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DNA/RNA methylation plays an important role in lung cancer initiation and progression. Liquid biopsy makes use of cells, nucleotides and proteins released from tumor cells into body fluids to help with cancer diagnosis and prognosis. Methylation of circulating tumor DNA (ctDNA) has gained increasing attention as biomarkers for lung cancer. Here we briefly introduce the biological basis and detection method of ctDNA methylation, and review various applications of methylated DNA in body fluids in lung cancer screening, diagnosis, prognosis, monitoring and treatment prediction. We also discuss the emerging role of RNA methylation as biomarkers for cancer. [ABSTRACT FROM AUTHOR]

Background: Helping cancer survivors to transition from active treatment to long-term survivorship requires coordinated efforts by both oncologists and primary care physicians (PCPs). This study aims to evaluate cancer survivors' perspectives on PCP-delivered survivorship care. Methods: We conducted an Internet-based cross-sectional survey of cancer survivors via www.OncoLink.org. Regression analyses were used to identify factors associated with perception of PCP-delivered survivorship care. Results: The 352 respondents rated overall PCP-delivered survivorship care as 60 out of 100 (SD = 23). The areas of care most strongly endorsed were general care (62 %), psychosocial support (65 %), and holistic care (68 %). Survivors were less likely to perceive their PCPs as knowledgeable about cancer follow-up (43 %), late or long-term effects of cancer therapy (45 %), and diagnosis and treatment of symptoms related to cancer or cancer therapy (42 %). While 72 % of survivors reported satisfaction with their PCP's care overall, only 41 % felt that their PCPs and oncologists communicated well with one another. In a multivariate regression analysis, higher trust in PCP (p < 0.001), non-white race (p = 0.001), living in the United States (p = 0.007), and visiting a PCP two or more times per year (p = 0.009) were significantly associated with higher ratings of PCP-delivered survivorship care. p Conclusions: While cancer survivors in general are satisfied with care delivery by PCPs, they perceived that their PCPs have limited abilities in performing cancer-specific follow-up and late effect monitoring and treatment. Better education of family physicians about survivorship issues and improved communication between PCPs and oncologists are needed to improve PCPs' delivery of survivorship care. [ABSTRACT FROM AUTHOR]

Introduction: Arthralgia is a common toxicity among women taking aromatase inhibitors (AIs) and can lead to premature discontinuation of therapy. We evaluated the association between arthralgia, co-morbid fatigue and/or insomnia, and inflammatory biomarkers among women taking AIs. Methods: Women taking AIs for early-stage breast cancer completed a modified version of the Brief Pain Inventory, the Brief Fatigue Inventory, and the Insomnia Severity Index and provided blood samples for simultaneous assessment of 34 inflammatory biomarkers with a Luminex kit. Two-sided t tests were used to compare inflammatory biomarker concentrations for patients with or without moderate to severe arthralgia. Multivariate linear regression analyses were performed to evaluate the relationship between comorbid arthralgia, fatigue, and insomnia with identified biomarker concentrations. Results: Among 203 participants, the severity of arthralgia, fatigue, and insomnia were significantly correlated with each other (p < 0.001 for all comparisons). After controlling for race, chemotherapy history, non-steroidal anti-inflammatory drug use, age, and body mass index, the coexistence of arthralgia, fatigue, and insomnia was associated with elevated C-reactive protein (CRP) (β = 93.1; 95 % confidence interval (CI): 25.1-161.1; p = 0.008), eotaxin (β = 79.9; 95 % CI: 32.5-127.2; p = 0.001), monocyte chemoattractant protein (MCP)-1 (β = 151.2; 95 % CI: 32.7-269.8; p = 0.013), and vitamin D-binding protein (VDBP) (β = 19,422; 95 % CI: 5500.5-33,344; p = 0.006). Conclusions: Among women taking AIs, the coexistence of arthralgia, fatigue, and insomnia was associated with increased levels of inflammatory biomarkers (elevated CRP, eotaxin, MCP-1, and VDBP). These findings suggest a possible shared inflammatory mechanism underlying these common symptoms. [ABSTRACT FROM AUTHOR]

