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An abstract of the conference paper "Postnatally-transmitted HIV-1 variants are efficient at dendritic cell trans-infection and sensitive to autologous and heterologous neutralization," by G. G. Fouda and colleagues is presented.

Background: The lymphatic system is a major route for cancer cell dissemination and also a potential target for antitumor therapy. To investigate whether increased lymphatic vessel density (LVD) is a prognostic factor for nodal metastasis and survival, we studied peritumoral LVD (P-LVD) and intratumoral LVD (I-LVD) in samples from 102 patients with endometrial carcinoma;Methods: Endometrial carcinoma tissues were analyzed for lymphatic vessels by immunohistochemical staining with an antibody against LYVE-1. Univariate analysis was performed with Kaplan-Meier life-table curves to estimate survival, and was compared using the log rank test. Prognostic models used multivariate Cox regression analysis for multivariate analyses of survival;Results: Our study showed that P-LVD, but not I-LVD, was significantly correlated with lymph vascular space invasion (LVSI), lymph node metastasis, tumor stage, and CD44 expression in endometrial carcinoma. Moreover, P-LVD was an independent prognostic factor for progression-free survival and overall survival of endometrial carcinoma;Conclusions: P-LVD may serve as a prognostic factor for endometrial carcinoma. The peritumoral lymphatics might play an important role in lymphatic vessel metastasis. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic stroke is a potentially fatal condition with high mortality and morbidity. However, there is a lack of evidence for this relationship in critically ill patients with hemorrhagic stroke. This study aims to explore the relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients., Methods: The study included 2,026 severe hemorrhagic stroke patients from the Electronic Intensive Care Unit Collaborative Study database, categorized into hypomagnesemia and non-hypomagnesemia groups based on serum magnesium levels. Primary outcome was ICU mortality. Secondary outcome was mechanical ventilation use. Multivariate Cox proportional hazards regression analyses were used to study the relationship between hypomagnesemia and the outcomes. We also performed a cumulative survival rate analysis by Kaplan-Meier curves., Results: A total of 2,026 severe hemorrhagic stroke patients, aged over 16 and hospitalized in the ICU for more than 24 h, were enrolled. Among them, 277 (13.7%) died in the ICU, and hypomagnesemia was observed in 489 patients. Multivariable Cox regression analyses demonstrated that hypomagnesemia was related to a 28% increased risk of ICU mortality (HR 1.28, 95% CI [1.02-1.68], p = 0.035) and a 15% increased risk of mechanical ventilation use (HR 1.15, 95% CI [1.04-1.33], p = 0.010) in severe hemorrhagic stroke patients., Conclusions: Our findings suggested that hypomagnesemia is associated with increased risks of ICU mortality and mechanical ventilation use in severe hemorrhagic stroke patients. Future randomized, prospective studies are needed to elucidate the role of hypomagnesemia and explore potential interventions., Competing Interests: Declarations. Ethics approval and consent to participate: This database was approved by the Massachusetts Institute of Technology (Cambridge, MA). It was a retrospective analysis of data from a publicly accessible data resource. Informed consent were waived for this manuscript. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Wound healing is a highly coordinated process driven by intricate molecular signaling and dynamic interactions between diverse cell types. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) has been implicated in the regulation of inflammation and tissue repair; however, its specific role in skin wound healing remains unclear. This study highlights the pivotal role of NLRP3 in effective skin wound healing, as demonstrated by delayed wound closure and altered cellular and molecular responses in NLRP3-deficient (NLRP3 -/- ) mice. Histological analysis revealed impaired healing processes, accompanied by reduced expression of key inflammatory mediators, including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and prostaglandin E 2 (PGE 2 ). Deficiencies in apoptosis were evident through altered expression of cysteine-aspartic acid protease 3 (Caspase-3), P53, and B-cell lymphoma-2 (Bcl-2). Furthermore, critical growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), and matrix metalloproteinase-9 (MMP-9) were significantly decreased at the excisional skin wound sites. Furthermore, using co-culture systems, we found that NLRP3 mediated the interaction between macrophages and myofibroblasts. Wild-type fibroblast-conditioned media (MFbCM) enhanced nitric oxide (NO), IL-6, and tumor necrosis factor-α (TNF-α) production in M1 macrophages and arginase activity, chitinase 3-like protein 1 (Ym1), and IL-10 expression in M2 macrophages, effects significantly diminished with NLRP3 -/- MFbCM. Similarly, conditioned media from wild-type M1 or M2 macrophages promoted the expression of FGF-2, VEGF, and MMP-2 expression in myofibroblasts, which was attenuated when using NLRP3 -/- macrophage-conditioned media. PGE 2 levels were reduced in both NLRP3 -/- macrophages and myofibroblasts. Supplementing NLRP3 -/- conditioned media with PGE 2 partially restored the impaired functions, suggesting that PGE 2 acts as a downstream mediator of NLRP3-regulated macrophage-myofibroblast interactions. These findings indicate that NLRP3 is a key regulator of skin wound healing, facilitating macrophage-myofibroblast communication., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were performed according to the regulations of the Administration of Affairs Concerning Experimental Animals in China. The experimental protocol was approved by the Animal Welfare and Research Ethics Committee of the Inner Mongolia Agricultural University (approval ID: NND2022021). Consent for publication: All the authors have read and approved the final manuscript. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Aim and Objectives: To construct a set of scientific and feasible nursing management protocols for early fluid resuscitation in acute pancreatitis (AP) patients that can be used to guide clinical practice and enhance the treatment efficacy in these patients., Background: Fluid resuscitation is a key means of early treatment for AP patients and has become a clinical consensus. Nurses are important practitioners of fluid resuscitation, and there is a lack of specific enforceable nursing management programs., Methods: Through literature research, on-site research, semi-structured interviews, and other preliminary preparations of the first draft of the nursing management program for early fluid resuscitation in acute pancreatitis, the Delphi method was used to conduct two rounds of correspondence with medical and nursing experts, and then statistically analyzed., Results: Fifteen and 14 questionnaires were distributed in two rounds, respectively, and 15 and 14 questionnaires were recovered, respectively. The positive coefficient of experts was 100%, the authority coefficient was 0.970 and 0.975, respectively; the coefficient of variation coefficient was 0.05-0.21 and 0.00-0.20, respectively; the expert coordination coefficients of all levels of indices in this study are 0.166-0.335 and 0.189-0.364, respectively. The P values of the first, second, and third level indices are < 0.05 according to the test of Kendall's harmony coefficient. A total of 5 primary indicators, 11 secondary indicators, and 36 tertiary indicators were used to construct the Nursing Management Program for Early Fluid Resuscitation in Acute Pancreatitis., Conclusions: The constructed nursing management plan for early fluid resuscitation in acute pancreatitis patients puts forward clear requirements and standards for nursing care in the early stage of AP treatment. This plan is scientific, represent good clinical practice, are feasible for nurses to follow, and construct a standardized protocol for the management of early fluid resuscitation in patients with acute pancreatitis., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences Institutional Review Board in accordance with the Declaration of Helsinki. All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was obtained from all individual patients included in the study. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Preeclampsia (PE) is a severe pregnancy complication characterized by hypertension and proteinuria. PE poses a substantial threat to the health of both mothers and fetuses, and currently, there is no definitive treatment available. Recent studies have indicated that the transcription factor GATA1 may be implicated in the pathological processes of PE, but the underlying mechanism remains elusive. NTRK2/cGMP-PKG signaling pathway plays a crucial role in regulating the function and polarization of macrophages, which are key immune cells at the maternal-fetal interface. This study aims to investigate the role of GATA1 in the pathogenesis of PE, with a specific focus on how GATA1-regulated TrkB/cGMP-PKG signaling in macrophages and its dysregulation contribute to the development of preeclampsia., Methods: By employing THP-1 cells, co-culture systems of THP-1 cells and HTR-8/Svneo, HPVECs and Sprague-Dawley (SD) rats, in conjunction with gene knockdown and overexpression techniques, we explored the effects of GATA1 on the TrkB/cGMP-PKG signaling pathway. Transcriptomic sequencing, bioinformatics analysis, animal experiments, and clinical sample collection were conducted to validate the role of GATA1 in PE., Results: Knockdown of GATA1 mitigated the symptoms of PE, and this effect was reversed by overexpression of TrkB. In comparison with the control group, the proportion of M2 cells elevated significantly in the sh-GATA1 group (P < 0.001). In addition, the protein expressions levels of TrkB, cGMP, and PKG were significantly decreased in the sh-GATA1 group were significantly decreased compared with those in the control group (P < 0.001, P < 0.001, P < 0.001, P < 0.05, respectively). Moreover, knockdown of GATA1 significantly promoted the migration rate and blood vessel formation of HTR-8/Svneo cells (P < 0.001, P < 0.05, respectively) which inhibited by overexpression of NTRK2 (P < 0.05, P < 0.01, respectively)., Conclusions: The study demonstrated that knockdown of GATA1 modulates M2 polarization of macrophage through the TrkB/cGMP-PKG signaling pathway, influencing the progression of PE. In addition, significant associations between GATA1 and the TrkB/cGMP-PKG signaling pathway were identified in the transcriptomic data from PE patient placentas., Competing Interests: Declarations. Ethics approval and consent to participate: The present study was approved by the Ethics Committee of the School of Basic Medical Sciences, Shandong University (No. ECSBMSSDU2024-2-84). Consent to participate is not applicable. Consent for publication: Not applicable. Clinical trial registration: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Osteoarthritis (OA) is a common degenerative joint disease that significantly impacts the quality of life, especially among older adults. Testosterone, a critical hormone for musculoskeletal health, has been suggested to influence OA pathogenesis. However, the relationship between low testosterone levels and OA risk remains underexplored in large, representative populations. This study aimed to investigate the association between low testosterone levels and OA risk using data from the National Health and Nutrition Examination Survey (NHANES, 2011-2016)., Methods: This cross-sectional analysis included 4,548 participants from NHANES, a nationally representative U.S., Dataset: Testosterone levels were categorized as low or normal, with low testosterone defined as < 300 ng/dL for men and population-based cutoffs for women. The presence of OA was determined through self-reported physician diagnosis. Multivariable logistic regression models were used to examine the association between testosterone levels and OA risk, adjusting for demographic, socioeconomic, lifestyle, and clinical factors. Restricted cubic spline (RCS) analysis was conducted to evaluate non-linear relationships. Subgroup analyses were performed to assess consistency across key demographic and clinical strata., Results: Among the 4,548 participants, 812 (17.9%) were diagnosed with OA. Participants with OA were older, more likely to be female, and exhibited higher rates of obesity and hyperlipidemia. In fully adjusted models, low testosterone levels were significantly associated with increased OA risk (OR, 1.22; 95% CI, 1.02-1.46; P = 0.028). RCS analysis indicated a non-linear relationship, with a steep increase in OA risk at lower testosterone levels, suggesting a threshold effect. Subgroup analyses demonstrated consistent associations across demographic and clinical groups without significant interactions., Conclusion: Low testosterone levels are independently associated with an increased risk of OA in the U.S., Population: These findings underscore the potential role of hormonal health in OA pathogenesis and highlight the need for longitudinal studies to clarify causal pathways. The observed non-linear relationship suggests that maintaining optimal testosterone levels may be important for joint health, and testosterone replacement therapy could be explored as a preventative strategy for individuals with testosterone deficiency., Competing Interests: Declarations. Ethics approval and informed consent statement: All protocols were approved by the NCHS Ethics Review Board and conducted in accordance with the Declaration of Helsinki, with all NHANES participants providing written informed consent. The Institutional Review Board at our institution classified this analysis as exempt, as the dataset employed was entirely de-identified. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2025. The Author(s).)

