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Background: Single-cell transcriptome sequencing (scRNA-seq) has revolutionized the study of immune cells by overcoming the limitations of traditional antibody-based identification and isolation methods. This advancement allows us to obtain comprehensive gene expression profiles from a diverse array of vertebrate species, facilitating the identification of various cell types. Comparative immunology across vertebrates presents a promising approach to understanding the evolution of immune cell types. In this study, we conducted a comparative transcriptome analysis of peripheral blood mononuclear cells (PBMCs) at the single-cell level across 12 species., Results: Our findings shed light on the cellular compositional features of PBMCs, spanning from fish to mammals. Notably, we identified genes that exhibit vertebrate universality in characterizing immune cells. Moreover, our investigation revealed that monocytes have maintained a conserved transcriptional regulatory program throughout evolution, emphasizing their pivotal role in orchestrating immune cells to execute immune programs., Conclusions: This comprehensive analysis provides valuable insights into the evolution of immune cells across vertebrates., Competing Interests: Declarations. Ethics approval and consent to participate: The animal samples used in this study were approved by the Ethics Committee of Qingdao University. The human samples were approved by the Ethics Committee of the Medical College of Qingdao University, and written informed consent was obtained from the donors in accordance with the Declaration of Helsinki. Consent for publication: All authors consented to the publication of this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: The effects of exercise on the health of people with Crohn's disease (CD) remain unclear. This study aimed to explore the perspective of Chinese CD patients on exercise and the quantitative relationship between exercise and patient-reported outcomes., Methods: This study used a mixed methods design consisting of three components. (1) Big data were mined from social media, and latent Dirichlet allocation (LDA) was used to perform cluster analysis on topics related to physical exercise. (2) A seven-step Colaizzi process was used to conduct semistructured interviews to obtain in-depth information about exercise. (3) A cross-sectional study was performed to examine this relationship using the Global Physical Activity Questionnaire (GPAQ) and Patient-reported Outcome Measurement Information System (PROMIS)., Results: LDA yielded a total of 1536 exercise-related posts; eight topics concerning CD patients were obtained through clustering (peer support, exercise therapy, diet, fatigue, exercise type, intestinal symptoms, body constitution and mental health), and 11 patients were interviewed to validate the results of LDA and explore the insight of Chinese CD. We identified two themes: the effects of exercise on people with CD and factors that promote and hinder exercise. A total of 119 patients with CD were surveyed. Considering confounding factors such as disease activity and medication, moderate-intensity recreational PA increased patients' physical function and improved anxiety, depression, fatigue, pain intensity, and pain impact (all p < 0.05). In contrast, high-intensity work may lead to anxiety, depression, fatigue, pain, and pain effects (all p < 0.001). In addition, sedentary behaviour may lead to depression (p = 0.006)., Conclusion: Patients with CD tend to seek guidance on exercise through social media, and they generally believe that exercise is beneficial, especially for their psychological and spiritual health, despite difficulties in exercising. Physical activity may be an important factor affecting patients' psychological health. Crohn's disease has a profound impact on mental and emotional health, reducing patients' quality of life. Exercise is a good habit that can enhance mental, emotional and social health, but there is currently no standard exercise program for patients with Crohn's disease. The exercise experience of Chinese patients with Crohn's disease can be helpful in formulating exercise plans., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of the First School of Clinical Medicine, Zhejiang Chinese Medical University (no. 2024-KL-261-01). Informed consent was obtained from all individual participants (Interviews and cross-sectional studies) for study participation. The text data used for LDA come from the public website Baidu Tieba, a publicly available website. According to the statement of Baidu Tieba (browsing and copying data are for the purpose of obtaining information and cannot be used for commercial purposes), ethical approval was not required for the secondary analysis of publicly available data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The absence of other structural heart disease is a prerequisite for the diagnosis of non-compaction of the ventricular myocardium (NVM). We also observed that the phenomenon of non-compaction in ventricular muscle in some large patent ductus arteriosus (PDA) patients in children. This study was aimed to explore the prognosis of NVM associated with large PDA in children and provide a better understanding of the interplay between genetic and hemodynamic factors that lead to the phenotype of NVM., Methods: We retrospectively analyzed the clinical data of the patients with the diagnosis of NVM with large PDA from January 2015 to January 2022 who underwent the interventional occlusion. We collected the data of the non-compacted myocardium/compacted myocardium (N/C) ratio, the size of the heart, cardiac function measured on color Doppler echocardiography and electrocardiograph (ECG) before and after interventional occlusion., Results: From a total of 504 patients with large PDA underwent occlusion, 20 patients (3.94%; mean age 1.72 ± 1.44 years, 6males and 14 females) were also diagnosed with NVM. The mean diameter of the pulmonary artery end of the PDA was 7.15 ± 1.19 mm. The N/C ratio of all children significantly improved after PDA interventional occlusion with the decreased trend of LVDd and LVDs. The phenomenon of NVM regressed during the follow-up period: 9 cases(45%) after 1 M, 2 cases(10%) after 3 Ms, 4 cases(20%) after 6Ms, 1 case(5%) after 9Ms, 3 cases(15%) after 12Ms, and 1 case(5%) after 24Ms. However, there was no significant difference in the ejection fraction(EF) at all time points (P > 0.05). During the follow-up, the typical complications of NVM, include congestive heart failure, ventricular arrhythmias and thromboembolic events weren't observed in these patients., Conclusion: The phenomenon of NVM in this group maybe secondary to a large PDA. After the primary factors have been removed, hemodynamic changes and a decrease in the left heart's preload favor the complete regression of the NVM., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Medical Research Ethics Committee, Children’s Hospital of Chongqing Medical University (Approval Number: 2023–271). And the study is a retrospective study using medical records obtained from previous clinical diagnosis and treatment, and does not bring unnecessary risks to the subjects, so the Ethics Committee of the Children’s Hospital of Chongqing Medical University has agreed to exempt informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes., Methods: The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011-2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations., Results: In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04-1.16) and the FMI (OR = 1.08, 95% CI = 1.04-1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02-1.16) and the FMI (OR 1.07, 95% CI 1.02-1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear., Conclusions: Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear., Competing Interests: Declarations The protocol for the NHANES study received approval from the Ethics Review Board of the National Center for Health Statistics. Each participant provided written informed consent prior to their involvement in the survey. As this study constitutes a secondary analysis of the publicly available NHANES database, it does not necessitate additional ethical review by the hospital’s ethics committee. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Due to the specific nature of interstitial pregnancy (IP), there are significant risks to both the mother and the foetus in women with a heterotopic interstitial pregnancy (HIP). IP alone has been analysed as a site-specific ectopic pregnancy (EP) in previous studies; however, according to the latest European Society of Human Reproduction and Embryology criteria, IP is classified as a tubal pregnancy. If IP can be classified as a tubal pregnancy, then there is no difference in the effects of these two methods on intrauterine pregnancies (IUPs). Under the premise of timely surgery, disposing of IPs and tubal pregnancy (excluding IPs) should also have no differential effect on IUPs., Methods: Patients with heterotopic fallopian tubal pregnancy (HP-tube) and HIP seen at our hospital from January 2005 to December 2020 were included. All included patients were diagnosed by transvaginal sonography (TVS), and EPs were confirmed by surgery and pathological analysis. The IUP outcomes after surgical treatment of the EPs were compared between the HP-tube group (n = 464) and the HIP group (n = 206). The outcomes of IUPs were evaluated in patients with HIP who underwent either laparoscopy (169 cases) or laparotomy (36 cases)., Results: There was no significant difference in postoperative miscarriage (6.90% vs. 6.80%, odds ratio (OR) = 1.859, 95% confidence interval (CI) (0.807-4.279), p = 0.145); early spontaneous miscarriage (19.61% vs. 18.93%, OR = 0.788, 95% CI (0.495-1.255), p = 0.316); or late miscarriage (0.43% vs. 0.49%, OR = 0.823, 95% CI (0.070-9.661), p = 0.877) between the HP-tube group and the HIP group. There was no significant difference between the two groups in terms of preterm birth (7.33% vs. 6.80%, OR = 1.044, 95% CI (0.509-2.139), p = 0.907), live birth rate (71.60% vs. 73.30%, OR = 1.010, 95% CI (0.670-1.530), p = 0.980), or perinatal mortality rate (2.00% vs. 0.65%, OR = 0.580, 95% CI (0.030-3.590), p = 0.620). Compared to laparotomy for HIPs, laparoscopic treatment was associated with similar rates of postoperative miscarriage (5.33% vs. 13.90%, p = 0.076), live birth rate (72.80% vs. 75.00%, p = 0.948), caesarean Sect. (83.90% vs. 77.80%, p = 0.414)., Conclusions: After early diagnosis and treatment of EPs, patients in the HP-tube and HIP groups achieved comparable outcomes. Laparotomy and laparoscopy for treating HIPs yielded similar pregnancy outcomes., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of CITIC Xiangya Reproductive and Genetic Hospital (Changsha, People’s Republic of China, LL-SC-2023-016). All methods were carried out in accordance with relevant guidelines and regulations, such as the Declaration of Helsinki. The need for informed consent was waived by the Ethics Committee of CITIC Xiangya Reproductive and Genetic Hospital because of the retrospective nature of the study. Consent for Publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Tuberculous spondylitis (TS) and brucellar spondylitis (BS) both cause major long-term morbidity and disability. Though Spondylodiscitis is sensitive to magnetic resonance images, some are difficult to differentiate. This study aims to identify specific bone changes on computed tomography (CT) images, further to differentiate TS from BS., Methods: We retrospectively analyzed and enrolled 70 patients with TS and 65 with BS at our hospital from December 2012 to January 2024. Information of bone destruction and formation, vertebral wall integrity, osteosclerosis, and sequestrum on CT images was collected and compared using the chi-square test or t-test. P < 0.01 was considered statistically significant., Results: Bone destruction was greater in the TS group compared to the BS group (519.55 mm 2 vs. 316.00 mm 2 , t = 6.01, P < 0.001), preferentially involving each third of the vertebral body horizontally (41.22% vs. 16.67%, χ 2  = 77.76, P < 0.001; positive predictive value [PPV] = 80.6%) and the area under the endplate and equatorial portion of the vertebra longitudinally (80.53% vs. 28.20%, χ 2  = 134.19, P < 0.001, PPV = 82.75%). Patients with BS more frequently exhibited fan-shaped osteosclerosis (12.82% vs. 1.15%, χ 2  = 71.30, P < 0.001; PPV = 86.96%), longer bone formation surrounding the vertebra (18.06 mm vs. 1.97 mm, t = 14.28, P < 0.001), and longer anterior bone formation (3.86 mm vs. 0.92 mm, t = 6.51, P < 0.001). Anterior and closed bone formation was more common in the BS group than in the TS group (44.87% vs. 7.63%, χ 2  = 152.53, P < 0.001; PPV = 77.78%). Fragmented and blocked sequestrum was more common in the TS group than in the BS group and tended to spread in and out of the erosions (22.14% vs. 0.64%, PPV = 98.31% and 22.14% vs. 0.00%, PPV = 100%, χ 2  = 102.43, P < 0.001)., Conclusions: TS and BS exhibit specific features of bone formation, bone destruction, and sequestrum on CT imaging. Our findings indicate that bone features on CT can help clinicians distinguish between two spinal infections., Competing Interests: Declarations Ethics approval and consent to participate Ethics approval was from the Medical Ethics Committee of Shandong Provincial Hospital Affiliated to Shandong First Medical University (SZRJJ: NO.2022 − 136). Informed consent was obtained from all study participants. Consent for publication All the authors read and agreed to publish this manuscript. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: In the context of spinal cord injury (SCI), infiltrating macrophages assume prominence as the primary inflammatory cells within the lesion core, where the fibrotic scar is predominantly orchestrated by platelet-derived growth factor receptor beta (PDGFRβ + ) fibroblasts. Galectin-3, a carbohydrate-binding protein of the lectin family, is notably expressed by infiltrating hematogenous macrophages and mediates cell-cell interactions. Although Galectin-3 has been shown to contribute to the endocytic internalization of PDGFRβ in vitro, its specific role in driving fibrotic scar formation after SCI has not been determined., Methods: We employed a crush mid-thoracic (T10) SCI mouse model. Galectin-3 inhibition after SCI was achieved through intrathecal injection of the Galectin-3 inhibitor TD139 or in situ injection of lentivirus carrying Galectin-3-shRNA (Lv-shLgals3). A fibrosis-induced mice model was established by in situ injection of platelet-derived growth factor D (PDGFD) or recombinant Galectin-3 (rGalectin-3) into the uninjured spinal cord. Galectin-3 internalization experiments were conducted in PDGFRβ + fibroblasts cocultured in conditioned medium in vitro., Results: We identified the spatial and temporal correlation between macrophage-derived Galectin-3 and PDGFRβ in fibroblasts from 3 to 56 days post-injury (dpi). Administration of TD139 via intrathecal injection or in situ injection of Lv-shLgals3 effectively mitigated fibrotic scar formation and extracellular matrix deposition within the injured spinal cord, leading to better neurological outcomes and function recovery after SCI. Furthermore, the fibrosis-inducing effects of exogenous PDGFD in the uninjured spinal cord could be blocked by TD139. In vitro experiments further demonstrated the ability of PDGFRβ + fibroblasts to internalize Galectin-3, with Galectin-3 inhibition resulting in reduced PDGFRβ expression., Conclusions: Our finding underscores the pivotal role of macrophage-derived Galectin-3 in modulating the sustained internalized activation of PDGFRβ within fibroblasts, providing a novel mechanistic insight into fibrotic scarring post-SCI., (© 2024. The Author(s).)

