Search

Background: Thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder. The occurrence of TTP subsequent to an emergent aortic valve replacement after a TAVR procedure is exceedingly uncommon with only a few reported cases worldwide., Case Presentation: We report the case of a 70-year-old female patient diagnosed with aortic insufficiency. Following a transcatheter aortic valve replacement, she underwent emergency aortic valve replacement under cardiopulmonary bypass on the subsequent day due to heart valve displacement. The postoperative diagnosis revealed TTP and symptomatic treatment involving plasma exchange was administered. After demonstrating steady improvement, the patient was eventually discharged., Conclusion: Aortic valve replacement after TAVR is a high-risk procedure and increases susceptibility for developing secondary TTP. The diagnosis and treatment of secondary TPP is considerably challenging, and early diagnosis with symptomatic treatment including plasma exchange can increase patient survival., (© 2024. The Author(s).)

Objectives: This study aimed to evaluate the association between different levels of physical activity and risk of developing type 2 diabetes (T2D) mellitus among adults with prediabetes in Chinese population., Methods: This prospective population-based cohort study included 12,424 participants (mean [SD] age, 52.8 [16.8] years; 82.2% men) with prediabetes at 2014 survey of the Kailuan study. Physical activity information was collected through the International Physical Activity Questionnaire-Short Form and categorized by metabolic equivalent (MET) of task as low, moderate, and high. Cox regression models were built to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between physical activity levels and incident T2D., Results: During a median follow-up of 3.6 years, 2,207 (17.8%) participants developed T2D. The incident rate of T2D were 55.83/1000, 35.14/1000, and 39.61/1000 person-years in the low, moderate, and high physical activity level group, respectively. Both moderate (HR 0.57, 95% CI 0.49 to 0.67) and high (HR 0.76, 95% CI 0.66 to 0.89) physical activity levels were associated with lower risks of developing T2D compared to low physical activity level (P for trend < 0.001). The association between high physical activity level and T2D was primarily observed in participants without metabolic syndrome (P for interaction < 0.001). Moreover, participants with moderate or high levels of physical activity had significantly decreased fasting blood glucose levels during follow-up when compared to those with low level (P group*time < 0.001)., Conclusion: This study suggested that individuals with prediabetes might benefit from moderate and high levels of physical activity., (© 2024. The Author(s).)

Background: Lung squamous cell carcinoma (LUSCs) is associated with high mortality (20-30%) and lacks of effective treatments. Almost all LUSC exhibit somatic mutations in TP53. Wee1, a tyrosine kinase, regulates the cell cycle at the G2/M checkpoint. In TP53-deficient cells, the dependence on G2/M checkpoints increases. PD0166285 is the first reported drug with inhibitory activity against both Wee1 and PKMYT1., Methods: Protein expression was determined by Western blot analysis. Cell proliferation was assessed using cell colony formation and CCK-8 assays. Cell cycle was performed by PI staining with flow cytometry. Apoptosis was evaluated using Annexin V-Phycoerythrin double staining and flow cytometry. DNA damage was detected through comet assay and immunofluorescence assay. In vivo, apoptosis and anti-tumor effects were assessed using the TUNEL assay, a nude mouse model, and immunohistochemistry (IHC). Co-immunoprecipitation assay was used to detect protein-protein interactions. We analyzed Wee1, PKMYT1, and Stat1 expression in pan-cancer studies using the Ualcan public database and assessed their prognostic implications with Kaplan-Meier curves., Result: PD0166285, a Wee1 inhibitor, effectively inhibits Wee1 activity, promoting cell entry into a mitotic crisis. Moreover, PD0166285 sensitizes cells to cisplatin, enhancing clinical outcomes. Our study demonstrated that PD016628 regulates the cell cycle through Rad51 and results in cell cycle arrest at the G2/M phase. We observed increased apoptosis in tumor cells treated with PD0166285, particularly when combined with cisplatin, indicating an enhanced apoptotic response. The upregulation of γ-H2AX serves as an indicator of mitotic catastrophe. Co-immunoprecipitation and data analysis revealed that apoptosis in LUSC is mediated through the Stat1 pathway, accompanied by decreased levels of Socs3. Furthermore, IHC staining confirmed significant differences in the expression of Phospho-CDK1 and γ-H2AX in LUSCs, suggesting involvement in DNA damage., Conclusions: In summary, our study suggests that PD0166285, an inhibitor of Wee1, sensitizes LUSC cells to cisplatin and modulates DNA damage and apoptosis pathways through Rad51 and Stat1, respectively. These findings highlight the combination of PD0166285 and cisplatin as a promising therapeutic approach for treating LUSC., (© 2024. The Author(s).)

Background: There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities., Methods: Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity., Results: The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P < 0.001) and SMI (48.8 versus 42.2 cm 2 /m 2 , P < 0.001) were significantly higher in males relative to females, with comparable myosteatosis prevalence (15.3 versus 16.7%, P = 0.708). Self-care, usual activities and pain within EQ-5D scale were more prevalent in the sarcopenia compared with non-sarcopenia groups across entire population and stratified by sex. The SMI values exhibited a significantly linear correlation with EQ-5D utility index in male but not female patients (P for non-linearity = 0.281). In multiple analysis, SMI or the presence of sarcopenia was both significantly associated with EQ-5D utility index. Subgroup analyses unveiled no discernible interactions between sarcopenia and EQ-5D utility index., Conclusions: Muscle quantity measured by SMI was associated with declined HRQoL in males rather than females, whereas no associations were found regarding muscle quality measured by IMAC in both sexes. It is tempting to manage sarcopenia by increasing SMI levels as high as possible in hopes of achieving better health consequence. Our findings represent the importance of connecting CT-demarcated body composition abnormalities to meaningful patient-centered outcomes. Future targeted studies with sizable multi-center populations are warranted to clarify this causality, and in consequence develop optimized intervention against sarcopenia/myosteatosis or key determinants concerning impaired HRQoL., (© 2024. The Author(s).)

Background: Neurogenic erectile dysfunction, characterized by neurological repair disorders and progressive corpus cavernosum fibrosis (CCF), is an unbearable disease with limited treatment success. IL-17A exhibits a complex role in tissue remodelling. Nevertheless, the precise role and underlying mechanisms of IL-17A in CCF under denervation remain unclear., Methods: PCR array was employed to identified differentially expressed genes between neurogenic ED and normal rats. IL-17A expression and its main target cells were analyzed using Western blotting, immunofluorescence and immunohistochemistry. The phenotypic regulation of IL-17A on corpus cavernosum smooth muscle cells (CSMCs) was evaluated by cell cycle experiments and SA-β-Gal staining. The mechanism of IL-17A was elucidated using non-target metabolomics and siRNA technique. Finally, IL-17A antagonist and ABT-263 (an inhibitor of B-cell lymphoma 2/w/xL) were utilized to enhance the therapeutic effect in a rat model of neurogenic ED., Results: IL-17A emerged as the most significantly upregulated gene in the corpus cavernosum of model rats. It augmented the senescence transformation and fibrotic response of CSMCs, and exhibited a strong correlation with CCF. Mechanistically, IL-17A facilitated CCF by activating the mTORC2-ACACA signalling pathway, upregulating of CSMCs lipid synthesis and senescence transition, and increasing the secretion of fibro-matrix proteins. In vivo, the blockade of IL-17A-senescence signalling improved erectile function and alleviated CCF in neurogenic ED., Conclusions: IL-17A assumes a pivotal role in denervated CCF by activating the mTORC2-ACACA signalling pathway, presenting itself as a potential therapeutic target for effectively overcoming CCF and erection rehabilitation in neurogenic ED., (© 2024. The Author(s).)