Background: Long-term endurance training is associated with structural, functional, and biochemical markers of cardiac dysfunction in highly trained athletes. Many studies have focused on structural changes in the right ventricle (RV) and few have examined functional adaptation of the right ventricle. This meta-analysis aims to compare the changes in right ventricular systolic function between endurance athletes and controls before and after exercise using speckle tracking echocardiography (STE)., Methods: A comprehensive search of relevant studies published before March 19, 2024 that examined RV systolic function using speckle tracking technology was conducted. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used as pooled statistics. Meta regression was employed to identify sources of heterogeneity and publication bias was evaluated by Egger's test and funnel plots. Sensitivity analysis was performed by removing sources of significant change from the results of a single publication to evaluate the stability of the results., Results: Twenty studies were included with 1186 participants. A fixed effect meta-analysis revealed RV global longitudinal strain (GLS) WMD = 0.40, 95% CI (-0.08 ~ 0.89), p = 0.102 and free wall longitudinal strain (FWLS) WMD = 0.62, 95% CI (0.28 ~ 0.96), p < 0.001, random effect models of RV basal strain WMD = 2.94, 95% CI (2.00 ~ 3.88), p < 0.001 and RV apical strain WMD = -0.79, 95% CI (-1.95, 0.37), p = 0.245 between endurance athletes and controls. In addition, a random-effects meta-analysis revealed significant impairments in RV function when assessed by comparing RV GLS pre-endurance versus post endurance exercise WMD = 2.51, 95% CI (1.634 ~ 3.40), p < 0. 001., Conclusion: The evidence obtained thus far suggests that reporting only global right ventricular strain data may obscure segment-specific adaptation changes, and the use of global and segmental strain analysis may help to identify potential functional changes in the right ventricle while differentiating between normal endurance athletes and non-active controls., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

The letter to the editor was written in response to the recent article by Wang et al. "The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery", which is published in Journal of Cardiothoracic Surgery. 2024; 19(1):324. This article concludes that intravenous low-dose S-ketamine during thoracic surgery in older patients significantly reduces the incidences of postoperative delirium and cognitive dysfunction, indicating a potential neuroprotective effect of intraoperative low-dose S-ketamine. In view to the retrospective nature of this study and their inconsistent findings with the results of a recent randomized controlled trial performed in patients undergoing non-cardiac thoracic surgery, we believe that several methodological issues and potential confounders in this study deserve further clarification and discussion before accepting their conclusions. Our main concerns include lacking the times and number of delirium monitoring per postoperative day, alone use of the Confusion Assessment Method form for delirium screening, not providing the factors related to the occurrence of postoperative delirium in the ICU stay, and application of a non-standard definition for postoperative cognitive impairment. We believe that clarification of these issues is useful for improving the transparency of their methodology and facilitating the interpretation of their results., Competing Interests: Declarations. Ethics approval and consent to participate: As our paper is just a letter to the editor that comments a article published in journal, ethics approval and consent are unnecessary. Consent for publication: All authors agree to the contents of the submitted manuscript and acknowledge familiarity with the journal’s instructions for manuscript submission. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The chemokine CCL20, a small cytokine that belongs to the C-C chemokine family, interacts with its homologous receptor CCR6, which is expressed on wide range of cell types. According to current research, the CCL20-CCR6 has been established as acritical player in a diverse range of inflammatory, oncogenic, and autoimmune diseases. Within the respiratory system, CCL20-CCR6 demonstrates heightened expression in conditions such as allergic asthma, chronic airway inflammation, non-small cell lung cancer (NSCLC), chronic obstructive pulmonary disease (COPD), and other respiratory diseases, which is conducive to the inflammatory mediators recruitment and tumor microenvironment remodeling. Numerous studies have demonstrated that therapeutic interventions targeting CCL20 and CCR6, including antibodies and antagonists, have the potential to mitigate disease progression. Despite the promising research prospects surrounding the CCL20-CCR6 chemokine axis, the precise mechanisms underlying its action in respiratory diseases remain largely elusive. In this review, we delve into the potential roles of the CCL20-CCR6 axis within the respiratory system by synthesizing and analyzing current research findings. Our objective is to provide a comprehensive understanding of the CCL20-CCR6 axis and its implications for respiratory health and disease. And we aspire to propel research endeavors in this domain and furnish valuable insights for the development of future therapeutic strategies., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The objective of this study is to investigate the potential association between change in body composition before and after cetuximab-based therapy and the prognostic outcomes among individuals diagnosed with advanced colorectal cancer., Methods: A retrospective analysis was undertaken on a cohort of 81 patients diagnosed with RAS wild-type (WT) metastatic colorectal cancer (mCRC) who were treated with cetuximab-based first-line therapy. To assess relevant body composition parameters, quantitative computed tomography (QCT) scans were conducted both before and after cetuximab treatment. These parameters encompassed measurements of visceral fat area (VFA), subcutaneous fat area (SFA), total muscle area (TMA) at the third lumbar vertebra level (L3), and bone mineral density (BMD) at the first and second vertebrae levels (L1/2). The skeletal muscle index (SMI) was subsequently calculated, and changes in parameters (∆VFA, ∆SFA, ∆SMI, ∆BMD) were standardized., Results: The cut-off values for ∆VFA, ∆SFA, ∆SMI, and ∆BMD were 0.28%, -2.76%, -2.97%, and -7.98%, respectively. CEA, ∆VFA, ∆SMI, and ∆BMD were associated with poor outcomes of cetuximab-based first-line chemotherapy (P < 0.05). The risk of disease progression was higher when ∆VFA < 0.28%, ∆SFA < -2.76%, ∆SMI < -2.97%, and ∆BMD < -7.98%. Multivariate analysis indicated that CEA (HR: 0.396, 95% CI: 0.160-0.980, P = 0.045), ∆VFA (HR: 0.307, 95% CI: 0.145-0.651, P = 0.002), and∆SMI (HR: 0.725, 95% CI: 0.322-1.630, P = 0.001) have significant prognostic value for progression-free survival (PFS) in RAS WT mCRC patients treated with cetuximab-based first-line chemotherapy., Conclusions: CEA, ∆VFA, and ∆SMI are independent predictors for PFS in patients with advanced colorectal cancer. High levels of CEA, ∆VFA, and low levels of ∆SMI may indicate poorer outcomes. CEA, ∆VFA, and ∆SMI can be used to predict PFS in mCRC patients receiving cetuximab-based first-line chemotherapy., Trial Registration: This study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital of Anhui Medical University (Batch No:2024-ZNY-02). All subjects signed an informed consent form., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Anhui Provincial Cancer Hospital of Anhui Medical University(Batch No:2024-ZNY-02). All subjects signed an informed consent form. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Indocyanine green (ICG) is a near-infrared fluorescent dye widely used for intraoperative navigation during liver surgeries because of its non-radioactive nature, high safety, and minimal impact on liver function. However, variability in its dosage and concentration and its low imaging success rates have limited its widespread application. To address these issues, we developed a novel ICG-human serum albumin (ICG-HSA) complex to enhance fluorescence visualization during laparoscopic anatomical liver resection., Methods: This prospective, double-blind, single-center, randomized controlled trial will compare the fluorescence navigation effects of the novel ICG-HSA complex with the guideline-recommended ICG administration scheme. The study will involve patients aged 18 to 75 years with malignant liver tumors. The participants will undergo evaluations at specified time points, and data will be collected using an internet-based electronic data capture system. The primary outcome will be the effectiveness of intraoperative fluorescence imaging, assessed by three independent experts. The secondary outcomes will be conversion to open surgery, the total operative time, intraoperative blood loss, and long-term survival rates., Discussion: The aim of using this novel ICG-HSA complex will be to improve the success rate of fluorescence navigation in liver resection by ensuring better stability and a longer liver retention time compared with free ICG. This study seeks to validate the clinical value of ICG-HSA in enhancing surgical precision and outcomes, ultimately promoting its broader clinical application. The results are expected to provide high-level evidence supporting the safety and efficacy of this new fluorescence imaging agent., Trial Registration: ClinicalTrial.gov NCT06219096. Registered on 1 December 2024., Competing Interests: Declarations. Ethics approval and consent to participate: This prospective study was approved by the Medical Ethics Committee on Biomedical Research, West China Hospital of Sichuan University (Ethics number: 2023 review (2121)). All methods were carried out in accordance with relevant guidelines and regulations. Research involving human participants, human material, or human data is conducted in accordance with the Declaration of Helsinki. The authors confirmed that informed consent was obtained from all subjects. Consent for publication: Not applicable. Competing interests: All of the results will be published. There are no financial interests in this trial and none of the parties concerned has right of veto., (© 2024. The Author(s).)