The Rho GTPase signaling pathway is responsible for cell-specific processes, including actin cytoskeleton organization, cell motility, cell division, and the transcription of specific genes. The implications of RhoA and the downstream effector ROCK2 in cancer epithelial-mesenchymal transition, migration, invasion, and therapy resistance associated with stem cells highlight the potential of targeting RhoA/ROCK2 signaling in therapy. Tumor relapse can occur due to cancer cells that do not fully respond to adjuvant chemoradiotherapy, targeted therapy, or immunotherapy. Rho signaling-mediated mitotic defects and cytokinesis failure lead to asymmetric cell division, allowing cells to form polyploids to escape cytotoxicity and promote tumor recurrence and metastasis. In this review, we elucidate the significance of RhoA/ROCK2 in the mechanisms of cancer progression and summarize their inhibitors that may improve treatment strategies., (© 2024. The Author(s).)

Background: The COVID-19 pandemic has significantly impacted the psychological well-being of undergraduate nursing students in China. It is vital to have an understanding of their COVID-19 phobia and its predictors, especially during transitions in public health policy., Objective: This study aims to evaluate the situation and factors contributing to COVID-19 phobia among nursing students in Southwestern China., Methods: A cross-sectional study was conducted in December 2022 among nursing undergraduates in southwestern China. A convenience sample of 317 undergraduate nursing students from all grades at a medical university in Chengdu was assessed using the COVID-19 Phobia Scale (C19P)., Results: The mean COVID-19 Phobia Scale (C19P-SC) score was 52.92 (± 13.02), indicating moderate levels of phobia, with gender, chronic disease, and perceived susceptibility being significant predictors. 11.67% of the students reported an infection history, while 81.39% knew an infected individual. Notably, fourth-year students showed significantly higher phobia level than first-year. Gender, chronic disease, perceived susceptibility, and risk significantly predicted COVID-19 phobia, explaining 16.4% of the variance Results of the thematic analysis revealed four main themes related to COVID-19 phobia and career choice among nursing undergraduates: concerns of infection risk, professional commitment, compromise and acceptance, and confronting phobia., Conclusions: This study discovered a significant level of COVID-19 phobia among undergraduate nursing students and identified several risk factors, including being female, having chronic diseases, perceiving a high susceptibility to the virus, and perceiving a high level of harm after infection. These findings highlight the importance of educators focusing on the mental well-being of nursing students, particularly seniors, to reduce the impact of phobia on their social interactions and career aspirations. This will help ensure that they are well-prepared for their future roles in healthcare., (© 2024. The Author(s).)

Background: The stromal cell derived factor 2 (SDF2) relates closely to the occurrence and development of several kind of cancers. There are few studies to investigate the clinicopathological and prognostic significance of SDF2 in gastric cancer (GC) patients., Methods: We detected SDF2 expression in GC and normal gastric tissues using bioinformatics, western blot and immunohistochemistry. Furthermore, we tested the relationship between SDF2 expression and clinicopathological characteristics and prognosis of GC patients., Results: Bioinformatics, western blot and immunohistochemistry results showed that SDF2 expression in GC tissue was higher than that in normal gastric tissue (P < 0.01). SDF2 expression was associated with Borrmann classification III-IV (χ 2  = 6.484, P = 0.011), depth of infiltration T 3 -T 4 (χ 2  = 9.140, P = 0.003), positive lymph node metastasis (χ 2  = 24.945, P = 0.000) and TNM III-IV stage (χ 2  = 9.945, P = 0.002) of GC patients. The Cox regression analysis indicated that distant metastasis M1 stage (HR = 6.026, 95% CI: 1.880-19.318, P = 0.003), TNM III-IV (HR = 1.833, 95% CI: 1.023-3.287, P = 0.042) and SDF2 high expression (HR = 2.091, 95% CI: 1.064-4.108, P = 0.032) were independent risk factors for OS of GC patients. Kaplan-Meier test showed that the OS of GC patients with SDF2 high expression was much poorer than that of GC patients with SDF2 low-expression (χ 2  = 22.925, P = 0.000)., Conclusion: SDF2 expression is high in GC tissue and is correlated with Borrmann classification III-IV, tumor infiltration depth, positive lymph node metastasis and TNM III-IV stage of GC patients. GC patients with SDF2 high-expression have significantly poor OS., (© 2024. The Author(s).)

