and oxidation. Epigallocatechin-3-gallate (EGCG) has been proven to possess anti-inflammatory, antioxidant, and antitumor activity. Here, we investigate the effects of EGCG on thymic involution induced by lipopolysaccharide (LPS), an endotoxin derived from Gram-negative bacteria. The methodology included an in vivo experiment on female Kunming mice exposed to LPS and EGCG. Morphological assessment of thymic involution, immunohistochemical detection, and thymocyte subsets analysis by flow cytometry were further carried out to evaluate the potential role of EGCG on the thymus. As a result, we found that EGCG alleviated LPS-induced thymic atrophy, increased mitochondrial membrane potential and superoxide dismutase levels, and decreased malondialdehyde and reactive oxygen species levels. In addition, EGCG pre-supplement restored the ratio of thymocyte subsets, the expression of autoimmune regulator, sex-determining region Y-box 2, and Nanog homebox, and reduced the number of senescent cells and collagen fiber deposition. Western blotting results indicated that EGCG treatment elevated LPS-induced decrease in pAMPK, Sirt1 protein expression. Collectively, EGCG relieved thymus architecture and function damaged by LPS via regulation of AMPK/Sirt1 signaling pathway. Our findings may provide a new strategy on protection of thymus from involution caused by LPS by using EGCG. And EGCG might be considered as a potential agent for the prevention and treatment of thymic involution.

Lipid Nanoparticle-Mediated Delivery of CRISPR-Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism.

Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon-specific CRISPR-Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism-related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.

Evaluating the Causal Effects of Circulating Proteome on the Risk of Sepsis and Related Outcomes.

The current investigation deployed Mendelian randomization (MR) to elucidate the causal relationship between circulating proteins and sepsis. A rigorous two-sample MR analysis evaluated the effect of plasma proteins on the sepsis susceptibility. To affirm the integrity of MR findings, a suite of supplementary analyses, including Bayesian colocalization, Steiger filtering, the assessment of protein-altering polymorphisms, and the correlation between expression quantitative trait loci and protein quantitative trait loci (pQTLs), was employed. The study further integrated the examination of protein-protein interactions and pathway enrichment, along with the identification of pharmacologically actionable targets, to advance our comprehension and outline potential sepsis therapies. Subsequent analyses leveraging cis-pQTLs within MR studies unveiled noteworthy relationships: 94 specific proteins exhibited significant links with sepsis-related 28 day mortality, while 96 distinct proteins correlated with survival outcomes in sepsis. Furthermore, incorporating both cis- and trans-pQTLs in MR investigations revealed more comprehensive findings, associating 201 unique proteins with sepsis-related 28 day mortality and 199 distinct proteins with survival outcomes in sepsis. Markedly, colocalization analyses confirmed that eight of these proteins exhibited prominent evidence for colocalization, emphasizing their potential criticality in sepsis pathophysiology. Further in silico analyses were conducted to delineate putative regulatory networks and to highlight prospective drug targets among these proteins. Employing the MR methodology has shed light on plasma proteins implicated in the etiopathogenesis of sepsis. This novel approach unveiled numerous biomarkers and targets, providing a scientific rationale for the development of new therapeutic strategies and prophylactic measures against sepsis.

Postmortem Diffusion of Aconitum Alkaloids and Their Metabolites in Rabbits.

OBJECTIVES: To explore the postmortem diffusion rule of Aconitum alkaloids and their metabolites in poisoned rabbits, and to provide a reference for identifying the antemortem poisoning or postmortem poisoning of Aconitum alkaloids. METHODS: Twenty-four rabbits were sacrificed by tracheal clamps. After 1 hour, the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration. Then, they were placed supine and stored at 25 ℃. The biological samples from 3 randomly selected rabbits were collected including heart blood, peripheral blood, urine, heart, liver, spleen, lung and kidney tissues at 0 h, 4 h, 8 h, 12 h, 24 h, 48 h, 72 h and 96 h after intragastric administration, respectively. Aconitum alkaloids and their metabolites in the biological samples were analyzed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). RESULTS: At 4 h after intragastric administration, Aconitum alkaloids and their metabolites could be detected in heart blood, peripheral blood and major organs, and the contents of them changed dynamically with the preservation time. The contents of Aconitum alkaloids and their metabolites were higher in the spleen, liver and lung, especially in the spleen which was closer to the stomach. The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration. In contrast, the contents of Aconitum alkaloids and their metabolites in kidney were all lower. Aconitum alkaloids and their metabolites were not detected in urine. CONCLUSIONS: Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits, diffusing from high-content organs (stomach) to other major organs and tissues as well as the heart blood. The main mechanism is the dispersion along the concentration gradient, while urine is not affected by postmortem diffusion, which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Brachytherapy in craniopharyngiomas: a systematic review and meta-analysis of long-term follow-up.

OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.

Evaluation of a pleiotropic cytokinin polymorphism with cerebral infarction in a Chinese male population.

Cardiovascular diseases, particularly stroke, are a leading cause of morbidity and mortality worldwide. Genetic variations in genes associated with inflammation have been implicated in the pathogenesis of stroke. Interleukin-6 (IL-6), a pleiotropic cytokine with diverse biological functions, has been linked to cardiovascular diseases and stroke. The relationship between cerebral ischemia and inflammation is well-established, suggesting a potential role for IL-6 polymorphisms in stroke susceptibility. In the context of this study, the focus is on evaluating a pleiotropic cytokinin polymorphism, specifically IL-6-572GC, and its association with cerebral infarction in a Chinese male population. The investigation aims to elucidate the genetic correlation between IL-6 polymorphisms and stroke risk, particularly in the context of hemorrhagic subtype of stroke. The study utilizes a case-control design, comparing stroke patients with healthy controls while adjusting for classic risk factors associated with stroke. The methodology employed includes the detection of IL-6 polymorphisms using Real Time Taq Man Probe and PCR-RFLP methods. The results suggest an association between the IL-6-572GC genotype and an increased risk of stroke, particularly in the hemorrhagic subtype. However, the relationship between another IL-6 polymorphism, IL-6-174GC, and stroke remains inconclusive, except for a potential correlation with one allele. The findings underscore the potential role of IL-6-572GC genotype as a genetic risk factor for stroke in the Chinese male population under study. Further research involving larger cohorts is warranted to validate these results and clarify the role of IL-6-174GC polymorphism in stroke susceptibility. Understanding the genetic underpinnings of stroke can provide valuable insights for risk assessment and personalized treatment strategies in affected populations.

Locationally activated PRP via an injectable dual-network hydrogel for endometrial regeneration.

Enhancing the effectiveness of platelet-rich plasma (PRP) for endometrial regeneration is challenging, due to its limited mechanical properties and burst release of growth factors. Here, we proposed an injectable interpenetrating dual-network hydrogel that can locationally activate PRP within the uterine cavity, sustained release growth factors and further address the insufficient therapeutic efficacy. Locational activation of PRP is achieved using the dual-network hydrogel. The phenylboronic acid (PBA) modified methacrylated hyaluronic acid (HAMA) dispersion chelates Ca2+ by carboxy groups and polyphenol groups, and in situ crosslinked with PRP-loaded polyvinyl alcohol (PVA) dispersion by dynamic borate ester bonds thus establishing the soft hydrogel. Subsequently, in situ photo-crosslinking technology is employed to enhance the mechanical performance of hydrogels by initiating free radical polymerization of carbon-carbon double bonds to form a dense network. The PRP-hydrogel significantly promoted the endometrial cell proliferation, exhibited strong pro-angiogenic effects, and down-regulated the expression of collagen deposition genes by inhibiting the TGF-ß1-SMAD2/3 pathway in vitro. In vivo experiments using a rat intrauterine adhesion (IUA) model showed that the PRP-hydrogel significantly promoted endometrial regeneration and restored uterine functionality. Furthermore, rats treated with the PRP-hydrogel displayed an increase in the number of embryos, litter size, and birth rate, which was similar to normal rats. Overall, this injectable interpenetrating dual-network hydrogel, capable of locational activation of PRP, suggests a new therapeutic approach for endometrial repair.

Deep learning-based platform performs high detection sensitivity of intracranial aneurysms in 3D brain TOF-MRA: An external clinical validation study.

