Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Alleviating tiling effect by random walk sliding window in high-resolution histological whole slide image synthesis.

Multiplex immunofluorescence (MxIF) is an advanced molecular imaging technique that can simultaneously provide biologists with multiple (i.e., more than 20) molecular markers on a single histological tissue section. Unfortunately, due to imaging restrictions, the more routinely used hematoxylin and eosin (H&E) stain is typically unavailable with MxIF on the same tissue section. As biological H&E staining is not feasible, previous efforts have been made to obtain H&E whole slide image (WSI) from MxIF via deep learning empowered virtual staining. However, the tiling effect is a long-lasting problem in high-resolution WSI-wise synthesis. The MxIF to H&E synthesis is no exception. Limited by computational resources, the cross-stain image synthesis is typically performed at the patch-level. Thus, discontinuous intensities might be visually identified along with the patch boundaries assembling all individual patches back to a WSI. In this work, we propose a deep learning based unpaired high-resolution image synthesis method to obtain virtual H&E WSIs from MxIF WSIs (each with 27 markers/stains) with reduced tiling effects. Briefly, we first extend the CycleGAN framework by adding simultaneous nuclei and mucin segmentation supervision as spatial constraints. Then, we introduce a random walk sliding window shifting strategy during the optimized inference stage, to alleviate the tiling effects. The validation results show that our spatially constrained synthesis method achieves a 56% performance gain for the downstream cell segmentation task. The proposed inference method reduces the tiling effects by using 50% fewer computation resources without compromising performance. The proposed random sliding window inference method is a plug-and-play module, which can be generalized for other high-resolution WSI image synthesis applications. The source code with our proposed model are available at https://github.com/MASILab/RandomWalkSlidingWindow.git.

Tilianin enhances the antitumor effect of sufentanil on non-small cell lung cancer.

Non-small cell cancer (NSCLC) is the most common cancer in the world, but its effective therapeutic methods are limited. Tilianin and sufentanil alleviate various human tumors. This research aimed to clarify the functions and mechanisms of Tilianin and sufentanil in NSCLC. The functions of Tilianin and sufentanil on NSCLC cell viability, apoptosis, mitochondrial dysfunction, and immunity in vitro were examined using Cell Counting Kit-8 assay, flow cytometry, reactive oxygen species level analysis, CD8+ T cell percentage analysis, Western blot, and enzyme-linked immunosorbent assay, respectively. The molecular mechanism regulated by Tilianin and sufentanil in NSCLC was assessed using Western blot, and immunofluorescence assays. Meanwhile, the roles of Tilianin and sufentanil in NSCLC tumor growth, apoptosis, and immunity in vivo were determined by establishing a tumor xenograft mouse model, immunohistochemistry, and Western blot assays. When sufentanil concentration was proximity 2 nM, the inhibition rate of NSCLC cell viability was 50%. The IC50 for A549 cells was 2.36 nM, and the IC50 for H1299 cells was 2.18 nM. The IC50 of Tilianin for A549 cells was 38.7 µM, and the IC50 of Tilianin for H1299 cells was 44.6 µM. Functionally, 0.5 nM sufentanil and 10 µM Tilianin reduced NSCLC cell (A549 and H1299) viability in a dose-dependent manner. Also, 0.5 nM sufentanil and 10 µM Tilianin enhanced NSCLC cell apoptosis, yet this impact was strengthened after a combination of Tilianin and Sufentanil. Furthermore, 0.5 nM sufentanil and 10 µM Tilianin repressed NSCLC cell mitochondrial dysfunction and immunity, and these impacts were enhanced after a combination of Tilianin and Sufentanil. Mechanistically, 0.5 nM sufentanil and 10 µM Tilianin repressed the NF-κB pathway in NSCLC cells, while this repression was strengthened after a combination of Tilianin and Sufentanil. In vivo experimental data further clarified that 1 µg/kg sufentanil and 10 mg/kg Tilianin reduced NSCLC growth, immunity, and NF-κB pathway-related protein levels, yet these trends were enhanced after a combination of Tilianin and Sufentanil. Tilianin strengthened the antitumor effect of sufentanil in NSCLC.