Background: Postoperative pain usually occur in patients who have undergone functional endoscopic sinus surgery (FESS). Remimazolam and dexmedetomidine could enhance the quality of recovery (QoR) after surgery. The aim of this study was to compare the effects of remimazolam and dexmedetomidine with respect to the QoR-40 score of patients who have undergone FESS., Methods: A total of 120 patients (18-65 years) scheduled for FESS were randomly allocated to Group R, Group D or Group C. Group R received 0.075 mg/kg remimazolam loading and 0.1 mg/kg/h infusion. Group D received dexmedetomidine (1.0 µg/kg loading, 0.5 µg/kg/h infusion). Group C received a placebo equal to dexmedetomidine. Anaesthesia was induced with propofol, sufentanil and cisatracurium. Anaesthesia maintenance was performed via target-controlled infusions (TCIs) of propofol and remifentanil. The primary outcome was the QoR-40 score on the day before surgery and postoperative Day 1 (POD1). The secondary outcomes were the time to return to consciousness, length of stay in the PACU, sedation score upon PACU arrival, pain, postoperative nausea and vomiting (PONV) and cumulative consumption of propofol and remifentanil. Adverse effects were recorded., Results: The total QoR-40 scores (median, IQR) on POD1 decreased less (154.5, 152.0 -159.0) in Groups R and D (155.0, 154.8 -159.3) than in Group C (139.0, 136.8 -142.0) (P < 0.001). The time to return of consciousness and the length of stay in the PACU were significantly shorter in Groups R and C than in Group D (P < 0.001). The level of sedation upon PACU arrival (median, IQR) in Groups R (-2.0, -2.0--1.0) and D (-2.0, -3.0--2.0) was greater than that in Group C (1.0, 0.0 -1.0) (P < 0.001). The cumulative consumption rates of propofol and remifentanil in Groups R and D were lower than that in Group C (P < 0.001). Compared with that in Group C, the pain intensity was lower in Groups R and D (P < 0.001).The number of patients occurring PONV was less in Groups R (3/40) and D (4/40) than in Group C (11/40) (P = 0.024). Fifteen patients had bradycardia in Group D, whereas no bradycardia was noted in Groups R or C (P < 0.001)., Conclusion: Administration of remimazolam could provide a similar QoR to that of dexmedetomidine. In addition, remimazolam may be a promising option for improving the QoR of patients who have undergone FESS., Trial Registration: ChiCTR2300076209. (Prospectively registered). The initial registration date was 27/9/2023., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Medical Ethics Committee of Anqing Medical Center of Anhui Medical University. Written informed consent was obtained from all subjects before surgery. This study was prospective registered in the Chinese Clinical Trial Registry (ChiCTR2300076209). Initial registration date was 27/9/2023. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Different species of sea cucumbers in various regions have diverse preferred habitats and feeding habits. However, detailed research on the correlation between food selection and habitat preference of sea cucumbers, as well as their adaptive adjustments to specific habitat types, is still lacking., Methods: A field study was carried out to explore the relationship between food selection and habitat preference, as well as the adaptation process, of the tropical sea cucumber Stichopus chloronotus, which has specific food preferences. This was achieved using an in situ mesocosm method with three single habitat types: sandy, broken coral branches, and reef. Changes is the prokaryotic community structure of gut contents, revealed by high-throughput sequencing analysis of the 16S rRNA gene, were used as the biomarker. Tax4Fun assessed the metabolic pathways of samples, and FAPROTAX evaluated the biogeochemical cycling processes., Results: Alpha diversity, PCoA, and UPGMA tree analyses consistently revealed that bacterial community structures in the gut contents of S. chloronotus in reef bottom cages (GRee) are closely related to those of wild S. chloronotus collected in September (GWS) and October (GWO) than those from the sandy bottom (GSan) and broken coral branches bottom (GBra) cages. The relative abundance of Ruegeria is one of the dominant genera in the control groups (GWS and GWO), while Synechococcus CC9902 is among the predominant genera in the treatment groups (GSan, GBra and GRee). Functional prediction outcomes from Tax4Fun and FAPROTAX also indicate that the metabolic pathways in the gut contents of the treatment groups are distinct from those of the control groups., Conclusions: Compared with S. chloronotus in single habitat types, wild S. chloronotus showed stronger feeding selectivity and ingested actively larger proportion of Ruegeria sp. For this picky species, hard-substrate habitats that can keep it away from strong waves seem to be more important to than those with good sedimentary food. Inappropriate habitats without stable substrate for attachment may cause an unusual change in food preference of S. chloronotus. Tax4Fun and FAPROTAX functional annotation also confirmed that the adaptive adjustment of S. chloronotus can be completed within a month., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Our research did not involve human participants or samples. No specific permits were required for the described field studies. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The indicators for rapid assessment of the severity of acute cholangitis remain highly debated. Therefore, this study aimed to evaluate the efficacy of various inflammatory and immune-nutritional markers in predicting the severity of acute cholangitis. The prognostic roles of the following markers were investigated: Systemic Immune-Inflammatory Index (SII), Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Albumin (Alb), and Prognostic Nutritional Index (PNI). A total of 139 patients with acute cholangitis were included in the study. The inflammatory and immune-nutritional markers with better predictive efficacy were selected to construct a combined predictive score. According to the survival ROC curve analysis, the combined NLR and PNI score, termed PNS, demonstrated the best prognostic performance with an AUC of 0.853. Multivariable survival analysis identified the following independent prognostic factors: PNS (p = 0.010) and Prothrombin Time (PT) (p = 0.003). The results indicate that PNS = 2 is associated with a higher incidence of severe cholangitis., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was obtained from the patients and this study has been approved by the Ethics Committee of Shanxi Academy of Medical Sciences. The studies were conducted in accordance with the local legislation and institutional requirements. Ethics No.YXLL-2023–249. Our study complies with the Declaration of Helsinki. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Although dyslipidemia has been acknowledged as a risk factor for Alzheimer's disease (AD), the effects of lipid-lowering drugs on AD have not been determined. The primary pathophysiological hallmark of AD is the deposition of amyloid-β (Aβ) plaques in the brain. Plasma Aβ levels are influenced by the transport of Aβ from the central nervous system to the peripheral blood. This study investigates the effects of Probucol, a lipid-lowering and antioxidant drug, on plasma Aβ transport., Methods: A total of 120 hyperlipidemic patients with normal cognition were randomly assigned (1:1 ratio) to receive either Probucol (1000 mg daily for 12 weeks) or a placebo. Plasma Aβ, soluble receptor of advanced glycation end products (sRAGE), and fasting lipid profiles were measured at baseline and every 6 weeks., Results: A total of 108 participants completed the study, with 55 in the Probucol group. The cohort consisted of 58 (53.7%) women, with a mean age of 58.4 ± 8.0 (range, 45-80) years. After 12 weeks of treatment, the changes in plasma Aβ 42 and sRAGE levels significantly differed between the Probucol and placebo groups (ΔAβ 42 : β = 6.827, P = 0.030; ΔsRAGE: β = 98.668, P = 0.004). Furthermore, ΔsRAGE was positively correlated with the change in Aβ 42 (β = 0.018, P = 0.048). When adjusted for ΔsRAGE, the effect of Probucol on plasma Aβ 42 levels was attenuated (β = 5.065, P = 0.116). In the Probucol group only, ΔsRAGE was significantly correlated with oxidized low-density lipoproteins (β = 4.27, P = 0.011), total cholesterol (β = 67.50, P = 0.046), and low-density lipoproteins (β = - 91.01, P = 0.011)., Conclusions: Daily oral administration of Probucol (1000 mg) for 12 weeks significantly increased plasma Aβ 42 levels, likely through modulation of sRAGE. This effect may be attributed to the antioxidant and lipid-lowering properties of Probucol. These findings suggest that Probucol could potentially serve as a protective agent against the pathological processes of AD., Trial Registration: This study was registered on the Chinese Clinical Trial Registry platform in June 2019 (Trial registration number: ChiCTR-1900023542)., Competing Interests: Declarations. Ethics approval and consent to participate: The study complied with the principles of Declaration of Helsinki as revised in 1989. The protocol was approved by the Medical Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University. All participants were aware of the research purpose and signed written informed consent forms prior to study initiation. Consent for publication: All the participants provided written informed consent for the publication of the results of this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: UMEC/VI administered via a combination inhaler is associated with a clinically significant improvement in lung function and health-related quality of life in patients with mild-to-moderate COPD. However, their efficacy compared to other bronchodilator mono or dual therapies still remains unclear., Objective: The objective of this research was to evaluate the therapeutic efficacy of UMEC/VI dual and UMEC/VI/FF triple therapies versus alternative bronchodilator regimens in COPD patients., Methods: A systematic search was conducted using four electronic databases (PubMed, EMBASE, Scopus, and Cochrane Library) to select publications published in peer-reviewed journals written in English. The odds ratio (OR) and risk ratio (RR) was calculated, along with their 95% confidence intervals. We assessed heterogeneity using Cochrane Q and I [2] statistics and the appropriate p-value. The analysis used RevMan 5.4., Results: The current meta-analysis includes 31,814 COPD patients from 17 RCTs. The meta-analysis results demonstrate that the combination of LABA and LAMA provides additive bronchodilation and improved lung function in COPD patients. We found that UMEC/VI dual therapy significantly improved FEV1 (OR 1.98 [95% CI 1.70-2.30]), TDI values (OR 1.97 [95% CI 1.72-2.26]), and reduced SGRQ total scores (OR 1.99 [95% CI 1.71-2.32]), with fewer drug-related adverse events (RR 0.58 [95% CI 0.53-0.64]). Similarly, UMEC/VI/FF triple therapy also showed similar benefits, with significant improvements in FEV1 (OR 1.93 [95% CI 1.73-2.15]), TDI values (OR 2.37 [95% CI 2.15-2.61]), and reduced SGRQ total scores (OR 1.83 [95% CI 1.63-2.05]), and fewer drug-related adverse events (RR 0.53 [95% CI 0.49-0.58])., Conclusion: This systematic review and meta-analysis concludes that UMEC and VI combinations are an efficacious treatment option for symptomatic COPD patients., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable as the study is totally based on the published literature. Clinical trial number: Not applicable. Patient consent for publication: N/A. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The stress hyperglycemia ratio (SHR) potently predicts adverse outcomes in patients with acute myocardial infarction (AMI), and previous studies reported U-shaped relationships between SHR and adverse prognosis. However, the relationship between SHR and mortality risk in AMI patients with or without atrial fibrillation (AF) remained unknown, and which factors affect the mortality in lower SHR patients were unclear. This study aims to research the relationship between SHR and mortality risk in AMI patients with or without AF, and whether AF affects the mortality in lower SHR patients., Methods: We conducted a cohort study using data from 3233 patients with a first diagnosis of AMI from the MIMIC-IV (version 2.2) database. Patients were divided into two groups based on AF. The study outcome was 1-year all-cause mortality. SHR was defined as the index calculated by the formula: SHR = (admission glucose) (mmol/L) / (1.59 * HbA1c [%] - 2.59)., Results: U-shaped association between SHR and all-cause mortality was found only in AMI patients with AF, not in AMI patients without AF. For AMI patients with AF, the inflection point for the curve was found to be a SHR of 1.09, either lower (OR, 0.30; 95%CI, 0.10, 0.94) or higher (OR, 3.28; 95%CI, 2.01, 5.34) SHR is associated with increased mortality. However, a linear relationship was found in patients without AF, higher (OR, 1.95; 95%CI, 1.52, 2.51) SHR is associated with increased mortality. For patients with SHR ≤ 1.09, AF increased the risk of all-cause mortality(OR, 1.50; 95%CI, 1.10, 2.05), while this effect was not found in patients with SHR > 1.09., Conclusion: The association between SHR and mortality in AMI patients with or without AF is different: U-shaped association between SHR and all-cause mortality only in AMI patients with AF, not in AMI patients without AF. AF is a factor that make the difference by increasing the risk of mortality in AMI patients with low SHR. Lower SHR may increase mortality through the onset of AF. This study emphasizes avoiding "relative hypoglycemia", SHR = 1.09 is the moderately tight glycemic control, which means glucose level is about (1.59 * HbA1c [%] - 2.59) * 1.09 mmol/L., Trial Registration: Clinical trial number: not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent from patients was not required as all protected private information was removed. As this is a retrospective observational study, Patients and/or the public were not directly involved in this study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Initial telomere length (TL) in newborns is the major determinant for TL in later life while TL in newborn/early-life predicts long-term health and lifespan. It is important to identify key factors that affect telomere homeostasis throughout embryonic development for precision interventions to maintain optimal TL in fetus/prenatal infants. SARS-CoV-2 has caused a widespread global pandemic of COVID-19, but it remains unclear whether maternal SARS-CoV-2 infection impairs prenatal telomere homeostasis., Methods: We recruited 413 normally delivered newborns whose mothers were either non-infected or infected with SARS-CoV-2 during different trimesters of pregnancy (otherwise healthy). Telomere length (TL) in cord blood (CB) was assessed using qPCR. CB and maternal blood were analyzed for cytokine levels. Placental senescence was determined using senescence-associated β-galactosidase staining., Results: Control (non-infected maternal) newborn TL was significantly longer than that from maternal infection (1.568 ± 0.340 vs 1.390 ± 0.350, P = 0.005). Such shorter TL was observed only if maternal infection of SARS-CoV-2 occurred in the first and second trimesters of pregnancy (1.261 ± 0.340 and 1.346 ± 0.353, P < 0.0001 and 0.001, respectively). There were no differences in TL between controls and infection at the third trimester (1.568 ± 0.340 vs 1.565 ± 0.329, P > 0.05). Across the first trimester, there was a positive correlation between newborn TL and gestational weeks with maternal infection, suggesting that the earlier maternal infection occurs, the worse effect is taken on fetal telomere homeostasis. Placental senescence coupled with the downregulated expression of telomerase reverse transcriptase was significantly more frequent from the maternal infection at the first trimester. There were no differences in IL-6, C reactive protein and other cytokine levels in CB and maternal serum or placentas., Conclusions: Maternal SARS-CoV-2 infection at the first and second trimesters leads to significantly shorter TL and earlier infection causes much more severe TL damage. The infection-mediated cell senescence and other histopathological abnormalities result in defective placental function through which fetal telomere homeostasis is impaired. Thus, vaccination against COVID-19 should be done in advance for women who plan pregnancy., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by Shandong Provincial Hospital Ethics Committees. The study was performed in accordance with the Declaration of Helsinki. Consent for publication: All authors agree to publish the manuscript. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence., Methods: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing. The pVACtools software suite of neoantigen prediction algorithms was used to identify and prioritize cancer neoantigens and facilitate vaccine design for manufacture in an academic GMP facility. Neoantigen DNA vaccines were administered via electroporation in the adjuvant setting (i.e., following surgical removal of the primary tumor and completion of standard of care therapy). Vaccines were monitored for safety and immune responses via ELISpot, intracellular cytokine production via flow cytometry, and TCR sequencing., Results: Eighteen subjects received three doses of a neoantigen DNA vaccine encoding on average 11 neoantigens per patient (range 4-20). The vaccinations were well tolerated with relatively few adverse events. Neoantigen-specific T cell responses were induced in 14/18 patients as measured by ELISpot and flow cytometry. At a median follow-up of 36 months, recurrence-free survival was 87.5% (95% CI: 72.7-100%) in the cohort of vaccinated patients., Conclusion: Our study demonstrates neoantigen DNA vaccines are safe, feasible, and capable of inducing neoantigen-specific immune responses., Clinical Trial Registration Number: NCT02348320., Competing Interests: Declarations Ethics approval and consent to participate The clinical protocol was reviewed and approved by the Institutional Review Board (ID# 201505074) at Washington University School of Medicine. The research conformed to the principles of the Helsinki/Tokyo/Venice Declaration on experimentation in humans. Consent for publication Written consent for publication was obtained from all participating patients. Competing interests K.S., M.G., and O.G. are consultants for the Jaime Leandro Foundation. All other authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Advance care planning (ACP) is pivotal in mitigating end-of-life suffering and ensuring healthcare congruence with the values of older adults and dignity in death. Despite its paramount importance, the current readiness for ACP among community-dwelling older adults and the intricate influencing factors have yet to be explored., Objective: To review the literature focusing on ACP readiness among community-dwelling older adults and the influencing factors., Methods: A scoping review conducted using the Arksey and O'Malley (2005) framework. Electronic databases (PubMed, CINAHL, Cochrane, Web of Science, PsycINFO), as well as grey literature databases (OpenGrey and GreyLit.org) were searched to identify studies published in English between January 2012 and March 2023., Results: 19 studies were selected, comprising 3 qualitative, 13 quantitative, 2 mixed-methods, and 1 review article. The study evaluated the readiness of older adults for ACP by examining their knowledge and attitudes. It categorizes influencing factors into intrinsic and extrinsic levels. This review revealed that the knowledge about ACP among older adults across all settings was limited. However, they had positive attitudes toward it. In addition, intrinsic factors including sociodemographic characteristics, psychological factors, and family relationships, along with extrinsic factors including health care professionals' attitudes and experience, as well as policies and laws, influenced the ACP readiness among older adults., Conclusions: This study established the groundwork for future ACP intervention trials, providing a theoretical framework to guide their design and implementation. operationalization., (© 2024. The Author(s).)