Background: In the era of tyrosine kinase inhibitor (TKI) treatment, the progression of chronic myeloid leukemia (CML) remains a significant clinical challenge, and genetic biomarkers for the early identification of CML patients at risk for progression are limited. This study explored whether essential circular RNAs (circRNAs) can be used as biomarkers for diagnosing and monitoring CML disease progression and assessing CML prognosis., Methods: Peripheral blood (PB) samples were collected from 173 CML patients (138 patients with chronic phase CML [CML-CP] and 35 patients with accelerated phase/blast phase CML [CML-AP/BP]) and 63 healthy controls (HCs). High-throughput RNA sequencing (RNA-Seq) was used to screen dysregulated candidate circRNAs for a circRNA signature associated with CML disease progression. Quantitative real-time PCR (qRT-PCR) was used for preliminary verification and screening of candidate dysregulated genes, as well as subsequent exploration of clinical applications. Receiver operating characteristic (ROC) curve analysis, Spearman's rho correlation test, and the Kaplan-Meier method were used for statistical analysis., Results: The aberrant expression of hsa&#95;circ&#95;0006010 and hsa&#95;circ&#95;0002903 during CML progression could serve as valuable biomarkers for differentiating CML-AP/BP patients from CMP-CP patients or HCs. In addition, the expression levels of hsa&#95;circ&#95;0006010 and hsa&#95;circ&#95;0002903 were significantly associated with the clinical features of CML patients but were not directly related to the four scoring systems. Furthermore, survival analysis revealed that high hsa&#95;circ&#95;0006010 expression and low hsa&#95;circ&#95;0002903 expression indicated poor progression-free survival (PFS) in CML patients. Finally, PB hsa&#95;circ&#95;0006010 and hsa&#95;circ&#95;0002903 expression at diagnosis may also serve as disease progression surveillance markers for CML patients but were not correlated with PB BCR-ABL1/ABL1 IS ., Conclusions: Our study demonstrated that PB levels of hsa&#95;circ&#95;0006010 and hsa&#95;circ&#95;0002903 may serve as novel diagnostic, surveillance, and prognostic biomarkers for CML disease progression and may contribute to assisting in the diagnosis of CML patients at risk for progression and accurate management of advanced CML patients., (© 2024. The Author(s).)

Background: We aimed to introduce our modified hand-assisted retroperitoneoscopic living donor nephrectomy (HARPLDN) technique and define the learning curve., Methods: One hundred thirty-eight kidney donors who underwent modified HARPLDN by the same surgeon between May 2015 and March 2022 were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome., Results: In total, the mean operative time was 138.2 ± 32.1 min. The median warm ischemic time (WIT) and estimated blood loss were 90 s and 50 ml, respectively. The learning curve for the total operative time was best modeled as a second-order polynomial with the following equation: CUSUM OT (min) = (-0.09 case number 2 ) + (12.88 case number) - 67.77 (R 2  = 0.7875; p<0.05). The CUSUM learning curve included the following three unique phases: phase 1 (the initial 41 cases), representing the initial learning curve; phase 2 (the middle 43 cases), representing expert competence; and phase 3 (the final 54 cases), representing mastery. The overall 6-month graft survival rate was 99.3%, with 94.9% immediate onset of graft function without delayed graft function and 0.7% ureteral complications., Conclusions: Our modified method is safe and effective for living donor nephrectomy and has the advantages of a shorter operating time and optimized WIT. The surgeon can become familiar with the modified HARPLDN after 41 cases and effectively perform the next 97 cases., (© 2024. The Author(s).)

Background: Prior antibiotic exposure has been identified as a risk factor for VAP occurrence, making it a growing concern among clinical practitioners. But there is a lack of systematic research on the types of antibiotics and the duration of exposure that influence VAP occurrence in children at current., Methods: We retrospectively reviewed 278 children admitted to the Pediatric Intensive Care Unit (PICU) and underwent invasive mechanical ventilation (MV) between January 2020 and December 2022. Of these, 171 patients with MV duration ≥ 48 h were included in the study, with 61 of them developing VAP (VAP group) and the remaining 110 as the non-VAP group. We analyzed the relationship between early antibiotic exposure and VAP occurrence., Results: The incidence of VAP was 21.94% (61/278). The VAP group had significantly longer length of hospital stay (32.00 vs. 20.00 days, p<0.001), PICU stay(25.00 vs. 10.00 days, p<0.001), and duration of mechanical ventilation(16.00 vs. 6.00 days, p<0.001) compared to the non-VAP group. The mortality in the VAP group was significantly higher than that in the non-VAP group (36.07% vs. 21.82%, p = 0.044). The VAP group had a significantly higher rate of carbapenem exposure (65.57% vs. 41.82%, p = 0.003) and duration of usage (9.00 vs. 5.00 days, p = 0.004) than the non-VAP group. Vancomycin and/or linezolid exposure rates (57.38% vs. 40.00%, p = 0.029) and duration (8 vs. 4.5 days, p = 0.010) in the VAP group were significantly higher than that in the non-VAP group, either. Multivariate logistic regression analysis identified the use of carbapenem (≥ 7 days) (OR = 5.156, 95% CI: 1.881-14.137, p = 0.001), repeated intubation (OR = 3.575, 95% CI: 1.449-8.823, p = 0.006), and tracheostomy (OR = 5.767, 95% CI:1.686-19.729, p = 0.005) as the independent risk factors for the occurrence of VAP, while early intravenous immunoglobulin (IVIG) was a protective factor against VAP (OR = 0.426, 95% CI: 0.185-0.98, p = 0.045)., Conclusion: Prior carbapenem exposure (more than 7 days) was an independent risk factor for the occurrence of VAP. For critically ill children, reducing carbapenem use and duration as much as possible should be considered., (© 2024. The Author(s).)

Background: The encystation of Acanthamoeba castellanii has important ecological and medical significance. Blocking encystation is the key to preventing transmission and curing infections caused by A. castellanii. The formation of autophagosomes is one of the most important changes that occur during the encystation of Acanthamoeba. Our previous studies have shown that the heat shock protein 20 of A. castellanii (Ac-HSP20) is involved in its encystation. This study aimed to determine the role and mechanism of Ac-HSP20 in regulating autophagy involved in the encystation of A. castellanii., Methods: Immunofluorescence assay, western blotting and transmission electron microscopy were used to analyze the dynamic changes in autophagy during the initiation and continuation of encystation. The knockdown of Ac-HSP20 was performed to clarify its regulation of encystation and autophagy and to elucidate the molecular mechanism by which Ac-HSP20 participates in autophagy to promote cyst maturation., Results: The encystation rates and autophagosomes were significantly decreased by treatment with the autophagy inhibitor 3-MA. The autophagy marker LC3B and autophagic lysosomes increased with the induced duration of encystation and reached the maximum at 48 h. The encystation rate, LC3B expression and autophagosomes decreased when Ac-HSP20 was knocked down by siRNA transfection. In addition, the expression levels of Ac-HSP20 and LC3B increased and the expressions of p-AKT and p-mTOR decreased after 48 h of encystation without knockdown. However, the expressions of p-AKT and p-mTOR increased while the expression of LC3B decreased under the knockdown of Ac-HSP20. Furthermore, the protein expression of LC3B increased when the PI3K/AKT/mTOR signaling pathway was inhibited but decreased when the pathway was activated., Conclusions: The results demonstrated that autophagy is positively correlated with the encystation of A. castellanii, and Ac-HSP20 regulates autophagy to maintain the homeostasis of A. castellanii by inhibiting the PI3K /AKT /mTOR signaling pathway, thus promoting the maturation and stability of encystation., (© 2024. The Author(s).)