N-methyl-D-aspartate Receptor Subunits 2A and 2B Mediate Connexins and Pannexins in the Trigeminal Ganglion Involved in Orofacial Inflammatory Allodynia during Temporomandibular Joint Inflammation.

Temporomandibular joint osteoarthritis (TMJOA) is a severe form of temporomandibular joint disorders (TMD), and orofacial inflammatory allodynia is one of its common symptoms which lacks effective treatment. N-methyl-D-aspartate receptor (NMDAR), particularly its subtypes GluN2A and GluN2B, along with gap junctions (GJs), are key players in the mediation of inflammatory pain. However, the precise regulatory mechanisms of GluN2A, GluN2B, and GJs in orofacial inflammatory allodynia during TMJ inflammation still remain unclear. Here, we established the TMJ inflammation model by injecting Complete Freund's adjuvant (CFA) into the TMJ and used Cre/loxp site-specific recombination system to conditionally knock out (CKO) GluN2A and GluN2B in the trigeminal ganglion (TG). Von-frey test results indicated that CFA-induced mechanical allodynia in the TMJ region was relieved in GluN2A and GluN2B deficient mice. In vivo, CFA significantly up-regulated the expression of GluN2A and GluN2B, Gjb1, Gjb2, Gjc2 and Panx3 in the TG, and GluN2A and GluN2B CKO played different roles in mediating the expression of Gjb1, Gjb2, Gjc2 and Panx3. In vitro, NMDA up-regulated the expression of Gjb1, Gjb2, Gjc2 and Panx3 in satellite glial cells (SGCs) as well as promoted the intercellular communication between SGCs, and GluN2A and GluN2B knocking down (KD) altered the expression and function differently. NMDAR regulated Gjb1 and Panx3 through ERK1/2 pathway, and mediated Gjb2 and Gjc2 through MAPK, PKA, and PKC intracellular signaling pathways. These findings shed light on the distinct functions of GluN2A and GluN2B in mediating peripheral sensitization induced by TMJ inflammation in the TG, offering potential therapeutic targets for managing orofacial inflammatory allodynia.

Percutaneous Approaches to Hypoglossal Nerve Stimulation: A Pilot Study During Drug-Induced Sleep Endoscopy.

Hypoglossal nerve stimulation (HNS) is a surgical treatment option for select patients with obstructive sleep apnea that currently requires intraoperative dissection of the hypoglossal nerve (HGN) for implantation of an electrode array. Most HNS strategies target select HGN protrusor muscle branches and exclude undesirable retractor branches. We hypothesized that the target HGN branches could instead be selectively stimulated with a percutaneously delivered electrode array under ultrasound guidance via several anatomic approaches. Five different anatomic approaches were iteratively developed and evaluated during drug-induced sleep endoscopy across 14 patients: posterior, intraoral, anteromedial, anterolateral, and paracoronal. The paracoronal and anterolateral approaches were the most successful, with comparable changes in pharyngeal critical closing and opening pressures. Our data suggest that percutaneous delivery of an HGN electrode is feasible and may decrease the morbidity of HNS therapy implantation. Further work is necessary to ascertain what anatomic approach is optimal for percutaneous electrode delivery.

Modification effects of immigration status and comorbidities on associations of heat and heatwave with stroke morbidity.