Background: Triple negative breast cancer (TNBC) represents a particularly aggressive and clinically challenging subtype of breast cancer, characterized by its invasive nature and generally poor prognosis. Treatment options for unresectable TNBC are limited. In recent years, the advent of PD-1/PD-L1 immune checkpoint inhibitors has offered a promising new treatment option for unresectable TNBC. The role of PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in unresectable TNBC management remains a subject of debate. This article aims to synthesize evidence from randomized controlled trials (RCTs) through a meta-analysis (MA) to provide a comprehensive evaluation of the efficacy and safety profile of ICIs in the treatment of unresectable TNBC., Method: We searched PubMed, Embase, Cochrane library, Web of Science, and ClinicalTrials.gov for the eligible RCTs which compared the efficacy and safety of PD-1/PD-L1 ICIs and chemotherapy alone. The outcomes analyzed included overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse effects (AEs)., Results: This meta-analysis included 11 trials. Therapy with PD-L1 inhibitors was superior to chemotherapy in terms of OS in both the intention-to-treat (ITT) population and the PD-L1-positive population. (ITT: HR: = 0.90 [0.81, 0.99], P = 0.04, I 2  = 48%; PD-L1 + : HR = 0.82 [0.70, 0.95], P = 0.01, I 2  = 64%); In terms of PFS, treatment with PD-L1 inhibitors prolonged PFS in both the ITT and PD-L1-positive populations compared with chemotherapy (ITT: HR: = 0.85 [0.77, 0.93], P = 0.0006, I 2  = 46%; PD-L1 + : HR = 0.72 [0.62, 0.83], P < 0.00001, I 2  = 70%, Fig. 5); Compared with chemotherapy alone, treatment with PD-1 inhibitors prolonged OS in both the PD-L1-positive and ITT populations. (ITT: HR = 0.87 [0.78, 0.96], P = 0.007, I 2  = 71%; CPS ≥ 1: HR = 0.81 [0.71, 0.92], P = 0.001, I 2  = 39%); In terms of PFS, therapy with PD-1 inhibitors improved PFS in both the ITT population and the PD-L1-positive population compared with chemotherapy. (ITT: HR = 0.79 [0.70, 0.90], P = 0.0004, I 2  = 0%; CPS ≥ 1: HR = 0.71 [0.61, 0.83], P < 0.0001, I 2  = 0%; CPS ≥ 10: HR = 0.67 [0.53, 0.84], P = 0.0008, I 2  = 0%)., Conclusion: Both PD-1 and PD-L1 inhibitors can offer survival benefits to TNBC patients, with the primary beneficiaries being those who are PD-L1-positive. However, immunotherapy can also lead to an increase in treatment-related adverse events. Therefore, it is essential to conduct a risk assessment for each patient before starting treatment to prevent the occurrence of serious adverse reactions., Trial Registration: This systematic review study has been filed with PROSPERO (Registration number: CRD42024571775)., (© 2024. The Author(s).)