Background: Unfavorable temperatures significantly constrain the quality formation of Dendrobium officinale, severely limiting its food demand. Salicylic acid (SA) enhances the resistance of D. officinale to stress and possesses various analogs. The impact and mechanism of the SA family on improving the quality of D. officinale under adverse temperature conditions remains unclear., Results: Combined with molecular docking analysis, chlorophyll fluorescence and metabolic analysis after treatments with SA analogues or extreme temperatures are performed in this study. The results demonstrate that both heat and cold treatments impede several main parameters of chlorophyll fluorescence of D. officinale, including the ΦPSII parameter, a sensitive growth indicator. However, this inhibition is mitigated by SA or its chemically similar compounds. Comprehensive branch imaging of ΦPSII values revealed position-dependent improvement of tolerance. Molecular docking analysis using a crystal structure model of NPR4 protein reveals that the therapeutic effects of SA analogs are determined by their binding energy and the contact of certain residues. Metabolome analysis identifies 17 compounds are considered participating in the temperature-related SA signaling pathway. Moreover, several natural SA analogs such as 2-hydroxycinnamic acid, benzamide, 2-(formylamino) benzoic acid and 3-o-methylgallic acid, are further found to have high binding ability to NPR4 protein and probably enhance the tolerance of D. officinale against unfavorable temperatures through flavone and guanosine monophosphate degradation pathways., Conclusions: These results reveal that the SA family with a high binding capability of NPR4 could improve the tolerance of D. officinale upon extreme temperature challenges. This study also highlights the collaborative role of SA-related natural compounds present in D. officinale in the mechanism of temperature resistance and offers a potential way to develop protective agents for the cultivation of D. officinale., (© 2024. The Author(s).)

Background: Effective interprofessional teamwork is essential for the efficiency, safety and quality of healthcare system services and requires interprofessional education for medical students. Physical education is a simple and easy way to teach teamwork, which translates into team performance in the work environment. This study was conducted to examine the effectiveness of the physical education competition model, instead of the exams model, for improving teamwork skills among medical students., Methods: A quasiexperimental intervention design was used to measure the effect of a 16-week cheerleading programme on subjects' teamwork skills by completing a teamwork scale comprising four subdimensions, namely, personal characteristics, teamwork, leadership, and conflict management, before the start and at the end of the programme, and by comparing nonwinning to winning students to measure the effect of teamwork skills on team performance., Results: A total of 179 students completed the valid baseline and posttest (effective rate = 95.21%). The teamwork scale scores (B M = 4.81, R M = 5.05, p < 0.001) and 4 subdimension scores (personal characteristics p = 0.002, teamwork p = 0.028, leadership p < 0.001, conflict management p < 0.001) were statistically significant. Twenty-two of the 44 items in the scale improved significantly. The differences between students who won the competition and those who did not (N M=4.86, W M=5.14, p<0.01) were statistically significant, with no significant differences in personal characteristics p = 0.183; significant differences in the 3 subdimensions of teamwork p < 0.01, leadership p = 0.024, and conflict management p = 0.037; and a significant increase in 13 out of 44 self-efficacy items on the scale., Conclusions: The "race for exams" physical education programme improved teamwork among medical students, and increased teamwork improved team performance. The "competition instead of examination" physical education programme provides a quantifiable method for improving interprofessional teamwork among medical students., (© 2024. The Author(s).)

Objective: The aim of this study was to assess the association of neutrophil lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), and system inflammation response index (SIRI) with the all-cause mortality and diabetes-cardiovascular mortality in participants with diabetic retinopathy (DR)., Methods: A total of 572 participants with DR from NHANES were included, and divided into survival group (n = 440) and all-cause death group (n = 132). NLR = neutrophil count/lymphocyte count, MLR = monocyte count/lymphocyte count, SIRI = (neutrophil count × monocyte count)/lymphocyte count. We utilized the NHANES Public-Use Linked Mortality File through April 26, 2022, to determine mortality status. Diabetes-cardiovascular death was defined as death resulting from heart disease, cerebrovascular disease, or diabetes mellitus. The Spearson Correlation Analysis, Kaplan-Meier curves, Cox proportional hazards regression models, Restricted cubic spline plots and Decision Curve Analysis were used., Results: The all-cause mortality and diabetes-cardiovascular mortality were significantly higher in NLR ≥ 1.516, MLR ≥ 0.309, SIRI ≥ 0.756, and NLR + MLR + SIRI subgroups than NLR < 1.516, MLR < 0.309, SIRI < 0.756 subgroups, and other participants except NLR + MLR + SIRI (all P < 0.05). The HR of NLR, MLR, SIRI, NLR + MLR + SIRI for all-cause mortality were 1.979(1.13-3.468), 1.850(1.279-2.676), 1.821(1.096-3.025), 1.871(1.296-2.703), respectively. The hazard ratio of NLR, MLR, SIRI, NLR + MLR + SIRI for diabetes-cardiovascular mortality were 2.602(1.028-6.591), 2.673(1.483-4.818), 2.001(0.898-4.459), 2.554(1.426-4.575), respectively. In the restricted cubic spline plots, the relationship between NLR, MLR, SIRI and HR of all-cause mortality and diabetes-cardiovascular mortality was overall as "J" shaped. In both age < 60 and age > 60 years participants, the all-cause mortality and diabetes-cardiovascular mortality were significantly higher in NLR ≥ 1.516, MLR ≥ 0.309, SIRI ≥ 0.756, and NLR + MLR + SIRI subgroups than NLR < 1.516, MLR < 0.309, SIRI < 0.756 subgroups, and other participants except NLR + MLR + SIRI (all P < 0.05)., Conclusion: NLR, MLR, and SIRI may be three independent prognostic predictors for all-cause mortality and diabetes-cardiovascular mortality among individuals with DR. In practical clinical applications, combining NLR, MLR, and SIRI may enhance the prediction of all-cause mortality and diabetes-cardiovascular mortality in DR., (© 2024. The Author(s).)

Background: Acute pancreatitis (AP) is characterized as a systemic inflammatory condition posing challenges in diagnosis and prognosis assessment. Lipid metabolism abnormalities, especially triacylglycerol (TAG) levels, have been reported, indicating their potential as biomarkers in acute pancreatitis. However, the performance of the TAG cycle, including phospholipid and glycerolipid metabolism, in AP patients has not yet been reported., Methods: This study enrolled 91 patients with acute biliary pancreatitis (ABP), 27 with hyperlipidaemic acute pancreatitis (HLAP), and 58 healthy controls (HCs), and their plasma phospholipid and glycerolipid levels were analyzed through liquid chromatography‒mass spectrometry. The phospholipid and glycerolipid contents of plasma collected from AP patients on the first, third, and seventh days of hospitalization were also measured. An orthogonal partial least squares discriminant analysis model served to differentiate the ABP, HLAP and HC groups, and potentially diagnostic lipids were evaluated via receiver operating characteristic curves in both the test and validation sets. Correlations between clinical data and lipids were conducted using Spearman's method. Clustering via the 'mfuzz' R package and the Kruskal‒Wallis H test were conducted to monitor changes during hospitalization., Results: Compared with those in HCs, the levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidic acid (PA) were lower in AP patients, whereas the levels of phosphatidylinositol (PI) and phosphatidylglycerol (PG) showed the opposite trend. Interestingly, TAG levels were positively correlated with white blood cell counts in ABP patients, and TAGs containing 44-55 carbon atoms were highly correlated with plasma TAG levels in HLAP patients. Phospholipid levels exhibited an inverse correlation with AP markers, in contrast to glycerolipids, which demonstrated a positive correlation with these markers. Additionally, PE (O-16:0/20:4) and PE (18:0/22:6) emerged as potential biomarkers because of their ability to distinguish ABP and HLAP patients from HCs, showing area under the curve (AUC) values of 0.932 and 0.962, respectively. PG (16:0/18:2), PG (16:0/20:4), PE (P-16:0/20:2), PE (P-18:2/18:2), PE (P-18:1/20:3), PE (P-18:1/20:4), PE (O-16:0/20:4), and TAG (56:6/FA18:0) were significantly changed in ABP patients who improved. For HLAP patients, PC (18:0/20:3), TAG (48:3/FA18:1), PE (P-18:0/16:0), and TAG (48:4/FA18:2) showed different trends in patients with improvement and deterioration, which might be used for prognosis., Conclusions: Phospholipids and glycerolipids were found to be potential biomarkers in acute pancreatitis, which offers new diagnostic and therapeutic insights into this disease., (© 2024. The Author(s).)

Background: To investigate alterations in choroidal vascularity index among highly myopic adults with fundus tessellation, utilizing optical coherence tomography., Methods: Total of 143 highly myopic adults (234 eyes) with fundus tessellation were collected in this cross-sectional study, which was stratified into different lesion groups based on the novel tessellated fundus classification. Subfoveal choroidal thickness (SFCT), choroidal luminal area (LA), stromal area (SA), total choroidal area (TCA), and choroidal vascularity index (CVI) were analyzed utilizing optical coherence tomography (OCT) with enhanced depth imaging (EDI) mode, enabling precise quantification of these parameters., Results: Comparison analysis demonstrated notable distinctions in spherical equivalent (SE), axial length (AL), and SFCT across the four tessellation grades (p < 0.001). Analysis of the choroidal vascularity parameters, including LA, TCA, and CVI, demonstrated notable disparities across the four groups (p < 0.001), while no significant variations were observed in SA when comparing Grade 1 versus Grade 2, as well as Grade 2 versus Grade 3 (p > 0.05). Logistic regression analyses illustrated that the higher grade of tessellated exhibited a positive association with AL (OR = 1.701, p = 0.027), while negatively associated with SFCT (OR = 0.416, p = 0.007), LA (OR = 0.438, p = 0.010) and CVI (OR = 0.529, p = 0.004). Multiple regression analyses demonstrated a significant negative association between CVI and both SE and AL after adjusting for age, while positively associated with SFCT (p < 0.05)., Conclusion: Subtle choroidal vascularity changes may have a meaningful contribution to the development and progression of fundus tessellation. CVI and LA dramatically decreased during the early stages of tessellation development and maintained a relatively stable status when in the severe tessellated grades., (© 2024. The Author(s).)