BACKGROUND: Heat and heatwave have been associated with stroke morbidity, but it is still unclear whether immigrants from different geographic regions and patients with comorbidity are more vulnerable to heat and heatwave. METHODS: Time-stratified case-crossover design combined with generalized additive quasi-Poisson models were used to quantify the relative risks (RR) of heat and heatwave on first-ever stroke morbidity during 0-7 lag days. Attributable fractions (AF) were estimated to assess the first-ever stroke morbidity burden due to heat and heatwave. Stratified analyses for sex, age, disease subtypes, resident characteristics, and comorbidity type were performed to identify potential modification effects. RESULTS: Heat and heatwave were associated with first-ever stroke morbidity, with the AF of 2.535% (95% eCI: 0.748, 4.205) and 2.409% (95% CI: 1.228, 3.400), respectively. Among northern and southern immigrants, the AF for heat was 2.806% (0.031, 5.069) and 2.798% (0.757, 4.428), respectively, and the AF for heatwave was 2.918% (0.561, 4.618) and 2.387% (1.174, 3.398), respectively, but the effects of both on natives were statistically insignificant. Among patients with hypertension, dyslipidemia, or diabetes, the AF for heat was 3.318% (1.225, 5.007), 4.237% (1.037, 6.770), and 4.860% (1.171, 7.827), respectively, and the AF for heatwave was 2.960% (1.701, 3.993), 2.771% (0.704, 4.308), and 2.652% (0.653, 4.185), respectively. However, the effects of both on patients without comorbidity were statistically insignificant. CONCLUSION: Heat and heatwave are associated with an increased risk of first-ever stroke morbidity among immigrants and those with comorbid hypertension, dyslipidemia, or diabetes, with the effects primarily due to non-native individuals.

Insulin resistance, coronary artery lesion complexity and adverse cardiovascular outcomes in patients with acute coronary syndrome.

BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.

Machine learning to predict the occurrence of thyroid nodules: towards a quantitative approach for judicious utilization of thyroid ultrasonography.

Introduction: Ultrasound is instrumental in the early detection of thyroid nodules, which is crucial for appropriate management and favorable outcomes. However, there is a lack of clinical guidelines for the judicious use of thyroid ultrasonography in routine screening. Machine learning (ML) has been increasingly used on big data to predict clinical outcomes. This study aims to leverage the ML approach in assessing the risk of thyroid nodules based on common clinical features. Methods: Data were sourced from a Chinese cohort undergoing routine physical examinations including thyroid ultrasonography between 2013 and 2023. Models were established to predict the 3-year risk of thyroid nodules based on patients' baseline characteristics and laboratory tests. Four ML algorithms, including logistic regression, random forest, extreme gradient boosting, and light gradient boosting machine, were trained and tested using fivefold cross-validation. The importance of each feature was measured by the permutation score. A nomogram was established to facilitate risk assessment in the clinical settings. Results: The final dataset comprised 4,386 eligible subjects. Thyroid nodules were detected in 54.8% (n=2,404) individuals within the 3-year observation period. All ML models significantly outperformed the baseline regression model, successfully predicting the occurrence of thyroid nodules in approximately two-thirds of individuals. Age, high-density lipoprotein, fasting blood glucose and creatinine levels exhibited the highest impact on the outcome in these models. The nomogram showed consistency and validity, providing greater net benefits for clinical decision-making than other strategies. Conclusion: This study demonstrates the viability of an ML-based approach in predicting the occurrence of thyroid nodules. The findings highlight the potential of ML models in identifying high-risk individuals for personalized screening, thereby guiding the judicious use of ultrasound in this context.

What is hindering Chinese women from participating in combat sports?

With the awakening of female consciousness, women's participation in sports has gradually gained autonomy and agency. However, Chinese women still face numerous restrictions in combat sports, hindering the development of this industry. Based on years of practice and research experience in the field, we summarize some general and specific issues, such as stigmatization and the constraints of traditional Chinese thinking. These issues need attention and consideration in the pursuit of gender equality in sports in the future.

Comparison of the effectiveness of probiotic supplementation in glucose metabolism, lipid profile, inflammation and oxidative stress in pregnant women.