Introduction: Total knee arthroplasty (TKA) is accompanied by severe postoperative pain, which is reported to be an important cause of chronic pain. Ultrasound-guided adductor canal block (ACB) combined with infiltration between the popliteal artery and posterior capsular of the knee (IPACK) has been proven to have a better effect on relieving acute pain after TKA. However, whether it has a significant effect on the incidence of chronic pain after TKA has not been reported. This trial was designed to investigate the effect of ultrasound-guided ACB combined with IPACK on the incidence and intensity of chronic pain after TKA., Methods: In this prospective, randomized, double-blind, placebo-controlled study, 100 subjects scheduled for TKA were randomly (1:1) divided into two groups: the ropivacaine group and the placebo group. Patients in each group received ultrasound-guided ACB + IPACK procedures with 0.25% ropivacaine or equal volume normal saline. All patients received multimodal analgesia. Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary outcome was the incidence of chronic pain at 3 months after TKA by telephone follow-up. In addition, pain intensity in early resting and mobilized states, chronic pain intensity, the time to first rescue analgesia; opioid consumption; CRP and IL-6 after the operation; length of postoperative hospital stay; and cost of hospitalization and postoperative complications; as well as the function of the knee in the early stage after the operation, were recorded., Results: Ninety-one participants were included in the final analysis. At 3 months, the incidence of chronic pain was 30.4% in the ropivacaine group, significantly lower than 51.1% in the placebo group. Compared with the placebo group, the ACB + IPACK with ropivacaine group had significantly lower pain scores at 4 hours, 8 hours, 16 hours, and 24 hours after the operation; increased the knee range of motion at 8 hours and 24 hours after the operation; and a significantly decreased incidence of chronic pain at 3 months after the operation. During the follow-up period, there were no nerve block-related complications in either group., Conclusion: In the context of multimodal analgesia protocols, ACB combined with IPACK before surgery decreases the incidence and intensity of chronic pain 3 months after TKA compared with placebo injection. In addition, it reduces the NRS scores, whether at rest or during mobilization, and improves knee function within 24 hours after TKA., Trial Registration: This trial was registered in the China Clinical Trial Center (registration number ChiCTR2200065300) on November 1, 2022., (© 2024. The Author(s).)

Osteoarthritis (OA) is a chronic joint disease characterized by the degeneration, destruction, and excessive ossification of articular cartilage. The prevalence of OA is rising annually, concomitant with the aging global population and increasing rates of obesity. This condition imposes a substantial and escalating burden on individual health, healthcare systems, and broader social and economic frameworks. The etiology of OA is multifaceted and not fully understood. Current research suggests that the death of chondrocytes, encompassing mechanisms such as cellular apoptosis, pyroptosis, autophagy, ferroptosis and cuproptosis, contributes to both the initiation and progression of the disease. These cell death pathways not only diminish the population of chondrocytes but also exacerbate joint damage through the induction of inflammation and other deleterious processes. This paper delineates the morphological characteristics associated with various modes of cell death and summarizes current research results on the molecular mechanisms of different cell death patterns in OA. The objective is to review the advancements in understanding chondrocyte cell death in OA, thereby offering novel insights for potential clinical interventions., (© 2024. The Author(s).)

Objectives: We explored Trichorhinophalangeal syndrome type 1 (TRPS1) expression in special types of breast carcinoma, and analyzed the correlation between TRPS1 and androgen receptor (AR) expression in triple-negative breast cancer (TNBC)., Methods: TRPS1 expression was analyzed in 801 patients with special types of breast carcinoma. A total of 969 TNBC were used to analyze the correlation between the expression of TRPS1 and AR. TRPS1 expression was evaluated in 1975 cases of breast cancer with different molecular types., Results: A total of 801 special types of breast cancers were stained with TRPS1.TRPS1 was positive in 100% (63/63) of mucinous carcinoma, 100% (7/7) adenoid cystic carcinomas (4 classic adenoid cystic carcinomas and 3 solid-basaloid adenoid cystic carcinomas), 100% (4/4) tubular carcinomas, 100% (2/2) secretory carcinomas, and 99.59% (243/244) invasive lobular carcinomas, 99.26% (267/269) invasive micropapillary carcinomas, 97.44% (38/39) ER-positive neuroendocrine tumors, 94.44% (34/36) metaplastic breast carcinomas (MBCs), 63.73% (65/102) apocrine carcinomas. TRPS1 was negative in all triple-negative neuroendocrine carcinomas (0/7).TRPS1 was positive in 92.86% (26/28) of metastatic special types of breast cancer. TRPS1 and AR expression were analyzed in 969 cases of TNBC. 90.40% were positive for TRPS1, and 42.41% were positive for AR. A significant inverse correlation between TRPS1 and AR expression was shown in TNBC (p < .001). TRPS1 showed a higher positive rate (93.13%) in TNBC compared to GATA binding protein 3 (GATA3), gross cystic disease fluid protein 15 (GCDFP-15) and forkhead box transcription Factor C 1 (FOXC1)., Conclusions: In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC., (© 2024. The Author(s).)

Background: Formal home and community-based care are often considered as the preferable option to institutional care, offering older individuals the convenience of receiving care in their homes. Although research has found that these services may alleviate the burden on informal caregivers, there is a lack of research on which specific types of formal home and community-based care influence informal care provision., Methods: Employing fixed-effects and quantile regression models, this study seeks to explore the effects that various formal home and community-based care services have on reducing the burden of informal care. This study draws data from the Chinese Longitudinal Healthy Longevity Survey 2005, 2008, 2011, 2014, and 2018., Results: Our findings indicate that two types of formal care substantially influence the provision of informal care. The availability of daily living assistance services correlates with reduced informal caregiving hours, especially for those with extensive care needs. The availability of community-based health care services is linked to a reduction in the direct expenses incurred from informal caregiving, especially for those incurring greater direct caregiving costs. These effects are more prominent among urban residents. Other services, such as mental health support and legal advice services, do not demonstrate significant effects on reducing informal care hours and costs., Conclusions: Daily living assistance and community-based health care services play a crucial role in benefiting informal caregivers. It is important to prioritize the expansion of these services, especially among those with greater care needs., (© 2024. The Author(s).)

Background: The effect of fat infiltration in the paraspinal muscles on cervical degenerative disease has been confirmed by multiple studies. However, little is known about fat infiltration in the paraspinal extensors in patients with acute cervical spinal cord injury (SCI). This study aimed to investigate the difference in paraspinal extensor fatty infiltration between patients with acute cervical SCI and healthy controls, and to further explore the protective role of the paravertebral extensor muscles in patients with cervical SCI., Methods: A total of 50 patients with acute cervical SCI admitted to the emergency department from January 2019 to November 2023 were retrospectively analyzed, including 26 males and 24 females, with an average age of 59.60 ± 10.81 years. A control group of 50 healthy middle-aged and elderly individuals was also included, comprising 28 males and 22 females, with an average age of 55.00 ± 8.21 years. Cervical spine magnetic resonance imaging (MRI) was used to measure the cross-sectional areas of the superficial and deep cervical extensor muscles, the corresponding vertebral body cross-sectional areas, and the fat area within the superficial and deep extensor muscle groups using Image J software. Differences between the two groups were compared, and the cervical SCI patients were further analyzed based on the severity of the spinal cord injury and gender differences., Results: The deep fatty infiltration ratio (DFIR) and superficial fatty infiltration ratio (SFIR) at C4-C7 in the cervical SCI group were significantly higher than those in the control group (P < 0.001). The cross-sectional area of the functional deep extensor area (FDEA) relative to the vertebral body area (VBA) and the cross-sectional area of the functional superficial extensor area (FSEA) relative to the VBA at the C5 and C6 levels in the cervical SCI group were significantly lower than those in the control group (P < 0.001, P < 0.001, P = 0.034, P = 0.004 respectively). Among the cervical SCI patients, the cross-sectional areas of the deep extensor area (DEA) and the superficial extensor area (SEA) in males were significantly higher than those in females (P < 0.001). At the C6 and C7 levels, the FDEA/VBA and FSEA/VBA ratios in the male group were higher than those in the female group (P = 0.009, P = 0.022, P = 0.019, P = 0.005, respectively)., Conclusion: Patients with acute cervical SCI exhibit significantly higher fatty infiltration and a greater degree of paravertebral extensor muscle degeneration compared to healthy controls. This finding underscores the importance of the paravertebral extensor muscles in the context of cervical SCI and may guide future therapeutic strategies., (© 2024. The Author(s).)