Background: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China., Results: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus., Conclusions: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks., (© 2024. The Author(s).)

Background: Fathers can be a critical source of breastfeeding support for their partner, but little is known about what fathers would like to learn about breastfeeding. Partner's support and encouragement enhances mother's breastfeeding confidence and boost the capacity to address breastfeeding difficulties effectively. The aims of this study were to explore what fathers regard as important to learn around breastfeeding, and their current and preferred sources of information., Methods: A structured online survey was conducted, between September 2022 and November 2022, with fathers containing three sections: (1) sociodemographic variables; (2) perceived importance of 26 breastfeeding topics; and (3) sources of breastfeeding information. A convenience sample of expectant and current fathers aged 18 years or older, who were expecting a baby or had a child aged one year or younger, living in Australia, and able to complete survey in English was recruited. Participants were recruited on Facebook advertisement., Results: A total of 174 fathers participated in the study, majority (75%) were aged 30-39 years, current dads (74%), and university educated (69%). The breastfeeding topics that fathers perceived as the most important/ important to learn about were how to work with their partner to overcome breastfeeding challenges, how fathers can be involved with their breastfed baby, the types of support fathers can provide to breastfeeding mothers, what to expect in the first week and the benefits of breastfeeding. The most preferred health professional sources of breastfeeding information were midwives, child and family nurses and doctors. Among non-health professional sources of support, mobile app, friends and family were most popular., Conclusion: Breastfeeding information to enhance fathers' knowledge and awareness of common breastfeeding challenges, and fathers' role in supporting their breastfeeding partner, appear to be (most) important for fathers. Mobile app appears to be among the most preferred non-health professional ways to provide breastfeeding information to fathers., (© 2024. The Author(s).)

Background: The mental health inequality between migrants and non-migrants was exacerbated by the COVID-19 pandemic. Identifying key determinants of this inequality is essential in promoting health equity., Methods: This cross-sectional study recruited Shanghai residents by purposive sampling during the city-wide lockdown (from April 29 to June 1, 2022) using an online questionnaire. Migration statuses (non-migrants, permanent migrants, and temporary migrants) were identified by migration experience and by household registration in Shanghai. Mental health symptoms (depression, anxiety, loneliness, and problematic anger) were assessed by self-report scales. The nonlinear Blinder-Oaxaca decomposition was used to quantify mental health inequality (i.e., differences in predicted probabilities between migration groups) and the contribution of expected correlates (i.e., change in predicted probability associated with variation in the correlate divided by the group difference)., Results: The study included 2738 participants (771 [28.2%] non-migrants; 389 [14.2%] permanent migrants; 1578 [57.6%] temporary migrants). We found inequalities in depression (7.1%) and problematic anger (7.8%) between permanent migrants and non-migrants, and inequalities in anxiety (7.3%) and loneliness (11.3%) between temporary migrants and non-migrants. When comparing permanent migrants and non-migrants, age and social capital explained 12.7% and 17.1% of the inequality in depression, and 13.3% and 21.4% of the inequality in problematic anger. Between temporary migrants and non-migrants, age and social capital also significantly contributed to anxiety inequality (23.0% and 18.2%) and loneliness inequality (26.5% and 16.3%), while monthly household income (20.4%) and loss of monthly household income (34.0%) contributed the most to anxiety inequality., Conclusions: Significant inequalities in depression and problematic anger among permanent migrants and inequalities in anxiety and loneliness among temporary migrants were observed. Strengthening social capital and economic security can aid in public health emergency preparedness and promote mental health equity among migrant populations., (© 2024. The Author(s).)

Background: An increasing number of studies have demonstrated the association of circular RNAs (circRNAs) with the pathological processes of various diseases and their involvement in the onset and progression of multiple cancers. Nevertheless, the functional roles and underlying mechanisms of circRNAs in the autophagy regulation of gastric cancer (GC) have not been fully elucidated., Methods: We used transmission electron microscopy and the mRFP-GFP-LC3 dual fluorescent autophagy indicator to investigate autophagy regulation. The cell counting kit-8 assay, colony formation assay, 5-ethynyl-2'-deoxyuridine incorporation assay, Transwell assay, and Western blot assay were conducted to confirm circPTPN22's influence on GC progression. Dual luciferase reporter assays validated the binding between circPTPN22 and miR-6788-5p, as well as miR-6788-5p and p21-activated kinase-1 (PAK1). Functional rescue experiments assessed whether circPTPN22 modulates PAK1 expression by competitively binding miR-6788-5p, affecting autophagy and other biological processes in GC cells. We investigated the impact of circPTPN22 on in vivo GC tumors using a nude mouse xenograft model. Bioinformatics tools predicted upstream regulatory transcription factors and binding proteins of circPTPN22, while chromatin immunoprecipitation and ribonucleoprotein immunoprecipitation assays confirmed the binding status., Results: Upregulation of circPTPN22 in GC has been shown to inhibit autophagy and promote cell proliferation, migration, and invasion. Mechanistically, circPTPN22 directly binds to miR-6788-5p, subsequently regulating the expression of PAK1, which activates protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) phosphorylation. This modulation ultimately affects autophagy levels in GC cells. Additionally, runt-related transcription factor 1 (RUNX1) negatively regulates circPTPN22 expression, while RNA-binding proteins such as FUS (fused in sarcoma) and ELAVL1 (recombinant ELAV-like protein 1) positively regulate its expression. Inhibition of the autophagy pathway can increase FUS expression, further upregulating circPTPN22 in GC cells, thereby exacerbating the progression of GC., Conclusion: Under the regulation of the transcription factor RUNX1 and RNA-binding proteins FUS and ELAVL1, circPTPN22 activates the phosphorylation of Akt and Erk through the miR-6788-5p/PAK1 axis, thereby modulating autophagy in GC cells. Inhibition of autophagy increases FUS, which in turn upregulates circPTPN22, forming a positive feedback loop that ultimately accelerates the progression of GC., (© 2024. The Author(s).)

Background: Hemiplegic shoulder pain (HSP) is a common complication after stroke. It severely affects the recovery of upper limb motor function. Early shoulder pain in hemiplegic patients is mainly neuropathic caused by central nerve injury or neuroplasticity. Commonly used corticosteroid injections in the shoulder joint can reduce shoulder pain; however, the side effects also include soft tissue degeneration or increased tendon fragility, and the long-term effects remain controversial. Botulinum toxin injections are relatively new and are thought to block the transmission of pain receptors in the shoulder joint cavity and inhibit the production of neuropathogenic substances to reduce neurogenic inflammation. Some studies suggest that the shoulder pain of hemiplegia after stroke is caused by changes in the central system related to shoulder joint pain, and persistent pain may induce the reorganization of the cortical sensory center or motor center. However, there is no conclusive evidence as to whether or not the amelioration of pain by botulinum toxin affects brain function. In previous studies of botulinum toxin versus glucocorticoids (triamcinolone acetonide injection) in the treatment of shoulder pain, there is a lack of observation of differences in changes in brain function. As the content of previous assessments of pain improvement was predominantly subjective, objective quantitative assessment indicators were lacking. Functional near-infrared imaging (fNIRS) can remedy this problem., Methods: This study protocol is designed for a double-blind, randomized controlled clinical trial of patients with post-stroke HSP without biceps longus tenosynovitis or acromion bursitis. Seventy-eight patients will be randomly assigned to either the botulinum toxin type A or glucocorticoid group. At baseline, patients in each group will receive shoulder cavity injections of either botulinum toxin or glucocorticoids and will be followed for 1 and 4 weeks. The primary outcome is change in shoulder pain on the visual analog scale (VAS). The secondary outcome is the assessment of changes in oxyhemoglobin levels in the corresponding brain regions by fNIRS imaging, shoulder flexion, external rotation range of motion, upper extremity Fugl-Meyer, and modified Ashworth score., Discussion: Ultrasound-guided botulinum toxin type A shoulder joint cavity injections may provide evidence of pain improvement in patients with HSP. The results of this trial are also help to analyze the correlation between changes in shoulder pain and changes in cerebral hemodynamics and shoulder joint motor function., Trial Registration: Chinese clinical Trial Registry, ChiCTR2300070132. Registered 03 April 2023, https://www.chictr.org.cn/showproj.html?proj=193722 ., (© 2024. The Author(s).)