PURPOSE: To evaluate the diagnostic efficacy of a developed artificial intelligence (AI) platform incorporating deep learning algorithms for the automated detection of intracranial aneurysms in time-of-flight (TOF) magnetic resonance angiography (MRA). METHOD: This retrospective study encompassed 3D TOF MRA images acquired between January 2023 and June 2023, aiming to validate the presence of intracranial aneurysms via our developed AI platform. The manual segmentation results by experienced neuroradiologists served as the "gold standard". Following annotation of MRA images by neuroradiologists using InferScholar software, the AI platform conducted automatic segmentation of intracranial aneurysms. Various metrics including accuracy (ACC), balanced ACC, area under the curve (AUC), sensitivity (SE), specificity (SP), F1 score, Brier Score, and Net Benefit were utilized to evaluate the generalization of AI platform. Comparison of intracranial aneurysm identification performance was conducted between the AI platform and six radiologists with experience ranging from 3 to 12 years in interpreting MR images. Additionally, a comparative analysis was carried out between radiologists' detection performance based on independent visual diagnosis and AI-assisted diagnosis. Subgroup analyses were also performed based on the size and location of the aneurysms to explore factors impacting aneurysm detectability. RESULTS: 510 patients were enrolled including 215 patients (42.16 %) with intracranial aneurysms and 295 patients (57.84 %) without aneurysms. Compared with six radiologists, the AI platform showed competitive discrimination power (AUC, 0.96), acceptable calibration (Brier Score loss, 0.08), and clinical utility (Net Benefit, 86.96 %). The AI platform demonstrated superior performance in detecting aneurysms with an overall SE, SP, ACC, balanced ACC, and F1 score of 91.63 %, 92.20 %, 91.96 %, 91.92 %, and 90.57 % respectively, outperforming the detectability of the two resident radiologists. For subgroup analysis based on aneurysm size and location, we observed that the SE of the AI platform for identifying tiny (diameter＜3mm), small (3 mm ≤ diameter＜5mm), medium (5 mm ≤ diameter＜7mm) and large aneurysms (diameter ≥ 7 mm) was 87.80 %, 93.14 %, 95.45 %, and 100 %, respectively. Furthermore, the SE for detecting aneurysms in the anterior circulation was higher than that in the posterior circulation. Utilizing the AI assistance, six radiologists (i.e., two residents, two attendings and two professors) achieved statistically significant improvements in mean SE (residents: 71.40 % vs. 88.37 %; attendings: 82.79 % vs. 93.26 %; professors: 90.07 % vs. 97.44 %; P < 0.05) and ACC (residents: 85.29 % vs. 94.12 %; attendings: 91.76 % vs. 97.06 %; professors: 95.29 % vs. 98.82 %; P < 0.05) while no statistically significant change was observed in SP. Overall, radiologists' mean SE increased by 11.40 %, mean SP increased by 1.86 %, and mean ACC increased by 5.88 %, mean balanced ACC promoted by 6.63 %, mean F1 score grew by 7.89 %, and Net Benefit rose by 12.52 %, with a concurrent decrease in mean Brier score declined by 0.06. CONCLUSIONS: The deep learning algorithms implemented in the AI platform effectively detected intracranial aneurysms on TOF-MRA and notably enhanced the diagnostic capabilities of radiologists. This indicates that the AI-based auxiliary diagnosis model can provide dependable and precise prediction to improve the diagnostic capacity of radiologists.

Efficacy of endometrial receptivity testing for recurrent implantation failure in patients with euploid embryo transfers: study protocol for a randomized controlled trial.

BACKGROUND: Embryo implantation remains a critical barrier in assisted reproductive technologies. One of the main causes of unsuccessful embryo implantation is window of implantation (WOI) displacement, particularly in patients with recurrent implantation failure (RIF). Therefore, a reliable diagnostic tool for identifying the optimal WOI is essential. Previous data has suggested that a novel RNA-Seq-based endometrial receptivity testing (ERT) can diagnose WOI, guide personalized embryo transfer (pET), and improve pregnancy outcomes in patients with RIF compared to standard embryo transfer (sET). However, there is still a lack of evidence from randomized controlled trials (RCT) with sufficient power to determine whether pET based on ERT can increase the rate of live births as the primary outcome. METHODS: This trial is a prospective, single-blind, parallel-group RCT (1:1 ratio of pET versus sET). Infertile women with RIF who intend to undergo frozen-thawed embryo transfer (FET) after preimplantation genetic testing for aneuploidy (PGT-A) with the availability of at least one euploid blastocyst for transfer will be enrolled and assigned into two parallel groups randomly. Participants in the intervention group will undergo ERT and then pET based on the results of ERT, while those in the control group will undergo sET. The primary outcome is live birth rate. DISCUSSION: The findings of this study will provide evidence for the effect of pET guided by ERT on pregnancy outcomes in patients with RIF. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100049041. Registered on 20 July 2021.

Interleukin-17A in diabetic retinopathy: The crosstalk of inflammation and angiogenesis.