The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe 2+ (DOX-Fe 2+ ), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe 2+ /sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs., (© 2024. The Author(s).)

Background: Leigh syndrome (LS) is a common mitochondrial disease caused by mutations in both mitochondrial and nuclear genes. Isoleucyl-tRNA synthetase 2 (IARS2) encodes mitochondrial isoleucine-tRNA synthetase, and variants in IARS2 have been reported to cause LS. However, the pathogenic mechanism of IARS2 variants is still unclear., Methods: Two unrelated patients, a 4-year-old boy and a 5-year-old boy diagnosed with LS, were recruited, and detailed clinical data were collected. The DNA of the patients and their parents was isolated from the peripheral blood for the identification of pathogenic variants using next-generation sequencing and Sanger sequencing. The ClustalW program, allele frequency analysis databases (gnomAD and ExAc), and pathogenicity prediction databases (Clinvar, Mutation Taster and PolyPhen2) were used to predict the conservation and pathogenicity of the variants. The gene expression level, oxygen consumption rate (OCR), respiratory chain complex activity, cellular adenosine triphosphate (ATP) production, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (ROS) levels were measured in patient-derived lymphocytes and IARS2-knockdown HEK293T cells to evaluate the pathogenicity of the variants., Results: We reported 2 unrelated Chinese patients manifested with LS who carried biallelic IARS2 variants (c.1&#95;390del and c.2450G > A from a 4-year-old boy, and c.2090G > A and c.2122G > A from a 5-year-old boy), of which c.1&#95;390del and c.2090G > A were novel. Functional studies revealed that the patient-derived lymphocytes carrying c.1&#95;390del and c.2450G > A variants exhibited impaired mitochondrial function due to severe mitochondrial complexes I and III deficiencies, which was also found in IARS2-knockdown HEK293T cells. The compensatory experiments in vitro cell models confirmed the pathogenicity of IARS2 variants since re-expression of wild-type IARS2 rather than mutant IARS2 could rescue complexes I and III deficiency, oxygen consumption, and cellular ATP content in IARS2 knockdown cells., Conclusion: Our results not only expand the gene mutation spectrum of LS, but also reveal for the first time the pathogenic mechanism of IARS2 variants due to a combined deficiency of mitochondrial complexes I and III, which is helpful for the clinical diagnosis of IARS2 mutation-related diseases., (© 2024. The Author(s).)

Background: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown., Methods: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker ® probes, mitochondrial stress, real-time ATP rate and western blotting., Results: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3β signaling pathway to inhibit mitochondria-dependent neuronal apoptosis., Conclusion: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis., (© 2024. The Author(s).)

Background: Evidence on the prevalence of smoking in China remains insufficient, with most previous studies focusing on a single region. However, smoking prevalence exhibits significant inequalities across the entire country. This study aimed to evaluate the risk of tobacco prevalence across the country, taking into account spatial inequalities., Methods: The data used in this study were collected in 23 provinces, 5 autonomous regions, and 4 municipalities directly under the central government in 2022. Large population survey data were used, and a Bayesian geostatistical model was employed to investigate smoking prevalence rates across multiple spatial domains., Findings: Significant spatial variations were observed in smokers and exposure to secondhand smoke across China. Higher levels of smokers and secondhand smoke exposure were observed in western and northeastern regions. Additionally, the autonomous region of Tibet, Shanghai municipality, and Yunnan province had the highest prevalence of smokers, while Tibet, Qinghai province, and Yunnan province had the highest prevalence of exposure to secondhand smoke., Conclusion: We have developed a model-based, high-resolution nationwide assessment of smoking risks and employed rigorous Bayesian geostatistical models to help visualize smoking prevalence predictions. These prediction maps provide estimates of the geographical distribution of smoking, which will serve as strong evidence for the formulation and implementation of smoking cessation policies., Highlights: Our study investigated the prevalence of smokers and exposure to secondhand smoke in different spatial areas of China and explored various factors influencing the smoking prevalence. For the first time, our study applied Bayesian geostatistical modeling to generate a risk prediction map of smoking prevalence, which provides a more intuitive and clear understanding of the spatial disparities in smoking prevalence across different geographical regions, economic levels, and development status. We found significant spatial variations in smokers and secondhand smoke exposure in China, with higher rates in the western and northeastern regions., (© 2024. The Author(s).)

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration., (© 2024. The Author(s).)

Background: This study aimed to investigate whether persistent human papillomavirus integration at the same loci (PHISL) before and after treatment can predict recurrent/residual disease in women with CIN2-3., Methods: A total of 151 CIN2-3 women treated with conization between August 2020 and September 2021 were included. To investigate the precision of HPV integration, we further analyzed HPV integration-positive patients. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and the Youden index for predicting recurrence/residual disease were calculated., Results: Among the 151 enrolled CIN2-3 women, 56 were HPV integration-positive and 95 had HPV integration-negative results. Six (10.7%) experienced recurrence among 56 HPV integration-positive patients, which was more than those in HPV integration-negative patients (one patient, 1.1%). In the 56 HPV integration-positive patients, 12 had positive HPV results after treatment, seven had PHISL, and two had positive cone margin. Among the seven patients who tested with PHISL, six (85.7%) had residual/recurrent disease. PHISL was a prominent predictor of persistent/recurrent disease. The HPV test, the HPV integration test, and PHISL all had a sensitivity of 100% and a NPV of 100% for residual/recurrent disease. PHISL showed better specificity (98.0% vs. 82.0%, p = 0.005) and PPV (85.7% vs. 40.0%, p = 0.001) than the HPV test for predicting recurrence., Conclusions: The HPV-integration-positive CIN2-3 women had much higher relapse rates than HPV-integration-negative CIN2-3 women. The findings indicate that PHISL derived from preoperative and postoperative HPV integration tests may be a precise biomarker for the identification of residual/recurrent CIN 2/3., (© 2024. The Author(s).)

Background: The increasing prevalence of allergies and asthma has led to a growing global socioeconomic burden. Since the outbreak of the COVID-19 pandemic, the health and lifestyles of children and adolescents have changed dramatically. It's unclear how this shift impacted allergy and asthma, with limited studies addressing this question. We aim to explore the difference of the prevalence of allergies and asthma among US children and adolescents during and before the COVID-19 pandemic using a nationally representative sample of US children and adolescents., Methods: This cross-sectional study included 31,503 participants in the National Health Interview Survey (NHIS) between 2018 and 2021. Allergies and asthma were defined on an affirmative response in the questionnaire by a parent or guardian. Chi-square tests were used to compare baseline characteristics with allergies and asthma for categorical variables. Differences in prevalence during and before the COVID-19 pandemic were estimated with weighted logistic regression, adjusting for demographic factors. Interaction analyses explored variations across strata., Results: In US children and adolescents aged 0 to 17, prevalence of any allergy was 26.1% (95% CI, 24.8%- 27.4%) in 2018 and 27.1% (95% CI, 25.9%- 28.2%) in 2021. Thereinto, in 2018, prevalence of respiratory allergies, food allergies and skin allergies were 14.0% (95% CI, 13.1%- 15.0%), 6.5% (95% CI, 5.8%- 7.1%) and 12.6% (95% CI, 11.6%- 13.5%), respectively, and in 2021, 18.8% (95% CI, 17.8%- 19.9%), 5.8% (95% CI, 5.2%- 6.4%) and 10.7% (95% CI, 9.9%- 11.5%), respectively. And prevalence of asthma was 11.1% (95% CI, 10.5%- 11.7%) in 2018-2019 and 9.8% (95% CI, 9.2%- 10.4%) in 2020-2021. Prevalence of respiratory allergies, skin allergies and asthma during and before the COVID-19 pandemic in children and adolescents had statistically significant differences. The differences persisted after adjusting for demographic and socioeconomic variables., Conclusion: Prevalence of respiratory allergies increased and the prevalence of both skin allergies and asthma decreased among US children and adolescents during the COVID-19 pandemic compared with the pre-COVID-19 pandemic. Further research is required to explore the association between allergic diseases and the pandemic, with a particular emphasis on the impact of lifestyle changes resulting from measures to prevent COVID-19 infection., (© 2024. The Author(s).)