Background: Early angiogenesis provides nutrient supply for bone tissue repair, and insufficient angiogenesis will lead tissue engineering failure. Lanthanide metal nanoparticles (LM NPs) are the preferred materials for tissue engineering and can effectively promote angiogenesis. Holmium oxide nanoparticles (HNPs) are LM NPs with the function of bone tissue "tracking" labelling. Preliminary studies have shown that HNPs has potential of promote angiogenesis, but the specific role and mechanism remain unclear. This limits the biological application of HNPs., Results: In this study, we confirmed that HNPs promoted early vessel formation, especially that of H-type vessels in vivo, thereby accelerating bone tissue repair. Moreover, HNPs promoted angiogenesis by increasing cell migration, which was mediated by filopodia extension in vitro. At the molecular level, HNPs interact with the membrane protein EphrinB2 in human umbilical vein endothelial cells (HUVECs), and phosphorylated EphrinB2 can bind and activate VAV2, which is an activator of the filopodia regulatory protein CDC42. When these three molecules were inhibited separately, angiogenesis was reduced., Conclusion: Overall, our study confirmed that HNPs increased cell migration to promote angiogenesis for the first time, which is beneficial for bone repair. The EphrinB2/VAV2/CDC42 signalling pathway regulates cell migration, which is an important target of angiogenesis. Thus, HNPs are a new candidate biomaterial for tissue engineering, providing new insights into their biological application., (© 2024. The Author(s).)

Background: The triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and triglyceride-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute indicators for insulin resistance (IR). This study aimed to compare the predictive value of these indicators for 5-year mortality in critically ill patients with chronic heart failure (CHF)., Methods: Critically ill patients with CHF were identified from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases. The primary outcome was 5-year mortality. The relationship between the three indices and mortality risk was determined using multivariate Cox proportional hazards models, Kaplan-Meier (K‒M) analysis and restricted cubic splines analysis. A receiver operating characteristic (ROC) curve was generated to compare the ability of the three indices to predict mortality. Finally, whether the IR indices would further increase the predictive ability of the basic model including baseline variables with a significance level between survivors and non-survivors was evaluated by ROC curve., Results: Altogether, 1329 patients with CHF were identified from the databases. Cox proportional hazards models indicated that the TyG index was independently associated with an elevated risk of 5-year mortality (hazard ratio [HR], 1.56; 95% confidence interval [CI] 1.29-1.9), while the TyG-BMI index and TG/HDL-C level were significantly associated with 5-year mortality, with an HR (95% CI) of 1.002 (1.000-1.003) and 1.01 (1.00-1.03), respectively. The K-M analysis revealed that the cumulative incidence of all-cause 5-year death increased with increasing quartiles of the TyG index, TyG-BMI index, or TG/HDL-C ratio. According to the ROC curve, the TyG index outperformed the TyG-BMI and TG/HDL-C ratio at predicting all-cause 5-year mortality (0.608 [0.571-0.645] vs. 0.558 [0.522-0.594] vs. 0.561 [0.524-0.598]). The effect of the TyG index on all-cause mortality was consistent across subgroups, with no significant interaction with randomized factors. Furthermore, adding the TyG index to the basic model for 5-year mortality improved its predictive ability (area under the curve, 0.762 for the basic model vs. 0.769 for the basic model + TyG index); however, the difference was not statistically significant., Conclusion: As continuous variables, all three indices were significantly associated with 5-year mortality risk in critically ill patients with CHF. Although these IR indices did not improve the predictive power of the basic model in patients with CHF, the TyG index appears to be the most promising index (vs. TyG-BMI and TG/HDL-C ratio) for prevention and risk stratification in critically ill patients with CHF., (© 2024. The Author(s).)

Background: High temperatures significantly affect the growth, development, and yield of plants. Anoectochilus roxburghii prefers a cool and humid environment, intolerant of high temperatures. It is necessary to enhance the heat tolerance of A. roxburghii and breed heat-tolerant varieties. Therefore, we studied the physiological indexes and transcriptome of A. roxburghii under different times of high-temperature stress treatments., Results: Under high-temperature stress, proline (Pro), H 2 O 2 content increased, then decreased, then increased again, catalase (CAT) activity increased continuously, peroxidase (POD) activity decreased rapidly, then increased, then decreased again, superoxide dismutase (SOD) activity, malondialdehyde (MDA), and soluble sugars (SS) content all decreased, then increased, and chlorophyll and soluble proteins (SP) content increased, then decreased. Transcriptomic investigation indicated that a total of 2740 DEGs were identified and numerous DEGs were notably enriched for "Plant-pathogen interaction" and "Plant hormone signal transduction". We identified a total of 32 genes in these two pathways that may be the key genes for resistance to high-temperature stress in A. roxburghii., Conclusions: To sum up, the results of this study provide a reference for the molecular regulation of A. roxburghii's tolerance to high temperatures, which is useful for further cultivation of high-temperature-tolerant A. roxburghii varieties., (© 2024. The Author(s).)

Background: Breast cancer is one of the common malignancies in women. Evidence has demonstrated that FBXO45 plays a pivotal role in oncogenesis and progression. However, the role of FBXO45 in breast tumorigenesis remains elusive. Exploration of the regulatory mechanisms of FBXO45 in breast cancer development is pivotal for potential therapeutic interventions in patients with breast cancer., Methods: Hence, we used numerous approaches to explore the functions of FBXO45 and its underlaying mechanisms in breast cancer pathogenesis, including CCK-8 assay, EdU assay, colony formation analysis, apoptosis assay, RT-PCR, Western blotting, immunoprecipitation, ubiquitination assay, and cycloheximide chase assay., Results: We found that downregulation of FBXO45 inhibited cell proliferation, while upregulation of FBXO45 elevated cell proliferation in breast cancer. Silencing of FBXO45 induced cell apoptosis, whereas overexpression of FBXO45 inhibited cell apoptosis in breast cancer. Moreover, FBXO45 interacted with BIM and regulated its ubiquitination and degradation. Furthermore, knockdown of FBXO45 inhibited cell proliferation via regulation of BIM pathway. Notably, overexpression of FBXO45 facilitated tumor growth in mice. Strikingly, FBXO45 expression was associated with poor survival of breast cancer patients., Conclusion: Our study could provide the rational for targeting FBXO45 to obtain benefit for breast cancer patients. Altogether, modulating FBXO45/Bim axis could be a promising strategy for breast cancer therapy., (© 2024. The Author(s).)

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally., (© 2024. The Author(s).)

Objective: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally., Methods: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally., Result: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05)., Conclusion: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies., (© 2024. The Author(s).)

Background: Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM)., Objective: This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM., Methods: Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models., Results: This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05)., Conclusions: T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated., (© 2024. The Author(s).)

Background: This study investigated the association between Anti-Müllerian Hormone (AMH) and relevant metabolic parameters and assessed its predictive value in the clinical diagnosis of polycystic ovarian syndrome (PCOS)., Methods: A total of 421 women aged 20-37 years were allocated to the PCOS (n = 168) and control (n = 253) groups, and their metabolic and hormonal parameters were compared. Spearman correlation analysis was conducted to investigate associations, binary logistic regression was used to determine PCOS risk factors, and receiver operating characteristic (ROC) curves were generated to evaluate the predictive value of AMH in diagnosing PCOS., Results: The PCOS group demonstrated significantly higher blood lipid, luteinizing hormone (LH), and AMH levels than the control group. Glucose and lipid metabolism and hormonal disorders in the PCOS group were more significant than in the control group among individuals with and without obesity. LH, TSTO, and AMH were identified as independent risk factors for PCOS. AMH along with LH, and antral follicle count demonstrated a high predictive value for diagnosing PCOS., Conclusion: AMH exhibited robust diagnostic use for identifying PCOS and could be considered a marker for screening PCOS to improve PCOS diagnostic accuracy. Attention should be paid to the effect of glucose and lipid metabolism on the hormonal and related parameters of PCOS populations., (© 2024. The Author(s).)