Objective: The optimal probiotic supplementation in pregnant women has not been thoroughly evaluated. By employing a network meta-analysis (NMA) approach, we compared the effectiveness of different probiotic supplementation strategies for pregnant women. Methods: A comprehensive search across multiple databases was performed to identify studies comparing the efficacy of probiotic supplements with each other or the control (placebo) among pregnant women. Results: This NMA, including 32 studies, systematically evaluated 6 probiotic supplement strategies: Lactobacillus, Lacticaseibacillus rhamnosus and Bifidobacterium (LRB), Lactobacillus acidophilus and Bifidobacterium (LABB), Lactobacillus acidophilus, Lacticaseibacillus casei, and Bifidobacterium bifidum (LLB), multi-combination of four probiotics (MP1), and multi-combination of six or more probiotics (MP2). Among these strategies, LLB, MP1, and MP2 all contain LABB. The NMA findings showed that MP1 was the most effective in reducing fasting blood sugar (FBS) (surface under the cumulative ranking curve [SUCRA]: 80.5%). In addition, MP2 was the most efficacious in lowering the homeostasis model assessment of insulin resistance (HOMA-IR) (SUCRA: 89.1%). LABB was ranked as the most effective in decreasing low-density lipoprotein cholesterol (LDLC) (SUCRA: 95.5%), total cholesterol (TC) (SUCRA: 95.5%), and high-sensitivity C-reactive protein (hs-CRP) (SUCRA: 94.8%). Moreover, LLB was ranked as the most effective in raising total antioxidant capacity (TAC) (SUCRA: 98.5%). Conclusion: Multi-combination of probiotic strains, especially those strategies containing LABB, may be more effective than a single probiotic strain in glycolipid metabolism, inflammation, and oxidative stress of pregnant women.

Thermophoretic glycan profiling of extracellular vesicles for triple-negative breast cancer management.

Triple-negative breast cancer (TNBC) is a highly metastatic and heterogeneous type of breast cancer with poor outcomes. Precise, non-invasive methods for diagnosis, monitoring and prognosis of TNBC are particularly challenging due to a paucity of TNBC biomarkers. Glycans on extracellular vesicles (EVs) hold the promise as valuable biomarkers, but conventional methods for glycan analysis are not feasible in clinical practice. Here, we report that a lectin-based thermophoretic assay (EVLET) streamlines vibrating membrane filtration (VMF) and thermophoretic amplification, allowing for rapid, sensitive, selective and cost-effective EV glycan profiling in TNBC plasma. A pilot cohort study shows that the EV glycan signature reaches 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of TNBC therapeutic response. Moreover, we demonstrate the potential of EV glycan signature for predicting TNBC progression. Our EVLET system lays the foundation for non-invasive cancer management by EV glycans.

LncRNA Anxa10-203 enhances Mc1r mRNA stability to promote neuropathic pain by recruiting DHX30 in the trigeminal ganglion.

BACKGROUND: Trigeminal nerve injury is one of the most serious complications in oral clinics, and the subsequent chronic orofacial pain is a consumptive disease. Increasing evidence demonstrates long non-coding RNAs (lncRNAs) play an important role in the pathological process of neuropathic pain. This study aims to explore the function and mechanism of LncRNA Anxa10-203 in the development of orofacial neuropathic pain. METHODS: A mouse model of orofacial neuropathic pain was established by chronic constriction injury of the infraorbital nerve (CCI-ION). The Von Frey test was applied to evaluate hypersensitivity of mice. RT-qPCR and/or Western Blot were performed to analyze the expression of Anxa10-203, DHX30, and MC1R. Cellular localization of target genes was verified by immunofluorescence and RNA fluorescence in situ hybridization. RNA pull-down and RNA immunoprecipitation were used to detect the interaction between the target molecules. Electrophysiology was employed to assess the intrinsic excitability of TG neurons (TGNs) in vitro. RESULTS: Anxa10-203 was upregulated in the TG of CCI-ION mice, and knockdown of Anxa10-203 relieved neuropathic pain. Structurally, Anxa10-203 was located in the cytoplasm of TGNs. Mechanistically, Mc1r expression was positively correlated with Anxa10-203 and was identified as the functional target of Anxa10-203. Besides, Anxa10-203 recruited RNA binding protein DHX30 and formed the Anxa10-203/DHX30 complex to enhance the stability of Mc1r mRNA, resulting in the upregulation of MC1R, which contributed to the enhancement of the intrinsic activity of TGNs in vitro and orofacial neuropathic pain in vivo. CONCLUSIONS: LncRNA Anxa10-203 in the TG played an important role in orofacial neuropathic pain and mediated mechanical allodynia in CCI-ION mice by binding with DHX30 to upregulate MC1R expression.