Diabetic retinopathy (DR) is a severe ocular complication of diabetes which can leads to irreversible vision loss in its late-stage. Chronic inflammation results from long-term hyperglycemia contributes to the pathogenesis and progression of DR. In recent years, the interleukin-17 (IL-17) family have attracted the interest of researchers. IL-17A is the most widely explored cytokine in IL-17 family, involved in various acute and chronic inflammatory diseases. Growing body of evidence indicate the role of IL-17A in the pathogenesis of DR. However, the pro-inflammatory and pro-angiogenic effect of IL-17A in DR have not hitherto been reviewed. Gaining an understanding of the pro-inflammatory role of IL-17A, and how IL-17A control/impact angiogenesis pathways in the eye will deepen our understanding of how IL-17A contributes to DR pathogenesis. Herein, we aimed to thoroughly review the pro-inflammatory role of IL-17A in DR, with focus in how IL-17A impact inflammation and angiogenesis crosstalk.

Relationship Between the Gut Microbiota and Neurological Deficits in Patients With Cerebral Ischemic Stroke.

OBJECTIVE: The aim of the paper was to investigate the composition and structure of intestinal flora in patients with cerebral ischemic stroke (CIS), and to investigate the relationship between gut microbiota (GM) and different levels of stroke severity. METHODS: In this study, 47 CIS patients (16 mild, 21 moderate, and 10 severe) and 15 healthy controls were included. General information, clinical data, and behavioral scores of the enrolled subjects were collected. Deoxyribonucleic acid in fecal intestinal flora was extracted and detected using high-throughput Illumina 16S ribosomal ribonucleic acid sequencing technology. Finally, the correlation between the community composition of intestinal microbiota and National Institutes of Health Stroke Scale (NIHSS) score in CIS patients was analyzed. RESULTS: Compared with healthy controls, there was no statistically significant difference in Alpha diversity among CIS patients, but the principal coordinate analysis showed significant differences in the composition of the GM among stroke patients with different degrees of severity and controls. In CIS patients, Streptococcus was significantly enriched, and Eshibacter-Shigella, Bacteroides, and Agathobacter were significantly down-regulated (P < .05). In addition, the relative abundance of Blautia was negatively correlated with the NIHSS score. CONCLUSIONS: Our results show that different degrees of CIS severity exert distinct effects on the intestinal microbiome. This study reveals the intestinal microecological changes after brain injury from the perspective of brain-gut axis. Intestinal microorganisms not only reveal the possible pathological process and indicate the severity of neurologic impairment, but also make targeted therapy possible for CIS patients.

Hypoxia predicts favorable response to carbon ion radiotherapy in non-small cell lung cancer (NSCLC) defined by 18F-FMISO positron emission tomography/computed tomography (PET/CT) imaging.

Background: Hypoxia is the bottleneck that affects the response of conventional photon radiotherapy, but it does not seem to have much effect on carbon ion radiotherapy (CIRT). This study aimed to evaluate the changes of hypoxia before and after CIRT in patients with non-small cell lung cancer (NSCLC) and whether 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) imaging could predict the response to CIRT in NSCLC patients. Methods: A total of 29 patients with NSCLC who received CIRT were retrospectively included. 18F-FMISO PET/CT imaging was performed before and after treatment, and chest CT was performed after radiotherapy. Radiation response within 1 week after radiotherapy and at the initial follow-up were defined as the immediate response (IR) and early response (ER), respectively. The tumor-to-muscle ratio (TMR), hypoxia volume (HV), and the ΔTMR and ΔHV values of 18F-FMISO uptake were collected. Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and binary logistic regression were used to analyze data. Results: (I) Baseline TMR could predict the IR to CIRT with a baseline TMR cut-off value of 2.35, an area under the curve (AUC) of 0.85 [95% confidence interval (CI): 0.62-1.00], a sensitivity of 80.0%, a specificity of 87.5%, and an accuracy of 85.7%. Taking the baseline TMR =2.35 as the cut-off value of high-hypoxia and low-hypoxia group, the IR rate of the high-hypoxia group [66.7% (4/6)] and the low-hypoxia group [6.7% (1/15)] was statistically different (P=0.01). (II) ΔTMR could predict early treatment response after CIRT at initial follow-up, with a cut-off value of ΔTMR =36.6%, AUC of 0.80 (95% CI: 0.61-1.00), sensitivity of 72.7%, specificity of 90.0% and accuracy of 71.4%. Conclusions: A higher degree of tumor hypoxia may be associated with a better IR to CIRT. ΔTMR could predict early treatment response after CIRT.