Background: Reticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections., Methods: To further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control., Results: In the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens., Conclusion: In this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV., (© 2024. The Author(s).)

Background: Ischemic stroke elicits a complex and sustained immune response in the brain. Immunomodulatory treatments have long held promise for improving stroke outcomes, yet none have succeeded in the clinical setting. This lack of success is largely due to our incomplete understanding of how immune cells respond to stroke. The objective of the current study was to dissect the effect of permanent stroke on microglia, the resident immune cells within the brain parenchyma., Methods: A permanent middle cerebral artery occlusion (pMCAO) model was used to induce ischemic stroke in young male and female mice. Microglia were sorted from fluorescence reporter mice after pMCAO or sham surgery and then subjected to single-cell RNA sequencing analysis. Various methods, including flow cytometry, RNA in situ hybridization, immunohistochemistry, whole-brain imaging, and bone marrow transplantation, were also employed to dissect the microglial response to stroke. Stroke outcomes were evaluated by infarct size and behavioral tests., Results: First, we showed the morphologic and spatial changes in microglia after stroke. We then performed single-cell RNA sequencing analysis on microglia isolated from sham and stroke mice of both sexes. The data indicate no major sexual dimorphism in the microglial response to permanent stroke. Notably, we identified seven potential stroke-associated microglial clusters, including four major clusters characterized by a disease-associated microglia-like signature, a highly proliferative state, a macrophage-like profile, and an interferon (IFN) response signature, respectively. Importantly, we provided evidence that the macrophage-like cluster may represent the long-sought stroke-induced microglia subpopulation with increased CD45 expression. Lastly, given that the IFN-responsive subset constitutes the most prominent microglial population in the stroke brain, we used fludarabine to pharmacologically target STAT1 signaling and found that fludarabine treatment improved long-term stroke outcome., Conclusions: Our findings shed new light on microglia heterogeneity in stroke pathology and underscore the potential of targeting specific microglial populations for effective stroke therapies., (© 2024. The Author(s).)

Background: The association between the triglyceride-glucose (TyG) index and clinical outcomes in patients with both coronary artery disease (CAD) and psoriasis is unclear. This study investigated the association between the TyG index and major adverse cardiovascular events (MACE) in patients with both CAD and psoriasis., Methods: This retrospective cohort study included patients diagnosed with both CAD and psoriasis who underwent coronary angiography at the Fuwai Hospital, Beijing, China, between January 2017 and May 2022. The study endpoint was the occurrence of MACE or end of follow-up time. Multivariate Cox proportional analysis and restricted cubic splines (RCS) were used to determine the association between the TyG index and MACE. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold value of the TyG index for predicting MACE., Results: This study enrolled 293 patients with both CAD and psoriasis, including 258 (88.1%) males with a mean age of 58.89 ± 9.61 years. Patients were divided into four groups based on the TyG quartiles: Q1 (N = 74), Q2 (N = 73), Q3 (N = 73), and Q4 (N = 73). After adjusting for the potential confounders, the TyG index was independently associated with MACE, both as a continuous variable (HR = 1.53, 95% CI = 1.03-2.28, P = 0.035) and as a categorical variable (Q1: reference; Q2: HR = 1.85, 95% CI = 0.88-3.87, P = 0.105; Q3: HR = 2.39, 95% CI = 1.14-5.00, P = 0.021; Q4: HR = 2.19, 95% CI = 1.001-4.81, P = 0.0497; P for trend = 0.039). RCS analysis showed an linear association between the TyG index and MACE (P-overall = 0.027, P-non-linear = 0.589). ROC curve analysis showed that the TyG index of ≥ 8.73 was the optimal threshold value (area under the ROC curve = 0.60, 95% CI 0.53-0.67). TyG index ≥ 8.73 was significantly associated with MACE (HR = 2.10, 95% CI = 1.32-3.34, P = 0.002). After adjustment for confounders, the TyG index showed independent association with MACE (HR = 2.00, 95% CI = 1.17-3.42, P = 0.011)., Conclusions: The TyG index showed a positive linear correlation with MACE in patients with both CAD and psoriasis. The TyG index of ≥ 8.73 might be the optimal threshold for predicting MACE., (© 2024. The Author(s).)

Background: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury., Methods: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression., Results: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones., Conclusion: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes., (© 2024. The Author(s).)

Objective: Self-rated health (SRH) has been documented as an important predictor of quality of life among the elderly and its risk factors are vision-specific among elderly males. The aim of this study was to clarify vision-specific risk factors to SRH among elderly females without dementia in Chinese urban areas., Methods: From March to November 2012, 2147 elderly women in Liaoning Province of China were selected using a stratified sampling method. After cognitive screening, 1956 participants without dementia were finally enrolled. A questionnaire including SRH, visual ability and factors including demographic characteristics, physical conditions, lifestyle factors, social psychological status and social activities were analyzed. Multivariate logistic regression was used to clarify the association of SRH with risk factors, while stepwise multivariate logistic regression was used to examine the vision-specific associations with SRH., Results: The mean age was 73.6 ± 5.82 (mean ± SD). The percentages of good SRH in good and impaired visual ability groups were 36.2% and 24.4%, respectively. Most characteristics between elderly females with different visual abilities were significantly different. Visual ability had interactions with physical conditions, lifestyle factors and social activities to affect SRH. Among elderly females with good visual ability, depressive symptoms, rather than chronic disease had the strongest association with good SRH followed by marital status, regular diet, going out alone to distant places, taking a walk, smoking and alcohol consumption. In the impaired visual ability group, going out alone to distant places had the strongest association with good SRH followed by chronic disease, filial piety, taking a walk, participating in entertainment, ethnicity, quality of sleep, worrying about falling and alcohol consumption., Conclusions: Good SRH status was at a low level especially among elderly females with impaired visual ability and the risk factors differed between elderly females with different visual abilities. Social psychological status was crucial for SRH among elderly females with good visual ability whereas physical conditions were prominent for impaired visual ability group., (© 2024. The Author(s).)

Immune checkpoint blockade therapy targeting the programmed death-1(PD-1) pathway has shown remarkable efficacy and durable response in patients with various cancer types. Early prediction of therapeutic efficacy is important for optimizing treatment plans and avoiding potential side effects. In this work, we developed an efficient machine learning prediction method using routine hematologic and biochemical parameters to predict the efficacy of PD-1 combination treatment in Pan-Cancer patients. A total of 431 patients with nasopharyngeal carcinoma, esophageal cancer and lung cancer who underwent PD-1 checkpoint inhibitor combination therapy were included in this study. Patients were divided into two groups: progressive disease (PD) and disease control (DC) groups. Hematologic and biochemical parameters were collected before and at the third week of PD-1 therapy. Six machine learning models were developed and trained to predict the efficacy of PD-1 combination therapy at 8-12 weeks. Analysis of 57 blood biomarkers before and after three weeks of PD-1 combination therapy through statistical analysis, heatmaps, and principal component analysis did not accurately predict treatment outcome. However, with machine learning models, both the AdaBoost classifier and GBDT demonstrated high levels of prediction efficiency, with clinically acceptable AUC values exceeding 0.7. The AdaBoost classifier exhibited the highest performance among the 6 machine learning models, with a sensitivity of 0.85 and a specificity of 0.79. Our study demonstrated the potential of machine learning to predict the efficacy of PD-1 combination therapy based on changes in hematologic and biochemical parameters., (© 2024. The Author(s).)