Intestinal stem cells (ISCs) are responsible for intestinal homeostasis and are important for the regeneration of damaged intestine. We established an ionizing radiation (IR)-induced intestinal injury model and observed that Gelsolin KO mice had increased radiosensitivity. The deletion of Gelsolin aggravated intestinal damage and reduced the number of ISCs after lethal IR. The intestinal organoid experiments showed that Gelsolin deletion inhibited ISCs function after IR. Notably, RNA sequencing and RT-PCR results showed IL-17 signaling pathway was down-regulated and Th17 cells differentiation was inhibited in Gelsolin KO mice. Moreover, recombinant IL-17 A ameliorated IR-induced intestinal injury and promoted ISCs regeneration. To figure out the role of Gelsolin in Th17 cells differentiation, flow cytometry was used and we found that Gelsolin targets Th17 cells functionality via the p-STAT3/RORγt axis. By establishing the co-culture system, we proved that Th17 cells promoted self-renewal and budding abilities in Gelsolin-deficient organoids. Finally, we found that Gelsolin was protective against DSS-induced colitis and that this protective effect was not specific or limited to the IR induced intestinal injury model. Based on these results, we proved Gelsolin maintained the regeneration of ISCs by sustaining Th17 cells functions via the p-STAT3/RORγt axis., (© 2024. The Author(s).)

Background: In the face of family stress and emerging family problems, the transactional model of stress and coping provides new perspectives for solving stress problems in the family. This study integrates it with the common fate model to reveal new paths for coping with educational anxiety problems from the level of parent-child dichotomous interaction in the family environment, aiming to provide some theoretical and practical support for alleviating parents' education anxiety., Methods: This study used a combination of interviews and questionnaires to stratify students and their parents from a public junior high school in Jinan City to participate in the study. Data were collected in two time periods (T1, T2; one year apart), and the demographic characteristics of parents and children, parent-child communication quality, education anxiety, and parent-child trust relationship of 495 families were finally analysed by SPSS 27.0., Results: The results found that (1) based on the Common Fate Model, quality of parent-child communication negatively predicted parents' education anxiety; (2) quality of parent-child communication positively predicted parent-child trust relationship; (3) parent-child trust relationship negatively predicted parents'education anxiety; (4) parent-child trust relationship mediated quality of parent-child communication and education anxiety., Conclusions: This study sheds light on research related to stress coping and anxiety relief in the family environment, and provides theoretical and practical support for understanding the interaction between parents and children at the family level, and coping with stressful events together. It implies that future researchers should not only focus on one aspect when coping with and dealing with family problems, but should analyse the family as a whole, including the communication status and parent-child relationship between parents and children., (© 2024. The Author(s).)

Repair of the damaged meniscus is a scientific challenge owing to the poor self-healing potential of the white area of the meniscus. Tissue engineering provides a new method for the repair of meniscus injuries. In this study, we explored the superiority of 2% hyaluronic acid chitin hydrogel in temperature sensitivity, in vitro degradation, biocompatibility, cell adhesion, and other biological characteristics, and investigated the advantages of hyaluronic acid (HA) and Transforming Growth Factor β1 (TGF-β1) in promoting cell proliferation and a matrix formation phenotype. The hydrogel loaded with HA and TGF-β1 promoted cell proliferation. The HA + TGF-β1 mixed group showed the highest glycosaminoglycan (GAG) content and promoted cell migration. Hydroxypropyl chitin (HPCH), HA, and TGF-β1 were combined to form a composite hydrogel with a concentration of 2% after physical cross-linking, and this was injected into a rabbit model of a meniscus full-thickness tear. After 12 weeks of implantation, the TGF-β1 + HA/HPCH composite hydrogel was significantly better than HPCH, HA/HPCH, TGF-β1 + HPCH, and the control group in promoting meniscus repair. In addition, the new meniscus tissue of the TGF-β1 + HA/HPCH composite hydrogel had a tissue structure and biochemical content similar to that of the normal meniscus tissue., (© 2024. The Author(s).)