Background: Supracrestal gingival tissue dimensions (SGTDs) has been considered to be an essential element of periodontal phenotype (PP) components. This study aimed to explore the relationship between SGTDs and other PP components by digital superposition method that integrated cone beam computed tomography (CBCT) with intraoral scanning., Methods: This cross-sectional study was conducted at the Stomatology Hospital of Fujian Medical University. Participants were recruited based on the inclusion and exclusion criteria. The data obtained from the digital scanner (TRIOS 3, 3Shape, Denmark) and CBCT images were imported into the TRIOS software (Implant Studio, 3Shape, Denmark) for computing relevant parameters. The significant level was set at 0.05., Results: A total of 83 participants with 498 maxillary anterior teeth were finally included. The mean values of supracrestal gingival height (SGH) and the distance from the cementoenamel junction (CEJ) to the crest of the alveolar ridge (CEJ-ABC) on the buccal site were significantly higher than palatal SGH (SGH-p) and palatal CEJ-ABC (CEJ-ABC-p). Men exhibited taller CEJ-ABC and SGH-p than women. Additionally, tooth type was significantly associated with the SGH, SGH-p and CEJ-ABC-p. Taller SGH was associated with wider crown, smaller papilla height (PH), flatter gingival margin, thicker bone thickness (BT) and gingival thickness (GT) at CEJ, the alveolar bone crest (ABC), and 2 mm apical to the ABC. Smaller SGH-p displayed thicker BT and GT at CEJ, the ABC, and 2 and 4 mm apical to the ABC. Higher CEJ-ABC showed lower interproximal bone height, smaller PH, flatter gingival margin, thinner GT and BT at CEJ, and 2 mm apical to the ABC. Smaller CEJ-ABC-p displayed thicker BT at CEJ and 2 and 4 mm apical to the ABC. On the buccal, thicker GT was correlated with thicker BT at 2 and 4 mm below the ABC., Conclusion: SGTDs exhibited a correlation with other PP components, especially crown shape, gingival margin and interdental PH. The relationship between SGTDs and gingival and bone phenotypes depended on the apico-coronal level evaluated., Trial Registration: This study was approved by the Biomedical Research Ethics Committee of Stomatology Hospital of Fujian Medical University (approval no. 2023-24)., (© 2024. The Author(s).)

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged., (© 2024. The Author(s).)

Background: Predicting short-term efficacy and intracranial progression-free survival (iPFS) in epidermal growth factor receptor gene mutated (EGFR-mutated) lung adenocarcinoma patients with brain metastases who receive third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy was of great significance for individualized treatment. We aimed to construct and validate nomograms based on clinical characteristics and magnetic resonance imaging (MRI) radiomics for predicting short-term efficacy and intracranial progression free survival (iPFS) of third-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma patients with brain metastases., Methods: One hundred ninety-four EGFR-mutated lung adenocarcinoma patients with brain metastases who received third-generation EGFR-TKI treatment were included in this study from January 1, 2017 to March 1, 2023. Patients were randomly divided into training cohort and validation cohort in a ratio of 5:3. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) regression. Logistic regression analysis and Cox proportional hazards regression analysis were used to screen clinical risk factors. Single clinical (C), single radiomics (R), and combined (C + R) nomograms were constructed in short-term efficacy predicting model and iPFS predicting model, respectively. Prediction effectiveness of nomograms were evaluated by calibration curves, Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to compare the iPFS of high and low iPFS rad-score patients in the predictive iPFS R model and to compare the iPFS of high-risk and low-risk patients in the predictive iPFS C + R model., Results: Overall response rate (ORR) was 71.1%, disease control rate (DCR) was 91.8% and median iPFS was 12.67 months (7.88-20.26, interquartile range [IQR]). There were significant differences in iPFS between patients with high and low iPFS rad-scores, as well as between high-risk and low-risk patients. In short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.867 (0.835-0.900, 95%CI) and 0.803 (0.753-0.854, 95%CI), while in iPFS model, the C-indexes were 0.901 (0.874-0.929, 95%CI) and 0.753 (0.713-0.793, 95%CI)., Conclusions: The third-generation EGFR-TKI showed significant efficacy in EGFR-mutated lung adenocarcinoma patients with brain metastases, and the combined line plot of C + R can be utilized to predict short-term efficacy and iPFS., (© 2024. The Author(s).)

Background: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF., Methods: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF., Results: After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93-0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85-0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88-0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84-0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84-0.95, P = 8 × 10 -4 ), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01-1.15, P = 0.011)., Conclusion: Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies., (© 2024. The Author(s).)

Childhood obesity not only has a negative impact on a child's health but is also a significant risk factor for adult obesity and related metabolic disorders, making it a major global public health concern. Recent studies have revealed the crucial role of gut microbiota in the occurrence and development of obesity, in addition to genetic and lifestyle factors. In this study, we recruited 19 normal-weight children and 47 children with varying degrees of obesity. A questionnaire survey was conducted to inquire about the family background, lifestyle habits and dietary composition of the 66 children. Findings indicate that fathers of obese children tend to be obese themselves, while children with highly educated mothers are more likely to maintain a normal weight. Furthermore, overweight children tend to spend more time on electronic devices and less time on physical activities compared to their normal-weight counterparts. Obese children exhibit significant differences in breakfast and dinner dietary composition when compared to children with normal weight. Additionally, the gut microbiota of these 66 children was analyzed using 16S rRNA sequencing. Analysis of gut microbiota composition showed similar compositions among children with varying degrees of obesity, but significant differences were observed in comparison to normal-weight children. Obese children exhibited a reduced proportion of Bacteroidota and an increased proportion of Firmicutes, resulting in an elevated Firmicutes/Bacteroidota ratio. Moreover, Actinobacteriota were found to be increased in the gut microbiota of children with varying degrees of obesity. PICRUSt analysis indicated significant metabolic differences in the microbiota functions between obese and normal-weight children, suggesting the composition of gut microbiota could be a crucial factor contributing to obesity. These findings provide valuable insights for the treatment of childhood obesity., (© 2024. The Author(s).)

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy., (© 2024. The Author(s).)

Bach2 was initially discovered in B cells, where it was revealed to control the transcription involved in cell differentiation. Bach2 is intimately connected to CD8 + T lymphocytes in various differentiation states and subsets according to recent findings. Bach2 can regulate primitive T cells, stimulate the development and differentiation of memory CD8 + T cells, inhibit the differentiation of effector CD8 + T cells, and play a significant role in the exhaustion of CD8 + T cells. The appearance and development of diseases are tightly linked to irregular CD8 + T cell differentiation and function. Accordingly, Bach2 offers novel approaches and possible targets for the clinical treatment of associated disorders based on research on these pathways. Here, we summarize the role of Bach2 in the function and differentiation of CD8 + T cells and its potential clinical applications., (© 2024. The Author(s).)

Background: This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS., Methods: A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets., Results: This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results., Conclusion: In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis., (© 2024. The Author(s).)

Background: MicroRNAs (miRNAs) are important regulatory factors in the normal developmental stages of the heart and kidney. However, it is currently unclear how miRNA is expressed in type 2 cardiorenal syndrome (CRS). This study aimed to detect the differential expression of miRNAs and to clarify the main enrichment pathways of differentially expressed miRNA target genes in type 2 CRS., Methods: Five cases of healthy control (Group 1), eight of chronic heart failure (CHF, Group 2) and seven of type 2 CRS (Group 3) were enrolled, respectively. Total RNA was extracted from the peripheral blood of each group. To predict the miRNA target genes and biological signalling pathways closely related to type 2 CRS, the Agilent miRNA microarray platform was used for miRNA profiling and bioinformatics analysis of the isolated total RNA samples., Results: After the microarray analysis was done to screen for differentially expressed circulating miRNAs among the three different groups of samples, the target genes and bioinformatic pathways of the differential miRNAs were predicted. A total of 38 differential miRNAs (15 up- and 23 down-regulated) were found in Group 3 compared with Group 1, and a total of 42 differential miRNAs (11 up- and 31 down-regulated) were found in Group 3 compared to Group 2. According to the Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, the top 10 lists of molecular functions, cellular composition and biological processes, and the top 30 signalling pathways of predicted gene targets of the differentially expressed miRNAs were discriminated among the three groups., Conclusion: Between the patients with CHF and type 2 CRS, miRNAs were differentially expressed. Prediction of target genes of differentially expressed miRNAs and the use of GO function and KEGG pathway analysis may reveal the molecular mechanisms of CRS. Circulating miRNAs may contribute to the diagnosis of CRS, and further and larger studies are needed to enhance the robustness of our findings., (© 2024. The Author(s).)

Background: Intramuscular fat (IMF) is an important factor in meat quality, and triglyceride (TG) and Phospholipids (PLIP), as the main components of IMF, are of great significance to the improvement of meat quality., Results: In this study, we used 30 RNA sequences generated from the transcriptome of chicken breast muscle tissues at different developmental stages to construct a gene expression matrix to map RNA sequence reads to the chicken genome and identify the transcript of origin. We used weighted gene co-expression network analysis (WGCNA) and identified 27 co-expression modules, 10 of which were related to TG and PLIP. We identified 150 highly-connected hub genes related to TG and PLIP, respectively, which were found to be mainly enriched in the adipocytokine signaling pathway, MAPK signaling pathway, mTOR signaling pathway, FoxO signaling pathway, and TGF-beta signaling pathway. Additionally, using the BioMart database, we identified 134 and 145 candidate genes related to fat development in the TG-related module and PLIP-related module, respectively. Among them, RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 were identified as candidate genes related to fat development and highly-connected hub genes in the module, suggesting that these ten genes may be important candidate genes affecting IMF deposition., Conclusions: RPS6KB1, BRCA1, CDK1, RPS3, PPARGC1A, ACSL1, NDUFAB1, NDUFA9, ATP5B and PRKAG2 may be important candidate genes affecting IMF deposition. The purpose of this study was to identify the co-expressed gene modules related to chicken IMF deposition using WGCNA and determine key genes related to IMF deposition, so as to lay a foundation for further research on the molecular regulation mechanism underlying chicken fat deposition., (© 2024. The Author(s).)