Hydrogen sulfide (H 2 S) has emerged as a novel endogenous gas signaling molecule, joining the ranks of nitric oxide (NO) and carbon monoxide (CO). Recent research has highlighted its involvement in various physiological processes, such as promoting root organogenesis, regulating stomatal movement and photosynthesis, and enhancing plant growth, development, and stress resistance. Tobacco, a significant cash crop crucial for farmers' economic income, relies heavily on root development to affect leaf growth, disease resistance, chemical composition, and yield. Despite its importance, there remains a scarcity of studies investigating the role of H 2 S in promoting tobacco growth. This study exposed tobacco seedlings to different concentrations of NaHS (an exogenous H 2 S donor) - 0, 200, 400, 600, and 800 mg/L. Results indicated a positive correlation between NaHS concentration and root length, wet weight, root activity, and antioxidant enzymatic activities (CAT, SOD, and POD) in tobacco roots. Transcriptomic and metabolomic analyses revealed that treatment with 600 mg/L NaHS significantly effected 162 key genes, 44 key enzymes, and two metabolic pathways (brassinosteroid synthesis and aspartate biosynthesis) in tobacco seedlings. The addition of exogenous NaHS not only promoted tobacco root development but also potentially reduced pesticide usage, contributing to a more sustainable ecological environment. Overall, this study sheds light on the primary metabolic pathways involved in tobacco root response to NaHS, offering new genetic insights for future investigations into plant root development., (© 2024. The Author(s).)

Background: Urinary incontinence (UI) is closely related to obesity. The aim of this study is to evaluate the association of a novel anthropometric indicator weight-adjusted-waist index (WWI) with UI., Methods: This cross-sectional study used the data from National Health and Nutrition Examination Survey (NHANES) 2001-2018. Weighted multivariable logistic regression was used to evaluate the relationship between WWI and three types of UI [stress UI (SUI), urgency UI (UUI), and mixed UI (MUI)]. The receiver operating characteristic (ROC) curve and Delong et al.'s test were utilized for comparison of the predictive capability for UI between WWI and body mass index (BMI), waist circumference (WC)., Results: A total of 41,614 participants were included in this study, of whom 23.57% had SUI, 19.24% had UUI, and 9.43% had MUI. In the fully adjusted model, WWI was positively associated with three types of UI [SUI: odds ratio (OR) = 1.19, 95%Confidence interval (CI) 1.13-1.25; UUI: OR = 1.18, 95%CI 1.13-1.24; MUI: OR = 1.19, 95%CI 1.11-1.27, all p < 0.001]. Compared to the lowest WWI interval, the positive correlation between WWI and UI still existed in the highest WWI group after converting WWI to a categorical variable by quartiles (SUI: OR = 1.52, 95%CI 1.35-1.71, p < 0.001; UUI: OR = 1.50, 95%CI 1.33-1.69, p < 0.001; MUI: OR = 1.55, 95%CI 1.32-1.83, p < 0.001). WWI had a stronger prediction for three types of UI than BMI and WC (all p < 0.001)., Conclusion: A higher WWI was linked with an increased likelihood of three types of UI (SUI, UUI, and MUI) in the United State population. Compared to BMI and WC, WWI had a stronger predictive power for UI. WWI may be a better adiposity parameter for evaluating UI., (© 2024. The Author(s).)

Background: International student education has become an important part of higher education and an important symbol to measure the level of higher education. To change the traditional teaching model, here we introduced a combination of Case-Based Learning (CBL)and Flipped Classroom (FC) into the pathophysiology course for international students. This study aimed to explore whether the active learning ability and critical thinking ability of international students can be improved, based on this new teaching model, improving the innovation ability of teachers' team and students' attitude to the reform., Methods: The two chapters of Cardiac Insufficiency and Apoptosis in Pathophysiology are designed as a CBL + FC teaching method. Distribute the Self-assessment Scale on Active Learning and Critical Thinking (SSACT) and satisfaction questionnaire to international students to evaluate teaching reform based on CBL + FC., Results: Compared with the traditional classroom, the online flipped classroom based on CBL has significantly improved the learning enthusiasm, as these students are required to independently complete literature review, actively participate in classroom teaching, learn to use multiple learning strategies, and collaborate with other students to complete PowerPoint (PPT)production. At the same time, the students' ability to raise problems and solve problems has been greatly improved by analyzing clinical cases; By consulting the literature, the theoretical knowledge learned can be better applied to clinical analysis. The results of the satisfaction survey also show that international students are more likely to accept the flipped classroom teaching mode., Conclusions: This teaching mode will stimulate the learning motivation of international students, enhance teaching attraction and increase teaching interaction; At the same time, the CBL + FC teaching method can strengthen the evaluation of international students' in and out of class and online learning, enhance students' active learning ability and critical thinking ability, promote the development of personalized learning, and integrate with international medical education., (© 2024. The Author(s).)

Background: The prevalence of obesity-associated insulin resistance (IR) is increasing along with the increase in obesity rates. In this study, we compared the predictive utility of four alternative indexes of IR [triglyceride glucose index (TyG index), metabolic score for insulin resistance (METS-IR), the triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and homeostatic model assessment of insulin resistance (HOMA-IR)] for all-cause mortality and cardiovascular mortality in the general population based on key variables screened by the Boruta algorithm. The aim was to find the best replacement index of IR., Methods: In this study, 14,653 participants were screened from the National Health and Nutrition Examination Survey (2001-2018). And TyG index, METS-IR, TG/HDL-C and HOMA-IR were calculated separately for each participant according to the given formula. The predictive values of IR replacement indexes for all-cause mortality and cardiovascular mortality in the general population were assessed., Results: Over a median follow-up period of 116 months, a total of 2085 (10.23%) all-cause deaths and 549 (2.61%) cardiovascular disease (CVD) related deaths were recorded. Multivariate Cox regression and restricted cubic splines analysis showed that among the four indexes, only METS-IR was significantly associated with both all-cause and CVD mortality, and both showed non-linear associations with an approximate "U-shape". Specifically, baseline METS-IR lower than the inflection point (41.33) was negatively associated with mortality [hazard ratio (HR) 0.972, 95% CI 0.950-0.997 for all-cause mortality]. In contrast, baseline METS-IR higher than the inflection point (41.33) was positively associated with mortality (HR 1.019, 95% CI 1.011-1.026 for all-cause mortality and HR 1.028, 95% CI 1.014-1.043 for CVD mortality). We further stratified the METS-IR and showed that significant associations between METS-IR levels and all-cause and cardiovascular mortality were predominantly present in the nonelderly population aged < 65 years., Conclusions: In conjunction with the results of the Boruta algorithm, METS-IR demonstrated a more significant association with all-cause and cardiovascular mortality in the U.S. population compared to the other three alternative IR indexes (TyG index, TG/HDL-C and HOMA-IR), particularly evident in individuals under 65 years old., (© 2024. The Author(s).)