Introduction Telomere length (TL) is a biomarker of accumulated cellular damage and human aging. Evidence in healthy populations suggests that TL is impacted by a host of psychosocial and lifestyle factors, including physical activity. This is the first study to evaluate the relationship between self-reported physical activity and telomere length in early stage breast cancer survivors. Methods A cross-sectional sample of 392 postmenopausal women with stage I-III breast cancer at an outpatient oncology clinic of a large university hospital completed questionnaires and provided a blood sample. TL was determined using terminal restriction fragment length analysis of genomic DNA isolated from peripheral blood mononuclear cells. Physical activity was dichotomized into two groups (none versus moderate to vigorous) using the International Physical Activity Questionnaire. Multivariate linear and logistic regression analyses were performed to identify factors associated with mean TL and physical activity. Results Among participants, 66 (17%) did not participate in any physical activity. In multivariate model adjusted for age, compared to those who participated in moderate to vigorous physical activity, women who participated in no physical activity had significantly shorter TL (adjusted coefficient β = -0.22; 95% confidence interval (CI), -0.41 to -0.03; P = .03). Nonwhite race, lower education and depressive symptoms were associated with lack of self-reported physical activity (P < 0.05 for all) but not TL. Conclusion Lack of physical activity is associated with shortened TL, warranting prospective investigation of the potential role of physical activity on cellular aging in breast cancer survivors. [ABSTRACT FROM AUTHOR]

Background As breast cancer patients increasingly use complementary and alternative medicine (CAM), clinical trials are needed to guide appropriate clinical use. We sought to identify sociodemographic, clinical and psychological factors related to willingness to participate (WTP) and to determine barriers to participation in an acupuncture clinical trial among breast cancer patients. Methods We conducted a cross-sectional survey study among post-menopausal women with stage I-III breast cancer on aromatase inhibitors at an urban academic cancer center. Results Of the 300 participants (92% response rate), 148 (49.8%) reported WTP in an acupuncture clinical trial. Higher education (p = 0.001), increased acupuncture expectancy (p < 0.001), and previous radiation therapy (p = 0.004) were significantly associated with WTP. Travel difficulty (p = 0.002), concern with experimentation (p = 0.013), and lack of interest in acupuncture (p < 0.001) were significant barriers to WTP. Barriers differed significantly by socio-demographic factors with white people more likely to endorse travel difficulty (p = 0.018) and non-white people more likely to concern with experimentation (p = 0.024). Older patients and those with lower education were more likely to report concern with experimentation and lack of interest in acupuncture (p < 0.05). Conclusions Although nearly half of the respondents reported WTP, significant barriers to participation exist and differ among subgroups. Research addressing these barriers is needed to ensure effective accrual and improve the representation of individuals from diverse backgrounds. [ABSTRACT FROM AUTHOR]

Background: Premature discontinuation of aromatase inhibitors (AIs) in breast cancer survivors compromises treatment outcomes. We aimed to evaluate whether patient-reported joint pain predicts premature discontinuation of AIs.Methods: We conducted a retrospective cohort study of postmenopausal women with breast cancer on AIs who had completed a survey about their symptom experience on AIs with specific measurements of joint pain. The primary outcome was premature discontinuation of AIs, defined as stopping the medication prior to the end of prescribed therapy. Multivariate Cox regression modeling was used to identify predictors of premature discontinuation.Results: Among 437 patients who met eligibility criteria, 47 (11%) prematurely discontinued AIs an average of 29 months after initiation of therapy. In multivariate analyses, patient-reported worst joint pain score of 4 or greater on the Brief Pain Inventory (BPI) (Hazard Ratio [HR] 2.09, 95% Confidence Interval [CI] 1.14-3.80, P = 0.016) and prior use of tamoxifen (HR 2.01, 95% CI 1.09-3.70, P = 0.026) were significant predictors of premature discontinuation of AIs. The most common reason for premature discontinuation was joint pain (57%) followed by other therapy-related side effects (30%). While providers documented joint pain in charts for 82% of patients with clinically important pain, no quantitative pain assessments were noted, and only 43% provided any plan for pain evaluation or management.Conclusion: Worst joint pain of 4 or greater on the BPI predicts premature discontinuation of AI therapy. Clinicians should monitor pain severity with quantitative assessments and provide timely management to promote optimal adherence to AIs. [ABSTRACT FROM AUTHOR]