Photothermal therapy (PTT) is a promising non-invasive treatment that has shown great potential in eliminating tumors. It not only induces apoptosis of cancer cells but also triggers immunogenic cell death (ICD) which could activate the immune system against cancer. However, the immunosuppressive tumor microenvironment (TIME) poses a challenge to triggering strong immune responses with a single treatment, thus limiting the therapeutic effect of cancer immunotherapy. In this study, dual-targeted nano delivery system (GOx@FeNPs) combined with αPD-L1 immune checkpoint blocker could inhibit colorectal cancer (CRC) progression by mediating PTT, ferroptosis and anti-tumor immune response. Briefly, specific tumor delivery was achieved by the cyclic arginine glycyl aspartate (cRGD) peptide and anisamide (AA)  in GOx@FeNPs which not only had a good photothermal effect to realize PTT and induce ICD, but also could deplete glutathione (GSH) and catalyze the production of reactive oxygen species (ROS) from endogenous H 2 O 2 . All these accelerated the Fenton reaction and augmented the process of PTT-induced ICD. Thus, a large amount of tumor specific antigen was released to stimulate the maturation of dendritic cells (DCs) in lymph nodes and enhance the infiltration of CD8 + T cells in tumor. At the same time, the combination with αPD-L1 has favorable synergistic effectiveness against CRC with tumor inhibition rate over 90%. Furthermore, GOx@FeNPs had good magnetic resonance imaging (MRI) capability under T2-weighting owing to the presence of Fe 3+ , which is favorable for integrated diagnosis and treatment systems of CRC. By constructing a dual-targeted GOx@FeNPs nanoplatform, PTT synergistically combined with ferroptosis was realized to improve the immunotherapeutic effect, providing a new approach for CRC immunotherapy., (© 2024. The Author(s).)

Background: Diabetic retinopathy (DR) is a major ocular complication of diabetes mellitus, and a significant cause of visual impairment and blindness in adults. Phosphoserine aminotransferase 1 (PSAT1) is an enzyme participating in serine synthesis, which might improve insulin signaling and insulin sensitivity. Furthermore, it has been reported that the m6A methylation in mRNA controls gene expression under many physiological and pathological conditions. Nevertheless, the influences of m6A methylation on PSAT1 expression and DR progression at the molecular level have not been reported., Methods: High-glucose (HG) was used to treat human retinal pigment epithelial cells (ARPE-19) to construct a cell injury model. PSAT1 and Methyltransferase-like 3 (METTL3) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). PSAT1, B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), and METTL3 protein levels were examined by western blot assay. Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and TUNEL assays. Reactive oxygen species (ROS), malondialdehyde (MDA), and Glutathione peroxidase (GSH-Px) levels were examined using special assay kits. Interaction between METTL3 and PSAT1 was verified using methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assay., Results: PSAT1 and METTL3 levels were decreased in DR patients and HG-treated ARPE-19 cells. Upregulation of PSAT1 might attenuate HG-induced cell viability inhibition and apoptosis and oxidative stress promotion in ARPE-19 cells. Moreover, PSAT1 was identified as a downstream target of METTL3-mediated m6A modification. METTL3 might improve the stability of PSAT1 mRNA via m6A methylation., Conclusion: METTL3 might mitigate HG-induced ARPE-19 cell damage partly by regulating the stability of PSAT1 mRNA, providing a promising therapeutic target for DR., (© 2024. The Author(s).)

Background: Chronic heat stress (CHS) is a detrimental environmental stressor with a negative impact on the meat quality of broilers. However, the underlying mechanisms are not fully understood. This study investigates the effects of CHS on long non-coding RNA (lncRNA) expression and muscle injury in broilers, with a focus on its implications for meat quality., Results: The results showed that CHS diminished breast muscle yield, elevated abdominal fat deposition, induced cellular apoptosis (P < 0.05), and caused myofibrosis. Transcriptomic analysis revealed 151 differentially expressed (DE) lncRNAs when comparing the normal control (NC) and HS groups, 214 DE lncRNAs when comparing the HS and PF groups, and 79 DE lncRNAs when comparing the NC and pair-fed (PF) groups. After eliminating the confounding effect of feed intake, 68 lncRNAs were identified, primarily associated with cellular growth and death, signal transduction, and metabolic regulation. Notably, the apoptosis-related pathway P53, lysosomes, and the fibrosis-related gene TGF-β2 were significantly upregulated by lncRNAs., Conclusions: These findings indicate that chronic heat stress induces cellular apoptosis and muscle injury through lncRNA, leading to connective tissue accumulation, which likely contributes to reduced breast muscle yield and meat quality in broilers., (© 2024. The Author(s).)

Background: Plerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni., Methods: In this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults., Results: A total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni., Conclusions: The dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni., (© 2024. The Author(s).)

The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e-h + ) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi 2 S 3 -Bi 2 O 3 -Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O 2 ) and converting it to a single-linear state of oxygen ( 1 O 2 ) via e-h + transfer. Secondly, they react with hydrogen peroxide (H 2 O 2 ) and water (H 2 O) in tumor to produce hydroxyl radicals (•OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors., (© 2024. The Author(s).)

Background: Although national policies in China are comprehensive and instructive, a wide disparity exists between different cities. The current status of public mental health services by region in China remains unclear. This study aimed to investigate policies related to public mental health services, the contact coverage of public mental health services and outcomes of service users., Methods: A cross-sectional study was carried out in Southern China, between April 2021 and March 2022.  Considering the geographical location, socioeconomic development levels, and prevalence of severe mental illness, four cities including Wuhan, Changsha, Guangzhou, and Shenzhen were selected. Relevant service providers were asked to report data on mental health policies and facility-related information, including mental health resources, registration rates of patients, management rates of patients, and medication rates of patients. Eligible patients were invited to report service user-related data, including contact coverage of public mental health services and their outcomes. SPSS 26.0 was used for data analysis., Results: The four cities in Southern China have made different efforts to develop public mental health services, primarily focusing on socio-economically disadvantaged individuals. Community health centers in Guangzhou and Shenzhen reported having more professional human resources on mental health and higher mental health budgets for patients. The contact coverage rates of most public mental services were higher than 80%. Patients in Changsha (B = 0.3; 95%CI: 0.1-0.5), Guangzhou (B = 0.2; 95%CI: 0.1-0.3), and Shenzhen (B = 0.3; 95%CI: 0.1-0.4) who received social medical assistance services reported higher levels of medication adherence. Patients in Wuhan (B = -6.5; 95%CI: -12.9--0.1), Guangzhou (B = -2.8; 95%CI: -5.5--0.1), and Shenzhen who received community-based rehabilitation services reported lower levels of disability (B = -2.6; 95%CI: -4.6--0.5)., Conclusions: There have been advances in public mental health services in the four Southern cities. The contact coverage rates of most public mental health services were higher than 80%. Patients' utilization of public mental services was associated with better health outcomes. To improve the quality of public mental health services, the government should try to engage service users, their family members, and supporters in the design, delivery, operationalization, and evaluation of these public mental health services in the future., (© 2024. The Author(s).)

Background: Grafting with dwarf rootstock is an efficient method to control plant height in fruit production. However, the molecular mechanism remains unclear. Our previous study showed that plants with Prunus mume (mume) rootstock exhibited a considerable reduction in plant height, internode length, and number of nodes compared with Prunus persica (peach) rootstock. The present study aimed to investigate the mechanism behind the regulation of plant height by mume rootstocks through transcriptomic and metabolomic analyses with two grafting combinations, 'Longyan/Mume' and 'Longyan/Peach'., Results: There was a significant decrease in brassinolide levels in plants that were grafted onto mume rootstocks. Plant hormone signal transduction and brassinolide production metabolism gene expression also changed significantly. Flavonoid levels, amino acid and fatty acid metabolites, and energy metabolism in dwarf plants decreased. There was a notable upregulation of PmLBD3 gene expression in plant specimens that were subjected to grafting onto mume rootstocks. Auxin signalling cues promoted PmARF3 transcription, which directly controlled this upregulation. Through its binding to PmBAS1 and PmSAUR36a gene promoters, PmLBD3 promoted endogenous brassinolide inactivation and inhibited cell proliferation., Conclusions: Auxin signalling and brassinolide levels are linked by PmLBD3. Our findings showed that PmLBD3 is a key transcription factor that regulates the balance of hormones through the auxin and brassinolide signalling pathways and causes dwarf plants in stone fruits., (© 2024. The Author(s).)