Modern intensive cropping systems often contribute to the accumulation of phenolic acids in the soil, which promotes the development of soilborne diseases. This can be suppressed by intercropping. This study analyzed the effects of intercropping on Fusarium wilt based on its effect on photosynthesis under stress by the combination of Fusarium commune and cinnamic acid. The control was not inoculated with F. commune, while the faba bean plants (Vicia faba L.) were inoculated with this pathogen in the other treatments. The infected plants were also treated with cinnamic acid. This study examined the development of Fusarium wilt together with its effects on the leaves, absorption of nutrients, chlorophyll fluorescence parameters, contents of photosynthetic pigments, activities of photosynthetic enzymes, gas exchange parameters, and the photosynthetic assimilates of faba bean from monocropping and intercropping systems. Under monocropping conditions, the leaves of the plants inoculated with F. commune grew significantly less, and there was enhanced occurrence of the Fusarium wilt compared with the control. Compared with the plants solely inoculated with F. commune, the exogenous addition of cinnamic acid to the infected plants significantly further reduced the growth of faba bean leaves and increased the occurrence of Fusarium wilt. A comparison of the combination of F. commune and cinnamic acid in intercropped wheat and faba bean compared with monocropping showed that intercropping improved the absorption of nutrients, increased photosynthetic pigments and its contents, electron transport, photosynthetic enzymes, and photosynthetic assimilates. The combination of these factors reduced the occurrence of Fusarium wilt in faba bean and increased the growth of its leaves. These results showed that intercropping improved the photosynthesis, which promoted the growth of faba bean, thus, reducing the development of Fusarium wilt following the stress of infection by F. commune and cinnamic acid. This research should provide more information to enhance sustainable agriculture., (© 2024. The Author(s).)

Background: Breast cancer is one of the most common malignant tumors in women. Cell division cycle associated 5 (CDCA5), a master regulator of sister chromatid cohesion, was reported to be upregulated in several types of cancer. Here, the function and regulation mechanism of CDCA5 in breast cancer were explored., Methods: CDCA5 expression was identified through immunohistochemistry staining in breast cancer specimens. The correlation between CDCA5 expression with clinicopathological features and prognosis of breast cancer patients was analyzed using a tissue microarray. CDCA5 function in breast cancer was explored in CDCA5-overexpressed/knockdown cells and mice models. Co-IP, ChIP and dual-luciferase reporter assay assays were performed to clarify underlying molecular mechanisms., Results: We found that CDCA5 was expressed at a higher level in breast cancer tissues and cell lines, and overexpression of CDCA5 was significantly associated with poor prognosis of patients with breast cancer. Moreover, CDCA5 knockdown significantly suppressed the proliferation and migration, while promoted apoptosis in vitro. Mechanistically, we revealed that CDCA5 played an important role in promoting the binding of E2F transcription factor 1 (E2F1) to the forkhead box M1 (FOXM1) promoter. Furthermore, the data of in vitro and in vivo revealed that depletion of FOXM1 alleviated the effect of CDCA5 overexpression on breast cancer. Additionally, we revealed that the Wnt/β-catenin signaling pathway was required for CDCA5 induced progression of breast cancer., Conclusions: We suggested that CDCA5 promoted progression of breast cancer via CDCA5/FOXM1/Wnt axis, CDCA5 might serve as a novel therapeutic target for breast cancer treatment., (© 2024. The Author(s).)

Background: Rash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone., Case Presentation: A 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic., Conclusions: In conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing., (© 2024. The Author(s).)

Background: Recent studies on the association between Helicobacter pylori (H. pylori) infection and obesity have reported conflicting results. Therefore, the purpose of our study was to investigate the association of obesity, abdominal obesity, and metabolic obesity phenotypes with H. pylori infection., Methods: A cross-sectional study of 1568 participants aged 20 to 85 was conducted using the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Logistic regression models were employed to evaluate the association of general obesity as defined by body mass index (BMI), abdominal obesity as defined by waist circumference (WC) and waist-height ratio (WHtR), and metabolic obesity phenotypes with H. pylori seropositivity. Subgroup analyses stratified by age were conducted to explore age-specific differences in this association., Results: After grouping individuals according to their WHtR, the prevalence rate of WHtR ≥ 0.5 in H. pylori-seropositive participants was significantly higher than that in H. pylori-seronegative participants (79.75 vs. 68.39, P < 0.001). The prevalence of H. pylori seropositivity in non-abdominal obesity and abdominal obesity defined by WHtR was 24.97% and 31.80%, respectively (P < 0.001). In the subgroup analysis, the adjusted association between abdominal obesity, as defined by the WHtR, and H. pylori seropositivity was significant in subjects aged < 50 years (OR = 2.23; 95% CI, 1.24-4.01; P = 0.01) but not in subjects aged ≥ 50 years (OR = 0.84; 95% CI, 0.35-1.99; P = 0.66). Subjects older than 50 years old had an OR (95% CI) for metabolically healthy obesity of 0.04 (0.01-0.35) compared with the control group. H. pylori seropositivity was consistently not associated with obesity as defined by BMI., Conclusions: Abdominal obesity, as defined by the WHtR, was associated with H. pylori infection in subjects aged ≤ 50 years., (© 2024. The Author(s).)

H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies., (© 2024. The Author(s).)

Background: Cyperus stoloniferus is an important species in coastal ecosystems and possesses economic and ecological value. To elucidate the structural characteristics, variation, and evolution of the organelle genome of C. stoloniferus, we sequenced, assembled, and compared its mitochondrial and chloroplast genomes., Results: We assembled the mitochondrial and chloroplast genomes of C. stoloniferus. The total length of the mitochondrial genome (mtDNA) was 927,413 bp, with a GC content of 40.59%. It consists of two circular DNAs, including 37 protein-coding genes (PCGs), 22 tRNAs, and five rRNAs. The length of the chloroplast genome (cpDNA) was 186,204 bp, containing 93 PCGs, 40 tRNAs, and 8 rRNAs. The mtDNA and cpDNA contained 81 and 129 tandem repeats, respectively, and 346 and 1,170 dispersed repeats, respectively, both of which have 270 simple sequence repeats. The third high-frequency codon (RSCU > 1) in the organellar genome tended to end at A or U, whereas the low-frequency codon (RSCU < 1) tended to end at G or C. The RNA editing sites of the PCGs were relatively few, with only 9 and 23 sites in the mtDNA and cpDNA, respectively. A total of 28 mitochondrial plastid DNAs (MTPTs) in the mtDNA were derived from cpDNA, including three complete trnT-GGU, trnH-GUG, and trnS-GCU. Phylogeny and collinearity indicated that the relationship between C. stoloniferus and C. rotundus are closest. The mitochondrial rns gene exhibited the greatest nucleotide variability, whereas the chloroplast gene with the greatest nucleotide variability was infA. Most PCGs in the organellar genome are negatively selected and highly evolutionarily conserved. Only six mitochondrial genes and two chloroplast genes exhibited Ka/Ks > 1; in particular, atp9, atp6, and rps7 may have undergone potential positive selection., Conclusion: We assembled and validated the mtDNA of C. stoloniferus, which contains a 15,034 bp reverse complementary sequence. The organelle genome sequence of C. stoloniferus provides valuable genomic resources for species identification, evolution, and comparative genomic research in Cyperaceae., (© 2024. The Author(s).)

Right heart failure is a common complication after cardiac surgery, and its mortality remains high. The medical management and veno-arterial extracorporeal membrane oxygenation has shown significant improvement in the majority of cases. However, a minority of patients may still require long-term mechanical circulatory support or heart transplantation. Balloon atrial septostomy is a new method for the prevention and treatment of right heart failure, which may avoid the patient's dependence on mechanical circulatory support. We used this method to try to treat patients with right heart failure after cardiac surgery, and all received good benefits. Therefore, we selected several representative cases to report, in order to guide other qualified cardiac surgeons to carry out relevant clinical practice., (© 2024. The Author(s).)