Introduction: Aromatase inhibitor-associated arthralgia (AIAA) is a common and often debilitating symptom in breast cancer survivors. Since joint symptoms have been related to estrogen deprivation through the menopausal transition, we hypothesized that genetic polymorphisms in CYP19A1, the final enzyme in estrogen synthesis, may be associated with the occurrence of AIAA. Methods: We performed a cross-sectional study of postmenopausal women with stage 0 to III breast cancer receiving adjuvant aromatase inhibitor (AI) therapy. Patient-reported AIAA was the primary outcome. DNA was genotyped for candidate CYP19A1 polymorphisms. Serum estrogen levels were evaluated by radioimmunoassay. Multivariate analyses were performed to examine associations between AIAA and genetic variants controlling for possible confounders. Results: Among 390 Caucasian participants, 50.8% reported AIAA. Women carrying at least one 8-repeat allele had lower odds of AIAA (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.21 to 0.79, P = 0.008) after adjusting for demographic and clinical covariates. Estradiol and estrone were detectable in 47% and 86% of subjects on AIs, respectively. Although these post-AI levels were associated with multiple genotypes, they were not associated with AIAA. In multivariate analyses, women with more recent transition into menopause (less than five years) were significantly more likely to report AIAA than those greater than ten years post-menopause (AOR 3.31, 95% CI 1.72 to 6.39, P < 0.001). Conclusions: Functional polymorphism in CYP19A1 and time since menopause are associated with patientreported AIAA, supporting the hypothesis that the host hormonal environment contributes to the pathophysiology of AAIA. Prospective investigation is needed to further delineate relationships between host genetics, changing estrogen levels and AIAA. [ABSTRACT FROM AUTHOR]

The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was downmodulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic. [ABSTRACT FROM AUTHOR]

Background: To investigate the feasibility, and safety of 125I seed permanent implantation for recurrent head and neck carcinoma under CT-guidance. Results: A retrospective study on 14 patients with recurrent head and neck cancers undergone 125I seed implantation with different seed activities. The post-plan showed that the actuarial D90 of 125I seeds ranged from 90 to 218 Gy (median, 157.5 Gy). The follow-up was 3 to 60 months (median, 13 months). The median local control was 18 months (95% CI, 6.1-29.9 months), and the 1-, 2-, 3-, and 5- year local controls were 52%, 39%, 39%, and 39%, respectively. The 1-, 2-, 3-, and 5- survival rates were 65%, 39%, 39% and 39%, respectively, with a median survival time of 20 months (95% CI, 8.7-31.3 months). Of all patients, 28.6% (4/14) died of local recurrence, 7.1% (1/ 14) died of metastases, one patient died of hepatocirrhosis, and 8 patients are still alive to the date of data analysis. Conclusion: CT-guided 125I seed implantation is feasible and safe as a salvage or palliative treatment for patients with recurrent head and neck cancers. [ABSTRACT FROM AUTHOR]

Background: The present study mainly aimed to investigate the direct effects of Endostar (ES) on the proliferation and radiosensitivity of human lung squamous cancer cell line H-520. Results: ES significantly inhibited H-520 cell proliferation in a time- and dose-dependent manner. According to the colony-forming assays, ES could increase the H-520 cell radiosensitivity. ES induced cell apoptosis, the apoptosis rate increased with the raise of ES concentration. Irradiation induced significantly higher apoptosis rate in ES-treated H-520 cells than non-treated H-520 cells. ES induced cell cycle distribution and G0/G1 arrest in H-520 cells, whereas irradiation induced G2/M arrest. The phospho-p38-MAPK and p-Akt protein levels were decreased in H-520 cells after ES treatment. Furthermore, activated caspase protein level increased and Bcl-2 protein levels decreased after treatment with ES and irradiation. Conclusion: ES significantly enhanced the sensitivity of H-520 cells to irradiation by inhibition of cellular proliferation, promotion of cell apoptosis and redistribution of cell cycle, possibly via deactivation of Akt pathway. The present study supports the possibility to use the combination of ES and ionizing irradiation to treat patients with lung squamous cell cancer in clinics. [ABSTRACT FROM AUTHOR]