Background: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease that leads to multiple organ dysfunction. The advent of disease-modifying treatments makes the early diagnosis of SMA critical. Health information literacy is vital for obtaining, understanding, screening, and using health information. Considering the importance of early diagnosis and the challenges in obtaining accurate information on patients with SMA, this cross-sectional study assessed health information literacy among children with SMA and their caregivers in China., Methods: Interviews with the caregivers of 10 patients with SMA were conducted by neurologists specializing in SMA. A questionnaire for evaluating the level of health information literacy was further developed among 145 children with SMA aged 10.0-120.0 months, with the average age of 81.9 months, and their caregivers. Parameters, such as the age at the onset of the first symptom and time from recognition of the first symptom to diagnosis, were examined. Health information literacy was measured using four dimensions: cognition, search, evaluation, and application., Results: The average time from the first symptom to first medical consultation was 4.8 months, and that from the first symptom to diagnosis was 10.8 months. There is a significant delay from the onset of the initial symptoms to a definitive diagnosis. Thirty-five (24%) patients had poor while 26 (18%) had high health information literacy. The overall score for health information literacy was 69; the scores for health information cognition and application were 90 and 84, respectively. The scores for evaluation (61) and search (57) were low. Medical personnel were considered the most professional and credible sources of information. Additionally, search engines and patient organizations were the other two most important sources of health literacy., Conclusion: Patients with SMA and their caregivers had low levels of health information literacy. SMA information visibility and standardization need to be improved. Medical personnel with experience in the diagnosis and treatment of SMA and media should aim to share knowledge and increase the quality of life of those with SMA., (© 2024. The Author(s).)

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant syndrome caused by a germline mutation in the fumarate hydratase (FH) gene that manifests with cutaneous leiomyomas, uterine fibroids, and renal cell cancer (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is no standardized therapy for advanced HLRCC-RCC. In this study, we described a case of aggressive HLRCC in a 33-year-old female who exhibited a novel heterozygous germline insertion mutation in exon 8 of the FH gene (c.1126 C > T; p.Q376*). The patient underwent laparoscopic resection of the right kidney, but metastases appeared within 3 months after surgery. Histological staining of the resected tumor revealed high expression levels of programmed cell death-ligand 1 (PD-L1). Therefore, the patient was treated with immunotherapy. The patient achieved a partial response to immunotherapy, and the treatment of metastatic lesions has continued to improve. A thorough literature review pinpointed 76 historical cases of HLRCC-RCC that had undergone immunotherapy. From this pool, 46 patients were selected for this study to scrutinize the association between mutations in the FH gene and the effectiveness of immunotherapy. Our results indicate that immunotherapy could significantly improve the overall survival (OS) of patients with HLRCC-RCC. However, no influence of different mutations in the FH germline gene on the therapeutic efficacy of immunotherapy was observed. Therefore, our study suggested that immunotherapy was an effective therapeutic option for patients with HLRCC regardless of the type of FH germline mutation., (© 2024. The Author(s).)

Background: Hepatocellular carcinoma is a highly lethal tumor worldwide, and China has a correspondingly high incidence and mortality rate. For patients with unresectable hepatocellular carcinoma, the prognosis is often poor. The objective of this retrospective study was to investigate the effects of conversion therapies on these patients., Methods: The study included patients between the ages of 18 and 75 who were initially diagnosed with unresectable hepatocellular carcinoma and received conversion therapy. After completing surgery, the patients underwent pathological diagnosis, which showed complete necrosis. The study was conducted retrospectively at the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2019 to December 2021. The main objectives of the study were to evaluate the overall survival and recurrence-free survival., Results: A total of 60 patients who met the inclusion criteria were enrolled. The median age of the patients was 56.6 ± 9.5 years, and 85% of them were male. The one-year overall survival rate (OS) was 98.3%, and the three-year OS was 95.6%. The one-year recurrence-free survival rate (RFS) was 81.1%, and the three-year RFS was 71.4%. In subgroup analysis, there was no statistically significant difference in RFS between patients with BCLC stages 0-A and BCLC stages B-C (p = 0.296). Additionally, there was no statistically significant difference in RFS between patients who received postoperative new adjuvant therapy and those who did not (p = 0.324)., Conclusions: Conversion therapy followed by surgical resection could be a promising treatment for patients with initially unresectable hepatocellular carcinoma, and the prognosis is good with a pathological complete response., (© 2024. The Author(s).)

Background: PD-1/PD-L1 blockade has become a powerful method to treat malignant tumors. However, a large proportion of patients still do not benefit from this treatment, due to low tumor immunogenicity and low tumor penetration of the agents. Recently, neutrophil elastase has been shown to induce robust tumor immunogenicity, while the insufficient enzyme activity at the tumor site restricted its anti-tumor application. Here, we designed polyethyleneimine-modified neutrophil elastase (PEI-elastase) loaded with PD-L1small interfering RNA (PD-L1 siRNA) for improving enzymatic activity and delivering siRNA to tumor, which was expected to solve the above-mentioned problems., Results: We first demonstrated that PEI-elastase possessed high enzymatic activity, which was also identified as an excellent gene-delivery material. Then, we synthesized anti-tumor lipopolymer (P-E/S Lip) by encapsulating PEI-elastase and PD-L1siRNA with pH-responsive anionic liposomes. The P-E/S Lip could be rapidly cleaved in tumor acidic environment, leading to exposure of the PEI-elastase/PD-L1 siRNA. Consequently, PEI-elastase induced powerful tumor immunogenicity upon direct tumor killing with minimal toxicity to normal cells. In parallel, PEI-elastase delivered PD-L1siRNA into the tumor and reduced PD-L1 expression. Orthotopic tumor administration of P-E/S Lip not only attenuated primary tumor growth, but also produced systemic anti-tumor immune response to inhibit growth of distant tumors and metastasis. Moreover, intravenous administration of P-E/S Lip into mice bearing subcutaneous tumors leaded to an effective inhibition of established B16-F10 tumor and 4T1 tumor, with histological analyses indicating an absence of detectable toxicity., Conclusions: In our study, a protease-based nanoplatform was used to cooperatively provoke robust tumor immunogenicity and down-regulate PD-L1 expression, which exhibited great potential as a combination therapy for precisely treating solid tumors., (© 2024. The Author(s).)

Purpose: This aim of this study was to investigate the analgesic efficacy and safety of lesser occipital nerve combined with great auricular nerve block (LOGAB) for craniotomy via a suboccipital retrosigmoid approach., Methods: Patients underwent vestibular schwannoma resection via a suboccipital retrosigmoid approach were randomly assigned to receive ultrasound-guided unilateral LOGAB with 5 ml of 0.5% ropivacaine (LOGAB group) or normal saline (NSB group). Numeric rating scale (NRS) scores at rest and motion were recorded within 48 h after surgery. Mean arterial pressure (MAP), heart rate (HR), opioid consumption and other variables were measured secondly., Results: Among 59 patients who were randomized, 30 patients received ropivacaine, and 29 patients received saline. NRS scores at rest (1.8 ± 0.5 vs. 3.2 ± 0.8, P = 0.002) and at motion (2.2 ± 0.7 vs. 3.2 ± 0.6, P = 0.013) of LOGAB group were lower than those of NSB group within 48 h after surgery. NRS scores of motion were comparable except for 6th and 12th hour (P < 0.05) in the LOGAB group. In LOGAB group, MAP decreased significantly during incision of skin and dura (P < 0.05) and intraoperative opoid consumption was remarkably reduced (P < 0.01). Postoperative remedial analgesia was earlier in the NSB group (P < 0.001). No patients reported any adverse events., Conclusion: Among patients undergoing craniotomy for vestibular schwannoma via a suboccipital retrosigmoid approach, LOGAB may be a promising treatment for perioperative analgesia and has the potential to maintain intraoperative hemodynamic stability., Clinical Trial Registration Number: Chictr.org.cn ChiCTR2000038798., (© 2024. The Author(s).)

Background: Studies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear., Methods: The expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC., Results: TSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status., Conclusion: The effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies., (© 2024. The Author(s).)