Background: Chicken coccidiosis is a protozoan disease that leads to considerable economic losses in the poultry industry. Live oocyst vaccination is currently the most effective measure for the prevention of coccidiosis. However, it provides limited protection with several drawbacks, such as poor immunological protection and potential reversion to virulence. Therefore, the development of effective and safe vaccines against chicken coccidiosis is still urgently needed., Methods: In this study, a novel oral vaccine against Eimeria tenella was developed by constructing a recombinant Lactobacillus plantarum (NC8) strain expressing the E. tenella RON2 protein. We administered recombinant L. plantarum orally at 3, 4 and 5 days of age and again at 17, 18 and 19 days of age. Meanwhile, each chick in the commercial vaccine group was immunized with 3 × 10 2 live oocysts of coccidia. A total of 5 × 10 4 sporulated oocysts of E. tenella were inoculated in each chicken at 30 days. Then, the immunoprotection effect was evaluated after E. tenella infection., Results: The results showed that the proportion of CD4 + and CD8 + T cells, the proliferative ability of spleen lymphocytes, inflammatory cytokine levels and specific antibody titers of chicks immunized with recombinant L. plantarum were significantly increased (P < 0.05). The relative body weight gains were increased and the number of oocysts per gram (OPG) was decreased after E. tenella challenge. Moreover, the lesion scores and histopathological cecum sections showed that recombinant L. plantarum can significantly relieve pathological damage in the cecum. The ACI was 170.89 in the recombinant L. plantarum group, which was higher than the 150.14 in the commercial vaccine group., Conclusions: These above results indicate that L. plantarum expressing RON2 improved humoral and cellular immunity and enhanced immunoprotection against E. tenella. The protective efficacy was superior to that of vaccination with the commercial live oocyst vaccine. This study suggests that recombinant L. plantarum expressing the RON2 protein provides a promising strategy for vaccine development against coccidiosis., (© 2024. The Author(s).)

Background: Primary cervical cancer screening and treating precancerous lesions are effective ways to prevent cervical cancer. However, the coverage rates of human papillomavirus (HPV) vaccines and routine screening are low in most developing countries and even some developed countries. This study aimed to explore the benefit of an artificial intelligence-assisted cytology (AI) system in a screening program for a cervical cancer high-risk population in China., Methods: A total of 1231 liquid-based cytology (LBC) slides from women who underwent colposcopy at the Chinese PLA General Hospital from 2018 to 2020 were collected. All women had received a histological diagnosis based on the results of colposcopy and biopsy. The sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV), false-positive rate (FPR), false-negative rate (FNR), overall accuracy (OA), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and Youden index (YI) of the AI, LBC, HPV, LBC + HPV, AI + LBC, AI + HPV and HPV Seq LBC screening strategies at low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) thresholds were calculated to assess their effectiveness. Receiver operating characteristic (ROC) curve analysis was conducted to assess the diagnostic values of the different screening strategies., Results: The Se and Sp of the primary AI-alone strategy at the LSIL and HSIL thresholds were superior to those of the LBC + HPV cotesting strategy. Among the screening strategies, the YIs of the AI strategy at the LSIL + threshold and HSIL + threshold were the highest. At the HSIL + threshold, the AI strategy achieved the best result, with an AUC value of 0.621 (95% CI, 0.587-0.654), whereas HPV testing achieved the worst result, with an AUC value of 0.521 (95% CI, 0.484-0.559). Similarly, at the LSIL + threshold, the LBC-based strategy achieved the best result, with an AUC of 0.637 (95% CI, 0.606-0.668), whereas HPV testing achieved the worst result, with an AUC of 0.524 (95% CI, 0.491-0.557). Moreover, the AUCs of the AI and LBC strategies at this threshold were similar (0.631 and 0.637, respectively)., Conclusions: These results confirmed that AI-only screening was the most authoritative method for diagnosing HSILs and LSILs, improving the accuracy of colposcopy diagnosis, and was more beneficial for patients than traditional LBC + HPV cotesting., (© 2024. The Author(s).)

As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients., (© 2024. The Author(s).)

Background: Early identification of high-risk individuals with cisplatin-induced nephrotoxicity (CIN) is crucial for avoiding CIN and improving prognosis. In this study, we developed and validated a CIN prediction model based on general clinical data, laboratory indications, and genetic features of lung cancer patients before chemotherapy., Methods: We retrospectively included 696 lung cancer patients using platinum chemotherapy regimens from June 2019 to June 2021 as the traing set to construct a predictive model using Absolute shrinkage and selection operator (LASSO) regression, cross validation, and Akaike's information criterion (AIC) to select important variables. We prospectively selected 283 independent lung cancer patients from July 2021 to December 2022 as the test set to evaluate the model's performance., Results: The prediction model showed good discrimination and calibration, with AUCs of 0.9217 and 0.8288, sensitivity of 79.89% and 45.07%, specificity of 94.48% and 94.81%, in the training and test sets respectively. Clinical decision curve analysis suggested that the model has value for clinical use when the risk threshold ranges between 0.1 and 0.9. Precision-Recall (PR) curve shown in recall interval from 0.5 to 0.75: precision gradually declines with increasing Recall, up to 0.9., Conclusions: Predictive models based on laboratory and demographic variables can serve as a beneficial complementary tool for identifying high-risk populations with CIN., (© 2024. The Author(s).)

Background: Exploration of adaptive evolutionary changes at the genetic level in vaginal microbial communities during different stages of cervical cancer remains limited. This study aimed to elucidate the mutational profile of the vaginal microbiota throughout the progression of cervical disease and subsequently establish diagnostic models., Methods: This study utilized a metagenomic dataset consisting of 151 subjects classified into four categories: invasive cervical cancer (CC) (n = 42), cervical intraepithelial neoplasia (CIN) (n = 43), HPV-infected (HPVi) patients without cervical lesions (n = 34), and healthy controls (n = 32). The analysis focused on changes in microbiome abundance and extracted information on genetic variation. Consequently, comprehensive multimodal microbial signatures associated with CC, encompassing taxonomic alterations, mutation signatures, and enriched metabolic functional pathways, were identified. Diagnostic models for predicting CC were established considering gene characteristics based on single nucleotide variants (SNVs)., Results: In this study, we screened and analyzed the abundances of 18 key microbial strains during CC progression. Additionally, 71,6358 non-redundant mutations were identified, predominantly consisting of SNVs that were further annotated into 25,773 genes. Altered abundances of SNVs and mutation types were observed across the four groups. Specifically, there were 9847 SNVs in the HPV-infected group and 14,892 in the CC group. Furthermore, two distinct mutation signatures corresponding to the benign and malignant groups were identified. The enriched metabolic pathways showed limited similarity with only two overlapping pathways among the four groups. HPVi patients exhibited active nucleotide biosynthesis, whereas patients with CC demonstrated a significantly higher abundance of signaling and cellular-associated protein families. In contrast, healthy controls showed a distinct enrichment in sugar metabolism. Moreover, biomarkers based on microbial SNV abundance displayed stronger diagnostic capability (cc.AUC = 0.87) than the species-level biomarkers (cc.AUC = 0.78). Ultimately, the integration of multimodal biomarkers demonstrated optimal performance for accurately identifying different cervical statuses (cc.AUC = 0.86), with an acceptable performance (AUC = 0.79) in the external testing set., Conclusions: The vaginal microbiome exhibits specific SNV evolution in conjunction with the progression of CC, and serves as a specific biomarker for distinguishing between different statuses of cervical disease., (© 2024. The Author(s).)

Background: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions., Methods: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks., Results: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis., Conclusion: Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences., (© 2024. The Author(s).)

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field., (© 2024. The Author(s).)