The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic. [ABSTRACT FROM AUTHOR]

Background: The role of antithrombotic therapy in prognosticating patients with coronary heart disease (CHD) is crucial. This study evaluated the Knowledge, Attitude, and Practice (KAP) of CHD patients regarding antithrombotic therapy., Methods: This cross-sectional study distributed questionnaires to collect data. Participants' demographic information was recorded, and their KAP scores were assessed. The Self-Efficacy for Appropriate Medication Use Scale (SEAMS) measured self-efficacy., Results: The study comprised 639 individuals. The median scores were as follows: knowledge score 8 (IQR 6-10), attitude score 25 (IQR 23-27), and practice score 22 (IQR 20-24). Notably, up to 70% of patients incorrectly responded to questions about dosage and administration of antithrombotic agents, and approximately 40% lacked awareness of the treatment's importance and side effects. Low practice scores were independently linked to rural residence, low attitude scores, and poor self-efficacy. Furthermore, Predictive factors for low self-efficacy included being underweight, having a high family income, a short medical history, and low attitude scores., Conclusions: The surveyed patients with CHD exhibited good attitudes, practices, and self-efficacy but demonstrated only median knowledge levels toward antithrombotic therapy, especially about the importance and precautions associated with antithrombotic treatment. Therefore, initiatives aimed at improving adherence to antithrombotic therapy among CHD patients should focus on the knowledge gaps, especially for patients in rural areas. Improving the patient KAP could help improve the physician-patient interaction., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was granted by the Ethics Committee of Suzhou Municipal Hospital (Ethics Review Number: K-2023-097-K01), and informed consent was obtained from all participants. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: The intravitreal dexamethasone implant (Dex) is widely used for various ocular conditions, including diabetic macular edema (DME), retinal vein occlusion (RVO), and non-infectious uveitis. Despite its efficacy, concerns remain regarding its safety profile. This study aims to analyze the adverse events (AEs) associated with Dex reported in the FDA Adverse Event Reporting System (FAERS) database from 2010 to 2024., Methods: Data were extracted from FAERS, focusing on cases where Dex was the primary suspect drug. The dataset was processed to eliminate duplicates and incomplete entries. Disproportionality analysis, including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR), was used to detect safety signals. AEs were categorized by system organ class (SOC) and preferred term (PT)., Results: A total of 1,588 adverse event reports (AERs) were analyzed, revealing a significant upward trend. The Eye disorders was the most commonly reported SOC, with strong disproportionality signals (ROR: 45.11; PRR: 23.71). Key AEs identified at the PT level included Corneal decompensation, Choroidal hematoma, and Posterior capsule rupture, which were not listed on the drug label. Considering the reported numbers, the Endophthalmitis was the most common AE. Additionally, a significant proportion of AEs were observed within the first seven days post-administration, emphasizing the need for monitoring., Conclusion: While Dex remains an effective treatment option for ocular conditions, its use is associated with significant risks, particularly regarding unexpected and severe complications such as corneal decompensation. Continuous pharmacovigilance and detailed patient monitoring are essential to mitigate these risks. Future studies should focus on prospective designs and comprehensive clinical data to better understand the safety profile of Dex., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Pulmonary hypertension (PH) is a devastating disease marked by elevated pulmonary artery pressure, resulting in right ventricular (RV) failure and mortality. Despite the identification of several dysregulated genes in PH, the involvement of circular RNAs (circRNAs), a subset of long noncoding RNAs, remains largely unknown., Methods: In this study, high-throughput RNA sequencing was performed to analyze the genome-wide expression patterns of circRNAs in pulmonary arteries from three models of PH rats induced by hypoxia (Hyp), hypoxia/Sugen5416 (HySu), and monocrotaline (MCT). Differentially expressed circRNAs (DEcircRNAs) were identified, and a weighted gene coexpression network was constructed to explore circRNA networks associated with PH pathogenesis. A circRNA-miRNA-mRNA regulatory network was built, and the functional significance of targeted mRNAs was evaluated. Single-cell RNA sequencing provided insights into the distribution of cell type-specific circRNAs across PH progression., Results: Our analysis revealed 45 circRNAs exhibiting significant changes across all three PH rat models, with their host genes participating in the calcium signaling and muscle contraction. We identified 372 PH-related circRNA-miRNA-mRNA interactions, shedding light on the regulatory networks during PH development. Furthermore, we uncovered 186, 195 and 311 Hyp-, Hysu- and MCT-specific circRNAs, respectively. These circRNAs were enriched in distinct biological processes, emphasizing their unique regulatory roles. Single-cell spatial distribution analysis of these circRNAs in the pulmonary arteries of PH patients revealed that Hyp-specific circRNA predominantly appeared in the pulmonary vascular structural cells, while HySu- and MCT-specific circRNAs exhibited broader distribution, including significant enrichment in immune-related cells., Conclusion: Our study presents the first comprehensive view of circRNA regulatory networks in the pulmonary arteries of three PH rat models. We provide insights into PH-associated circRNAs, particularly their involvement in calcium signaling and muscle contraction., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments and related protocols were conducted in accordance with relevant guidelines and have been approved by the Animal Care and Use Committee of Shenzhen University (Ethical Approval Number: 2021003). All methods of animal experimentation in this study strictly adhered to the ARRIVE guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Safe prevention and control of plant viruses is a global challenge. Inducing viral capsid protein (CP) degradation via hydroxyl radicals (∙OH) generated by an in situ Fenton-like reaction within plant pathogenic tissues is proposed for combating plant viruses in this study. We designed a new Fenton-like reaction inducer, tCu inter -bCDs, which utilizes an internal doping strategy that reduces copper content by 89.89% compared to conventional doping methods, while still achieving a high coexistence of multivalent copper ions. Our research demonstrated that tCu inter -bCDs possessed functional activity to specifically recognize and proximally degrade CP. tCu inter -bCDs form complexes with CP monomers through supramolecular bonds characterized by significant electrostatic components. Within 10 min, the complex induced complete degradation of tertiary structure pockets composed of α-helices and β-sheets located at residues MET1-GLU23, TYR73-ARG93, and SER147-PRO157. Based on a high-resolution 2.91 Å CP model that was constructed for the first time, this degradation process is likely driven by hydrophobic interactions between tCu inter -bCDs and CP residues MET1, VAL5, THR55, and THR58, along with hydrogen bonds formed with THR4, VAL5, GLY15, PRO57, and ALA59, thereby promoting degradation of adjacent peptide segments. This represents the first study demonstrating in situ Fenton-like reactions to combat pathogens in plant systems. Our findings provide a new, efficient, and environmentally friendly approach for plant virus control., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Surgical management of giant and irregular pituitary neuroendocrine tumors (GIPitNETs) presents a significant challenge in neurosurgery. While endoscopic endonasal surgery (EES) is a widely used approach for PitNETs, GIPitNETs with extensive intracranial extension pose challenges for purely EES. We use simultaneous combined endoscopic endonasal and transcranial surgery (CECS) for the treatment of this type of tumor. Currently, there is limited research comparing CECS to EES for GIPitNETs. This study aims to compare the efficacy and short outcome of CECS and purely EES in the management of GIPitNETs to better understand the advantages and limitations of each surgical approach., Methods: The data of GIPitNETs patients who underwent surgery between March 2018 and May 2023 at a single center were retrospectively reviewed. All included cases were divided into CECS and EES groups according to the treatment modality received. The baseline characteristics and tumor imaging features of patients were compared between the groups, as well as surgical results, perioperative complications, and last follow-up outcomes., Results: A total of 50 patients