Background: Ovarian cancer (OC) is a prevalent malignancy in the female reproductive system, and developing effective targeted therapies for this disease remains challenging. The aim of this study was to use clinically-relevant OC models to evaluate the therapeutic effectiveness of RC48, an antibody-drug conjugate (ADC) targeting HER2, either alone or in combination with the VEGFR inhibitor Cediranib Maleate (CM), for the treatment of advanced OC., Methods: OC tumor specimens and cell lines were analyzed to determine HER2 and VEGFR expression by Western blot, immunocytochemistry and immunofluorescence. Moreover, the OC cell lines, cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models were treated with RC48 and/or CM and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for OC both in vitro and in vivo. Additionally, RNA-Seq was performed to investigate the critical mechanism underlying the combination therapy of RC48 and CM., Results: Our results demonstrated that RC48 alone effectively targeted and inhibited the growth of HER2-positive OC tumors in both cell lines and PDX models. Furthermore, the combination of RC48 and CM synergistically induced tumor regression in human OC cell lines, as well as CDX and PDX models. Mechanistically, we observed that the combination treatment inhibited the growth of OC cells involved inducing apoptosis and suppressing cell motility. RNA-seq analysis provided further mechanistic insights and revealed that co-administration of RC48 and CM downregulated multiple cancer-related pathways, including the AKT/mTOR pathway, cell cycle, and cell proliferation. Notably, our data further confirmed that the PI3K-AKT pathway played a key role in the inhibition of proliferation triggered by combinational treatment of RC48 and CM in OC cells., Conclusions: These findings provide a preclinical framework supporting the potential of dual targeting HER2 and VEGFR as a promising therapeutic strategy to improve outcomes in patients with OC., (© 2024. The Author(s).)

Background: The Short Form Qualiveen (SF-Qualiveen) questionnaire assesses the effect of bladder and urinary symptoms on patients' quality of life (QoL) with urological impairment caused by neurological diseases. There is no validated SF-Qualiveen questionnaire in Arabic, so this study aims to provide a translated and validated version of the SF-Qualiveen questionnaire among Arabic-speaking patients with multiple sclerosis (MS)., Methods: The English version of the SF-Qualiveen was translated into Arabic using an algorithm for linguistic and cultural adaptation. MS patients completed the SF-Qualiveen, and the Neurogenic Bladder Symptom Score(NBSS) questionnaire. Psychometric features such as content and construct validity, test-retest reliability, and internal consistency were analyzed. Construct validity was evaluated by contrasting the SF-Qualiveen with the NBSS questionnaire. Internal consistency was measured using Cronbach's alpha, whereas the intraclass correlation coefficient (ICC) was employed to assess the test-retest reliability., Results: One hundred and two patients with MS were included in this study. The internal consistency of the total SF-Qualiveen, and the domains "Bother with limitations," "Fear," "Feeling," and "Frequency of limitations" showed good internal consistency (Cronbach's alpha of > 0.7). ICC was 0.91 for the total score 0.85 for the Bother with limitations, 0.81 for Fears, 0.86 for Feeling, and 0.81 for Frequency of limitations. The correlation analysis revealed a positive association between the total scores on the NBSS and the domains of the SF-Qualiveen, comprising bother with limitations (r = 0.473, p = 0.027), fears (r = 0.611, p = 0.031), feelings (r = 0.572, p = 0.04), and frequency of limitations (r = 0.514, p = 0.013)., Conclusions: The findings of this validation study revealed that the SF-Qualiveen is a reliable and valid instrument appropriate for Arabic-speaking patients with MS in both research and clinical practice., (© 2024. The Author(s).)

Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore's independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field., (© 2024. The Author(s).)

Over the past decade, the role of the 14-3-3 protein has received increasing interest. Seven subtypes of 14-3-3 proteins exhibit high homology; however, each subtype maintains its specificity. The 14-3-3ε protein is involved in various physiological processes, including signal transduction, cell proliferation, apoptosis, autophagy, cell cycle regulation, repolarization of cardiac action, cardiac development, intracellular electrolyte homeostasis, neurodevelopment, and innate immunity. It also plays a significant role in the development and progression of various diseases, such as cardiovascular diseases, inflammatory diseases, neurodegenerative disorders, and cancer. These immense and various involvements of 14-3-3ε in diverse processes makes it a promising target for drug development. Although extensive research has been conducted on 14-3-3 dimers, studies on 14-3-3 monomers are limited. This review aimed to provide an overview of recent reports on the molecular mechanisms involved in the regulation of binding partners by 14-3-3ε, focusing on issues that could help advance the frontiers of this field. Video Abstract., (© 2024. The Author(s).)

Background: This study aimed to validate the availability of superimposing full-color mandibular digital models (DMs) by the morphological characteristics of vessels in extraction adult patients., Methods: Twenty-eight adult patients were included, and their DMs were superimposed with pre- and posttreatment cone beam computed tomography (CBCT) and the morphological characteristics of lingual vessels. The measurements of each tooth were compared under the same coordinate system., Results: The ICC results displayed exceptional agreement in intra- and interrater assessments, with scores exceeding 0.891 in the crown for intrarater agreement and scores surpassing 0.888 in the crown for interrater agreement. Furthermore, no statistically significant differences were found in the 2 superimposition methods (P > 0.05)., Conclusion: The morphological characteristics of vessels under the mucogingival junction in the lingual side of mandible of are stable enough for the superimposition of mandibular DMs in the adult patients undergo orthodontic treatment with premolars extraction., (© 2024. The Author(s).)

Background: The outer membrane vesicles (OMVs) derived from Porphyromonas gingivalis (P. gingivalis) have long been acknowledged for their crucial role in the initiation of periodontitis. However, the implications of P. gingivalis OMVs in the context of cardiovascular disease (CVD) remain incompletely understood. This study aimed to clarify both the impact and the underlying mechanisms through which P. gingivalis OMVs contribute to the propagation of distal cardiovascular inflammation and trauma., Methods: In this study, various concentrations (0, 1.25, 2.5, and 4.5 µg/µL) of P. gingivalis OMVs were microinjected into the common cardinal vein of zebrafish larvae at 48 h post-fertilization (hpf) to assess changes in cardiovascular injury and inflammatory response. Zebrafish larvae from both the PBS and the 2.5 µg/µL injection cohorts were harvested at 30 h post-injection (hpi) for transcriptional analysis. Real-time quantitative PCR (RT-qPCR) was employed to evaluate relative gene expression., Results: These findings demonstrated that P. gingivalis OMVs induced pericardial enlargement in zebrafish larvae, caused vascular damage, increased neutrophil counts, and activated inflammatory pathways. Transcriptomic analysis further revealed the involvement of the immune response and the extracellular matrix (ECM)-receptor interaction signaling pathway in this process., Conclusion: This study illuminated potential mechanisms through which P. gingivalis OMVs contribute to CVD. It accentuated their involvement in distal cardiovascular inflammation and emphasizes the need for further research to comprehensively grasp the connection between periodontitis and CVD., (© 2024. The Author(s).)

Background: The mortality rate of sepsis-associated liver injury (SALI) is relatively high, but there is currently no authoritative prognostic criterion for the outcome of SALI. Meanwhile, lactate-to-albumin ratio (LAR) has been confirmed to be associated with mortality rates in conditions such as sepsis, heart failure, and respiratory failure. However, there is a scarcity of research reporting on the association between LAR and SALI. This study aimed to elucidate the association between LAR and the 28-day mortality rate of SALI., Methods: In this retrospective cohort study, data were obtained from the Medical Information Mart for Intensive Care IV (v2.2). Adult patients with SALI were admitted to the intensive care unit in this study. The LAR level at admission was included, and the primary aim was to assess the relationship between the LAR and 28-day all-cause mortality., Results: A total of 341 patients with SALI (SALI) were screened. They were divided into a survival group (241) and a non-survival group (100), and the 28-day mortality rate was 29.3%. Multivariable Cox regression analysis revealed that for every 1-unit increase in LAR, the 28-day mortality risk for SALI patients increased by 21%, with an HR of 1.21 (95% CI 1.11 ~ 1.31, p < 0.001)., Conclusions: This study indicates that in patients with SALI, a higher LAR is associated with an increased risk of all-cause mortality within 28 days of admission. This suggests that LAR may serve as an independent risk factor for adverse outcomes in SALI patients., (© 2024. The Author(s).)