Background: Intraventricular hemorrhage (IVH) refers to bleeding within the brain's ventricular system, and hydrocephalus is a life-threatening complication of IVH characterized by increased cerebrospinal fluid accumulation in the ventricles resulting in elevated intracranial pressure. IVH poses significant challenges for healthcare providers due to the complexity of the underlying pathophysiology and lack of standardized treatment guidelines. Herein, we performed a systematic review of the treatment strategies for hydrocephalus secondary to IVH., Methods: This systematic review was prospectively registered with PROSPERO (CRD42023450786). The search was conducted in PubMed, Cochrane Library, and Web of Science on July 15, 2023. We included original studies containing valid information on therapy management and outcome of hydrocephalus secondary to primary, spontaneous, and subarachnoid or intracranial hemorrhage following IVH in adults that were published between 2000 and 2023. Glasgow Outcome Scale (GOS) or modified Ranking Scale (mRS) scores during follow-up were extracted as primary outcomes. The risk of bias was assessed using the Newcastle-Ottawa Scale for Cohort Studies or Cochrane Risk of Bias 2.0 Tool., Results: Two hundred and seven patients from nine published papers, including two randomized controlled trials, were included in the analysis. The GOS was used in five studies, while the mRS was used in four. Seven interventions were applied, including craniotomy for removal of hematoma, endoscopic removal of hematoma with/without endoscopic third ventriculostomy (ETV), traditional external ventricular drainage (EVD), and various combinations of EVD, lumbar drainage (LD), and intraventricular fibrinolysis (IVF). Endoscopic removal of hematoma was performed in five of nine studies. Traditional EVD had no obvious benefit compared with new management strategies. Three different combinations of EVD, LD, and IVF demonstrated satisfactory outcomes, although more studies are required to confirm their reliability. Removal of hematoma through craniotomy generated reliable result. Generally, endoscopic removal of hematoma with ETV, removal of hematoma through craniotomy, EVD with IVF, and EVD with early continuous LD were useful., Conclusion: EVD is still crucial for the management of IVH and hydrocephalus. Despite a more reliable result from the removal of hematoma through craniotomy, a trend toward endoscopic approach was observed due to a less invasive profile., (© 2024. The Author(s).)

Background: The presence of infarction in patients with unrecognized myocardial infarction (UMI) is a critical feature in predicting adverse cardiac events. This study aimed to compare the detection rate of UMI using conventional and deep learning reconstruction (DLR)-based late gadolinium enhancement (LGE O and LGE DL , respectively) and evaluate optimal quantification parameters to enhance diagnosis and management of suspected patients with UMI., Methods: This prospective study included 98 patients (68 men; mean age: 55.8 ± 8.1 years) with suspected UMI treated at our hospital from April 2022 to August 2023. LGE O and LGE DL images were obtained using conventional and commercially available inline DLR algorithms. The myocardial signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and percentage of enhanced area (P area ) employing the signal threshold versus reference mean (STRM) approach, which correlates the signal intensity (SI) within areas of interest with the average SI of normal regions, were analyzed. Analysis was performed using the standard deviation (SD) threshold approach (2SD-5SD) and full width at half maximum (FWHM) method. The diagnostic efficacies based on LGE DL and LGE O images were calculated., Results: The SNR DL and CNR DL were two times better than the SNR O and CNR O , respectively (P < 0.05). P area-DL was elevated compared to P area-O using the threshold methods (P < 0.05); however, no intergroup difference was found based on the FWHM method (P > 0.05). The P area-DL and P area-O also differed except between the 2SD and 3SD and the 4SD/5SD and FWHM methods (P < 0.05). The receiver operating characteristic curve analysis revealed that each SD method exhibited good diagnostic efficacy for detecting UMI, with the P area-DL having the best diagnostic efficacy based on the 5SD method (P < 0.05). Overall, the LGE DL images had better image quality. Strong diagnostic efficacy for UMI identification was achieved when the STRM was ≥ 4SD and ≥ 3SD for the LGE DL and LGE O , respectively., Conclusions: STRM selection for LGE DL magnetic resonance images helps improve clinical decision-making in patients with UMI. This study underscored the importance of STRM selection for analyzing LGE DL images to enhance diagnostic accuracy and clinical decision-making for patients with UMI, further providing better cardiovascular care., (© 2024. The Author(s).)

Background: Lymphatic leakage is one of the postoperative complications of neuroblastoma. The purpose of this study is to summarize the clinical characteristics and risk factors of lymphatic leakage and try to find effective prevention and treatment measures., Methods: A retrospective study included 186 children with abdominal neuroblastoma, including 32 children of lymphatic leakage and 154 children of non-lymphatic leakage. The clinical information, surgical data, postoperative abdominal drainage, treatment of lymphatic leakage and prognosis of the two groups were collected and analyzed., Results: The incidence of lymphatic leakage in this cohort was 14% (32 children). Through univariate analysis of lymphatic leakage group and non-lymphatic leakage group, we found that lymphatic leakage increased the complications, prolonged the time of abdominal drainage and hospitalization, and delayed postoperative chemotherapy (p < 0.05). In this cohort, the median follow-up time was 46 (95% CI: 44-48) months. The follow-up data of 7 children were partially missing. 147 children survived, of which 23 had tumor recurrence (5 children recurred in the surgical area). 37 children died, of which 32 had tumor recurrence (9 children recurred in the operation area). In univariate analysis, there was no statistical difference in overall survival (p = 0.21) and event-free survival (p = 0.057) between lymphatic leakage group and non-lymphatic leakage group, while 3-year cumulative incidence of local progression was higher in lymphatic leakage group (p = 0.015). However, through multivariate analysis, we found that lymphatic leakage did not affect event-free survival, overall survival and cumulative incidence of local progression in children with neuroblastoma. Resection of 5 or more lymphatic regions was an independent risk factor for lymphatic leakage after neuroblastoma surgery. All 32 children with lymphatic leakage were cured by conservative treatment without surgery. Of these, 75% (24/32) children were cured by fat-free diet or observation, 25% (8/32) children were cured by total parenteral nutrition. The median drain output at diagnosis in total parenteral nutrition group was higher than that in non-total parenteral nutrition group (p < 0.001). The cut-off value was 17.2 ml/kg/day., Conclusions: Lymphatic leakage does not affect the prognosis of children with neuroblastoma, but long-term drain output caused by lymphatic leakage will still adversely affect postoperative complications and follow-up treatment, which requires attention and active treatment measures. More attention should be paid to the children with 5 or more lymphatic regions resection, and the injured lymphatic vessels should be actively found and ligated after tumor resection to reduce the postoperative lymphatic leakage. Early application of total parenteral nutrition is recommended for those who have drain output at diagnosis of greater than 17.2 ml/kg/day., Level of Evidence: Level III, Treatment study (Retrospective comparative study)., (© 2024. The Author(s).)

Background: Prospective observational studies have demonstrated that the machine learning (ML) -guided noninvasive chromosome screening (NICS) grading system, which we called the noninvasive chromosome screening-artificial intelligence (NICS-AI) grading system, can be used embryo selection. The current prospective interventional clinical study was conducted to investigate whether this NICS-AI grading system can be used as a powerful tool for embryo selection., Methods: Patients who visited our centre between October 2018 and December 2021 were recruited. Grade A and B embryos with a high probability of euploidy were transferred in the NICS group. The patients in the control group selected the embryos according to the traditional morphological grading. Finally, 90 patients in the NICS group and 161 patients in the control group were compared statistically for their clinical outcomes., Results: In the NICS group, the clinical pregnancy rate (70.0% vs. 54.0%, p < 0.001), the ongoing pregnancy rate (58.9% vs. 44.7%, p = 0.001), and the live birth rate (56.7% vs. 42.9%, p = 0.001) were significantly higher than those of the control group. When the female was ≥ 35 years old, the clinical pregnancy rate (67.7% vs. 32.1%, p < 0.001), ongoing pregnancy rate (56.5% vs. 25.0%, p = 0.001), and live birth rate (54.8% vs. 25.0%, p = 0.001) in the NICS group were significantly higher than those of the control group. Regardless of whether the patients had a previous record of early spontaneous abortion or not, the live birth rate of the NICS group was higher than that of the control group (61.0% vs. 46.9%; 57.9% vs. 34.8%; 33.3% vs. 0%) but the differences were not statistically significant., Conclusions: NICS-AI was able to improve embryo utilisation rate, and the live birth rate, especially for those ≥ 35 years old, with transfer of Grade A embryos being preferred, followed by Grade B embryos. NICS-AI can be used as an effective tool for embryo selection in the future., (© 2024. The Author(s).)