A historical controlled study of domestic trastuzumab and pertuzumab in combination with docetaxel for the neoadjuvant treatment of early HER2-positive breast cancer.

Background: HER2-positive molecular breast cancer subtypes are characterized by high aggressiveness and malignancy, and their metastasis and mortality rates are among the highest of all types of breast cancer. The use of anti-HER2-targeted agents in neoadjuvant therapy has significantly improved the prognosis of patients with HER2-positive breast cancer. In this study, we investigated the efficacy and safety of a neoadjuvant Chinese THP regimen (docetaxel, trastuzumab biosimilar TQB211 plus the pertuzumab biosimilar TQB2440 or pertuzumab) for ER/PR-negative and HER2-positive breast cancer in China. Method: All enrolled patients received the THP regimen (T: docetaxel 75 mg/m2 per cycle; H: trastuzumab biosimilar TQB211 8 mg/kg in the first cycle and 6 mg/kg maintenance dose in cycles 2 to 4; P: pertuzumab biosimilar TQB2440 or pertuzumab 840 mg in the first cycle, maintenance dose 420 mg in cycles 2 to 4) every 3 weeks for 4 cycles. The biosimilar TQB2440 pertuzumab and pertuzumab were randomly assigned to patients. Docetaxel, TQB211, and TQB2440 were all developed by Chiatai Tianqing. The primary endpoint was the complete pathological response (pCR) in the breast, and the secondary endpoint was cardiac safety. Results: Of the 28 eligible patients, 19 (67.9%) achieved tpCR. The tpCR rate was higher than in the NeoSphere trial (pCR63.2%) and the PEONY study (tpCR52.5%). The adverse events that occurred most frequently were leukopenia and neutropenia, with incidence rates of 82.1% and 75.0%, respectively. Of these, grade 3 leukopenia and neutropenia occupied 46.4% and 35.7%. Other grade 3 or higher adverse events were bone marrow suppression (7.1%), lymphopenia (3.6%), and anemia (3.6%). There were no events of heart failure in patients and no patient died during the neoadjuvant phase. Conclusion: Domestic dual-target HP has a more satisfactory efficacy and safety in the neoadjuvant phase of treatment. Clinical trial registration: https://clinicaltrials.gov/study/NCT05985187, NCT05985187.

Bidirectional modification effects on nonlinear associations of summer temperature and air pollution with first-ever stroke morbidity.

High temperature and air pollution may induce stroke morbidity. However, whether associations between high temperature and air pollution with stroke morbidity are modified by each other is still unclear. Data on 23,578 first-ever stroke patients in Shenzhen, China, during the summers of 2014-2018 were collected. Distributed lag nonlinear models were used to assess the modifying effects of air pollution stratified by the median for the associations between summer temperature and stroke morbidity at 0-3 lag days; modifying effects of temperature stratified by the minimum morbidity temperature on the associations between air pollution and stroke morbidity at the same lags were also estimated. The attributable risks of high temperature and high pollution on stroke morbidity were quantified. Stratified analyses of gender, age, migration type, and complication type were conducted to assess vulnerable population characteristics. Summer high temperature may induce stroke morbidity at high-level PM2.5, PM10, O3, SO2, and NO2 conditions, with attributable fraction (AF) of 2.982% (95% empirical confidence interval [eCI]: 0.943, 4.929), 3.113% (0.948, 5.200), 2.841% (0.943, 4.620), 3.617% (1.539, 5.470), and 2.048% (0.279, 3.637), respectively. High-temperature effects were statistically insignificant at corresponding low-level air pollution conditions. High-level PM2.5, PM10, and O3 may induce stroke morbidity at high-temperature conditions, with AF of 3.664% (0.036, 7.196), 4.129% (0.076, 7.963), and 4.574% (1.009, 7.762), respectively. High-level PM2.5, PM10, and O3 were not associated with stroke morbidity at low-temperature conditions. The effects of high temperature and high pollution on stroke morbidity were statistically significant among immigrants and patients with hypertension, dyslipidemia, or diabetes but insignificant among natives and patients without complications. The associations of summer temperature and air pollution with first-ever stroke morbidity may be enhanced bidirectionally. Publicity on the health risks of combined high temperature and high pollution events should be strengthened to raise protection awareness of relevant vulnerable populations.