met the inclusion criteria, with 27 undergoing CECS and 23 EES. CECS achieved a significantly higher GTR rate compared to EES (66.7% vs. 13.0%, p < 0.0001). CECS had longer operation times and hospital stays, but both approaches had similar rates of complications, including intracranial infection, CSF leakage, new pituitary dysfunction, postoperative diabetes insipidus, and vascular infarction. CECS reduces the risk of postoperative bleeding. Tumor recurrence and reoperation were significantly more common in the EES group., Conclusions: CECS is a safe and effective surgical approach for GIPitNETs, leading to higher rates of GTR, comparable complication rates, and reduced risk of postoperative bleeding when compared to purely EES. EES was associated with more tumor recurrence. Further long-term follow-up data is needed to validate these findings., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for this study was obtained from the first affiliated hospital of the Fujian Medical University ethics committee. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background and Objectives: Pb (lead) is a heavy metal, its carcinogenicity for bladder cancer is still debated, the link between blood lead levels (BLLs) and bladder cancer was investigated in this study., Methods: This cross-sectional study, using the NHANES (1999-2018) database, explored the relationship between BLLs and bladder cancer among Americans aged 20-85. It employed weighted multivariable logistic regression for analysis. Additionally, subgroup analyses and smoothed curve fitting were also performed., Results: This study included a total of 40,486 participants, the body mass index (BMI) of the participants is 28.71 ± 6.68 kg/m 2 . The average BLL is 0.0858 μmol/L (range: 0-2.96 μmol/L). A fully adjusted model showed that the BLL was associated with bladder cancer (odds ratio [OR] = 2.946, 95% confidence interval [CI] = 1.025 to 8.465, P = 0.047) in people with BMI < 28 kg/m 2 . However, no difference was found in the BMI ≥ 28 kg/m2 subgroup or in the general population. According to the subgroup analysis of participants with a BMI < 28 kg/m 2 , blood lead was associated with bladder cancer in the male, nonhypertensive, and < 70-year-old subgroups (p < 0.05) but no significantly different is observed in other subgroups. In addition, we discovered a nonlinear association between the BLLs and bladder cancer risk using a linear regression model., Conclusion: In this cross-sectional study, we found that the degree of correlation between BLLs and the risk of bladder cancer may vary among people with different BMIs. In people with BMI < 28 kg/m 2 , a higher BLL was independently associated with bladder cancer. However, more experiments are needed to confirm this finding., Competing Interests: Declarations. Ethics approval and consent to participate: The NCHS Research Ethics Review Board (ERB) approved the studies involving human participants. Informed consent was not required for this study in accordance with relevant national laws and institutional regulations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background and Objective: The classification of lumbar spondylolysis varies, and there is currently no clear consensus on a standardized system. This study examines the morphological characteristics and parameter differences of the L5 vertebra in patients with isolated versus fused spondylolysis using CT measurements. It also proposes a preliminary classification system based on the separation distance at the fracture site and explores its clinical significance., Methods: A total of 117 young male patients with L5 spondylolysis related to high-intensity physical activity were enrolled. Patients with a pars interarticularis separation distance ≥ 2 mm were classified into the isolated group (Group A, 66 patients), while those with a separation distance < 1 mm were classified into the fused group (Group B, 51 patients).Additionally, 117 patients without spondylolysis but experiencing lower back pain were included as the control group (group C). Multislice spiral computed tomography (MSCT) was used to measure the morphological parameters of the L5 vertebra in all three groups, including the sagittal pedicle height (SPH), transverse pedicle width (TPW), transverse pedicle vertical length (TPVL), pedicle screw trajectory length (PSTL), pedicle angle of attack (PAA), frontal vertebral body height (FVH), posterior vertebral body height (PVH), sagittal midline intervertebral space height (SMISH), horizontal vertebral body angle (HVA), and vertical vertebral body angle (VVA). Differences in the morphological