Background: To establish a normative database for macular vessel density (VD) measured by optical coherence tomography angiography (OCTA) and explore the parameters related to the VD., Methods: An observational study in epidemiology. 5840 healthy elderly participants in Beichen district, Tianjin, China underwent detailed ophthalmic and systemic examinations. OCTA was performed in all subjects using a 6 × 6-mm line scan mode centered on the macula and the built-in software was used to quantify VD and stratify the retina., Results: One thousand four hundred sixty-one healthy elderly citizens (30.4% men) were included, with a median age of 60.0 years (8.0 years) and an age range of 50 to 87 years.VDs in the different plexuses: superficial capillary plexus (SCP) 43.9% (3.2%), deep capillary plexus (DCP) 44.3% (2.8%), outer capillary plexus (OCP) 21.9% (5.9%), choriocapillaris (CC) 52.1% (1.4%). 90% medical reference range of the VDs at different plexuses was reported. Age was correlated with the VDs of each capillary plexus. Sex was correlated with the VDs of DCP and OCP, and the VDs of DCP (p < 0.001) and OCP (p = 0.015) in women were higher than that in men. After age and sex adjustment, choroid average thickness was positively correlated with VDs of SCP (R = 0.067, p = 0.010) and DCP (R = 0.108, p < 0.001), ganglion cell layer (GCL) average thickness (R = 0.072, p = 0.006) was positively correlated with the VD of OCP, best-corrected visual acuity (BCVA) (R = 0.082, p = 0.002) was positively correlated with the VD of CC., Conclusions: In this study, the normative VD database of the Chinese urban healthy elderly population measured by the OCTA was established, and parameters related to the VD of each capillary plexus were analyzed, providing new ideas for the future study of the relationship between macular VD and disease., Trial Registration: The Beichen Eye Study had been registered on the Chinese Clinical Trial Registry website (registry number: ChiCTR2000032280) on April 25, 2020., (© 2024. The Author(s).)

Background: Patients requiring coronary artery bypass grafting (CABG) have multiple co-morbidities which need to be considered in totality when determining surgical risks. The objective of this study is to evaluate short-term and long-term mortality rates of CABG surgery, as well as to identify the most significant risk factors for mortality after isolated CABG., Methods: All patients with complete dataset who underwent isolated CABG between January 2008 and December 2017 were included. Univariate and multivariate Cox regression was performed to determine the risk factors for all-cause mortality. Classification and regression tree analysis was performed to identify the relative importance of these risk factors., Results: 3,573 patients were included in the study. Overall mortality rate was 25.7%. In-hospital mortality rate was 1.62% overall. 30-day, 1-year, 5-year, 10-year and 14.5-year mortality rates were 1.46%, 2.94%, 9.89%, 22.79% and 36.30% respectively. Factors associated with death after adjustment for other risk factors were older age, lower body mass index (BMI), hypertension, diabetes mellitus, chronic obstructive pulmonary disease, pre-operative renal failure on dialysis, higher last pre-operative creatinine level, lower estimated glomerular filtration rate (eGFR), heart failure, lower left ventricular ejection fraction and New York Heart Association class II, III and IV. Additionally, female gender and logistic EuroSCORE were associated with death on univariate Cox analysis, but not associated with death after adjustment with multivariate Cox analysis. Using CART analysis, the strongest predictor of mortality was pre-operative eGFR < 46.9, followed by logistic EuroSCORE ≥ 2.4., Conclusion: Poorer renal function, quantified by a lower eGFR, is the best predictor of post-CABG mortality. Amongst other risk factors, logistic EuroSCORE, age, diabetes and BMI had a relatively greater impact on mortality. Patients with chronic kidney disease stage 3B and above are at highest risk for mortality. We hope these findings heighten awareness to optimise current medical therapy in preserving renal function upon diagnosis of any atherosclerotic disease and risk factors contributing to coronary artery disease., (© 2024. The Author(s).)

Background: Bone defects, resulting from substantial bone loss that exceeds the natural self-healing capacity, pose significant challenges to current therapeutic approaches due to various limitations. In the quest for alternative therapeutic strategies, bone tissue engineering has emerged as a promising avenue. Notably, excretory proteins from Toxoplasma gondii (TgEP), recognized for their immunogenicity and broad spectrum of biological activities secreted or excreted during the parasite's lifecycle, have been identified as potential facilitators of osteogenic differentiation in human bone marrow mesenchymal stem cells (hBMSCs). Building on our previous findings that TgEP can enhance osteogenic differentiation, this study investigated the molecular mechanisms underlying this effect and assessed its therapeutic potential in vivo., Methods: We determined the optimum concentration of TgEP through cell cytotoxicity and cell proliferation assays. Subsequently, hBMSCs were treated with the appropriate concentration of TgEP. We assessed osteogenic protein markers, including alkaline phosphatase (ALP), Runx2, and Osx, as well as components of the BMP/Smad signaling pathway using quantitative real-time PCR (qRT-PCR), siRNA interference of hBMSCs, Western blot analysis, and other methods. Furthermore, we created a bone defect model in Sprague-Dawley (SD) male rats and filled the defect areas with the GelMa hydrogel, with or without TgEP. Microcomputed tomography (micro-CT) was employed to analyze the bone parameters of defect sites. H&E, Masson and immunohistochemical staining were used to assess the repair conditions of the defect area., Results: Our results indicate that TgEP promotes the expression of key osteogenic markers, including ALP, Runx2, and Osx, as well as the activation of Smad1, BMP2, and phosphorylated Smad1/5-crucial elements of the BMP/Smad signaling pathway. Furthermore, in vivo experiments using a bone defect model in rats demonstrated that TgEP markedly promoted bone defect repair., Conclusion: Our results provide compelling evidence that TgEP facilitates hBMSC osteogenic differentiation through the BMP/Smad signaling pathway, highlighting its potential as a therapeutic approach for bone tissue engineering for bone defect healing., (© 2024. The Author(s).)

Background: Omicron variants are currently the predominant circulating lineage worldwide and most cases are mild or asymptomatic. The Omicron variant is characterized by high transmissibility and immune evasion. Early identification of Omicron cases in clinical settings is crucial for controlling its spread. Previous studies have indicated that changes in hematological parameters can be used to predict the severity of coronavirus disease 2019 (COVID-19). However, the role of hematological parameters in non-severe and asymptomatic cases remains unknown. This study aimed to investigate the role of hematological parameters in non-severe and asymptomatic Omicron variant infections., Methods: Hematological parameters and results were analyzed and compared in symptomatic (n = 356) and asymptomatic (n = 171) groups respectively, and between these two groups with positive COVID-19 tests. The utility of hematological parameters for predicting positive COVID-19 tests was analyzed using receiver operating characteristic curves., Results: Individuals with non-severe cases exhibited decreased levels of platelets, lymphocytes, eosinophils, basophils, lymphocytes (%), eosinophils (%), and basophils (%), while exhibiting elevated counts of monocytes, neutrophils (%), monocytes (%), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) when compared to suspected cases or asymptomatic carriers. In asymptomatic patients, positive carriers had lower leukocyte, neutrophil, and lymphocyte counts but higher monocyte, monocyte (%), PLR, and CRP levels than negative carriers. Basophil counts combined with lymphocytes or the PLR demonstrated a more significant predictive value in screening non-severe cases earlier compared to other parameters. The combined assessment of the monocyte (%) and the PLR had the highest area under the curve for diagnosing asymptomatic carriers., Conclusions: Circulating basophils, alone or in combination with other hematological parameters, may be used as efficient biomarkers for early screening of non-severe Omicron cases., (© 2024. The Author(s).)

Background: Inflammation is a key driver of atherosclerotic diseases and is often accompanied by disease-related malnutrition. However, the long-term burden of dysregulated inflammation with superimposed undernutrition in patients with acute coronary syndrome (ACS) remains unclear. This study sought to investigate the double burden and interplay of inflammation and malnutrition in patients with ACS undergoing percutaneous Coronary Intervention (PCI)., Methods: We retrospectively included 1,743 ACS patients undergoing PCI from June 2016 through November 2017 and grouped them according to their baseline nutritional and inflammatory status. Malnutrition was determined using the nutritional risk index (NRI) with a score lower than 100 and a high-inflamed condition defined as hs-CRP over 2 mg/L. The primary outcome was major adverse cardiovascular events (MACEs), compositing of cardiac mortality, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Long-term outcomes were examined using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding. The reclassification index (NRI)/integrated discrimination index (IDI) statistics estimated the incremental prognostic impact of NRI and hs-CRP in addition to the Global Registry of Acute Coronary Events (GRACE) risk score., Results: During a median follow-up of 30 months (ranges 30-36 months), 351 (20.1%) MACEs occurred. Compared with the nourished and uninflamed group, the malnourished and high-inflamed group displayed a significantly increased risk of MACEs with an adjusted hazard ratio of 2.446 (95% CI: 1.464-4.089; P < 0.001). The prognostic implications of NRI were influenced by patients' baseline inflammatory status, as it was only associated with MACEs among those high-inflamed (P for interaction = 0.005). Incorporating NRI and hs-CRP into the GRACE risk score significantly improved its predictive ability for MACEs (NRI: 0.210, P < 0.001; integrated discrimination index; IDI: 0.010, P < 0.001) and cardiac death (NRI: 0.666, P < 0.001; IDI: 0.023, P = 0.002)., Conclusions: Among patients with ACS undergoing PCI, the double burden of inflammation and malnutrition signifies poorer outcomes. Their prognostic implications may be amplified by each other and jointly improve the GRACE risk score's risk prediction performance., (© 2024. The Author(s).)

Background: Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions., Methods: A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts., Results: The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis., Conclusions: In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes., (© 2024. The Author(s).)