Blood Group Antigen A Carriers Exhibit an Extended Progression-Free Survival with no more Immune-Related Adverse Events.

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression-free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98). The association results from the SNP-derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non-antigen A carriers (HR = 0.61, 95% CI = 0.40-0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44-0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune-related adverse events (irAEs) or organ-specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy.

On-Demand 3D Spatial Distribution of Magnetic Permeability Based on Fe3 O4 Nanoparticle Liquid Toward Micro-Cavity Detectors.

The change of 3D spatial distribution of magnetic permeability can lead to the generation of introduced electrical signals. However, present studies can only achieve rough regulation by simple shape deformation of magnetic elastomers such as compression, bending, or stretching. Accurate control of the 3D spatial distribution of magnetic permeability is still an open question. In this study, an on-demand 3D spatial distribution of magnetic permeability by controlled flowing of Fe3 O4 nanoparticle liquid (FNL) is demonstrated. The flowing routes of FNL are tuned by a 3D-printed cage with pre-designed hollow structure, thus changing the 3D spatial distribution of magnetic permeability. Then, eight symmetrically distributed coils under cage are used to receive characteristic induction voltage signals. Maxwell numerical simulation reveals the working mechanism of signal generation. Notably, those eight coils can detect FNL flowing status in eight directions, allowing recognition of up to 255 different FNL flowing combinations. By introducing machine learning, the micro-cavity detector based on FNL can distinguish nine kinds of micro-cavity structures with an accuracy of 98.77%. This work provides a new strategy for the adjustment of the 3D spatial distribution of the magnetic permeability and expands the application of FNL in the field of space exploration.

Canada acute coronary syndrome risk score predicts no-/slow-reflow in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Background: The no-/slow-reflow phenomenon following primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI)is associated with poor prognosis. The early identification of high-risk patients with no-/slow-reflow is critical. This study aimed to evaluate the predictive ability of the Canada Acute Coronary Syndrome (C-ACS) risk score for no-/slow-reflow in these patients. Methods: Patients with STEMI who underwent primary PCI were consecutively enrolled and divided into three groups based on their C-ACS scores: 0, 1, and ≥2. The C-ACS score was computed using the four clinical variables evaluated at admission (one point for each): age ≥75 years, heart rate >100 beats/min, systolic blood pressure <100 mmHg, and Killip class >1. No-/slow-reflow was defined as thrombolysis in a myocardial infarction flow grade of 0-2 after primary PCI. The predictive ability of the C-ACS score for no-/slow-reflow was evaluated using a receiver operating characteristic curve. Results: A total of 834 patients were enrolled, of whom 109 (13.1 %) developed no-/slow-reflow. The incidence of no-/slow-reflow increased from the C-ACS 0 group to the C-ACS ≥2 group (6.1 % vs 17.7 % vs 34.3 %, respectively, p < 0.001). After multivariable adjustment, the C-ACS score was an independent predictor of no-/slow-reflow (odd ratio 2.623, 95 % confidence interval 1.948-3.532, p < 0.001). Furthermore, the C-ACS score showed good discrimination for no-/slow-reflow (area under the curve 0.707, 95 % confidence interval 0.653-0.762, p < 0.001). Further subgroup analyses indicated a significant interaction between the C-ACS score and patient sex (p for interaction = 0.011). The independent association between the C-ACS score and no-/slow-reflow was only observed in male patients (odd ratio 3.061, 95 % confidence interval 1.931-4.852, p < 0.001). During a median follow-up duration of 4.3 years, the C-ACS score was independently associated with major adverse cardiovascular events independent of the occurrence of no-/slow-reflow (p for interaction = 0.212). Conclusion: The C-ACS risk score could independently predict the no-/slow-reflow in patients with STEMI undergoing primary PCI, particularly in male patients.

Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study.

BACKGROUND: Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score. METHODS: This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality. RESULTS: After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48-2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64-2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90-3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes. CONCLUSIONS: In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.

The triglyceride-glucose index predicts 1-year major adverse cardiovascular events in end-stage renal disease patients with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index has been suggested as a dependable indicator for predicting major adverse cardiovascular events (MACE) in individuals with cardiovascular conditions. Nevertheless, there is insufficient data on the predictive significance of the TyG index in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). METHODS: This study, conducted at multiple centers in China, included 959 patients diagnosed with dialysis and CAD from January 2015 to June 2021. Based on the TyG index, the participants were categorized into three distinct groups. The study's primary endpoint was the combination of MACE occurring within one year of follow-up, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. We assessed the association between the TyG index and MACE using Cox proportional hazard models and restricted cubic spline analysis. The TyG index value was evaluated for prediction incrementally using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The three groups showed notable variations in the risk of MACE (16.3% in tertile 1, 23.5% in tertile 2, and 27.2% in tertile 3; log-rank P = 0.003). Following complete adjustment, patients with the highest TyG index exhibited a notably elevated risk of MACE in comparison to those in the lowest tertile (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.14-2.35, P = 0.007). Likewise, each unit increase in the TyG index correlated with a 1.37-fold higher risk of MACE (HR 1.37, 95% CI 1.13-1.66, P = 0.001). Restricted cubic spline analysis revealed a connection between the TyG index and MACE (P for nonlinearity > 0.05). Furthermore, incorporating the TyG index to the Global Registry of Acute Coronary Events risk score or baseline risk model with fully adjusted factors considerably enhanced the forecast of MACE, as demonstrated by the C-statistic, continuous NRI, and IDI. CONCLUSIONS: The TyG index might serve as a valuable and dependable indicator of MACE risk in individuals with dialysis and CAD, indicating its potential significance in enhancing risk categorization in clinical settings.

Association of triglyceride-glucose index with coronary severity and mortality in patients on dialysis with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is validated as a reliable biomarker of insulin resistance and an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients on dialysis with coronary artery disease (CAD) remained unexplored. This study aimed to determine the association between the TyG index and CAD severity and mortality in these patients. METHODS: A total of 1061 dialysis patients with CAD were enrolled in this multi-center cohort study from January 2015 to June 2021. The extent and severity of CAD were evaluated using the multivessel disease and Gensini score (GS). Patients were followed up for all-cause death and cardiovascular death. RESULTS: The multivariable logistic regression model indicated that the TyG index was significantly associated with multivessel disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.18-1.94, P = 0.001), and high GS (OR 1.33, 95% CI 1.10-1.61, P = 0.003). After adjusting for baseline risk factors, the hazards of all-cause death and cardiovascular death were 1.23 (95% CI 1.06-1.43, P = 0.007), and 1.33 (95% CI 1.11-1.59, P = 0.002), independent of CAD severity. Restricted cubic spline analysis identified a dose-response association between the TyG index and both CAD severity and mortality (all P for nonlinearity > 0.05). When modeling the TyG index as a categorical variable, these independent associations remained. Subgroup analyses did not substantially modify the results. Furthermore, incorporating the TyG index into the existing risk prediction model improved the predictive accuracy for all-cause death and cardiovascular death, as evaluated by C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In patients on dialysis with CAD, the TyG index was significantly associated with more severe CAD as well as mortality. These results highlight the clinical importance of the TyG index for assessing CAD severity and risk stratification in patients on dialysis with CAD.