imaging parameters of the L5 vertebrae and pedicles among the three groups were compared., Results: There were no significant differences in age, height, weight, body mass index (BMI), or Pfirrmann grade among the three groups. No significant differences were observed in any of the pedicle parameters between the left and right sides within the groups. Group A showed significantly greater TPVL and PSTL values compared to Group B, while TPW and PAA were significantly lower. No significant difference in SPH was observed between Group A and Group B. When compared to Group C, Group A exhibited significant differences in SPH, TPW, TPVL, and PSTL, but not in PAA. Group B, compared to Group C, demonstrated significant differences in SPH and PAA, but no significant differences were observed in TPW, TPVL, or PSTL. Significant differences were also found in FVH, HVA, and VVA between Group A and Group B, with Group A showing a smaller PVH. No significant difference in SMISH was observed between the two groups. Compared to Group C, Group A showed significant differences in PVH, HVA, and VVA, but no significant differences were found in FVH or SMISH. In Group B, significant differences were noted in FVH and HVA compared to Group C, but no differences were observed in PVH, SMISH, or VVA., Conclusion: Differences in the sagittal morphological parameters of the pedicles and vertebral bodies can be observed between the two types of spondylolysis patients. In the isolated spondylolysis pattern, the pedicles exhibit a "thin, long, and contracted" morphology, while the vertebral bodies present a "stuffed bun" shape, both anteriorly, posteriorly, and superiorly. In contrast, the fused type is characterized by "short, thick, and expanded" pedicles, with the vertebral bodies showing a "less pronounced stuffed bun" shape in the anterior-posterior direction. These morphological differences indicate that spondylolysis separation may involve adaptive stress-induced bone remodeling. Surgeons must pay special attention when choosing surgical techniques, as isolated spondylolysis may present a tendency toward slippage. Caution is advised in performing isolated pars repair surgeries, especially during the placement of pedicle screws, where special attention must be given to the length and direction of the screws to avoid additional damage., Competing Interests: Declarations. Ethics approval and consent to participate: This retrospective study was approved by the Ethics Committee of the General Hospital of Xinjiang Military Command and was carried out in accordance with the ethical standards set out in the Helsinki Declaration. Informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To investigate the characteristics and interrelationships between knowledge, preventive practice, and information sources of infectious diseases among Chinese children., Methods: This study used data collected from the baseline survey of a China national multi-centered cluster-randomized controlled trial in 2013. A total of 30,287 children completed a questionnaire package that included measures for knowledge, preventive practice and information sources related to infectious diseases., Results: The mean scores of knowledge and prevention practices of infectious diseases were 2.35 and 12.16, respectively. Children received information about infectious diseases primarily through school, other individuals, and electronic media. Knowledge and practices among children differed significantly across gender, age, single-child, living with parents or not, residence(urban/rural), regions, parental age and parents' education levels. Multivariable linear regression analysis showed that higher levels of knowledge(b = 0.102), and receiving information through schools(b = 0.054), electronic media(b = 0.016), and paper media(b = 0.054) were significantly associated with better preventive practice., Conclusions: Children's knowledge and various sources of access to information significantly predicted the prevention practice score. It might add value to future interventions and policy-making in promoting preventive measures for infectious diseases., Competing Interests: Declarations. Ethics approval and consent to participate: This study adhered to the STROBE guidelines, and received approval from the Medical Ethics Committee of Peking University Health Science Center (No.IRB0000105213034). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Sex determination mechanisms vary significantly across different chromosomal systems and evolutionary contexts. Nonetheless, the regulatory framework governing the multi-sex chromosome system (X 1 X 1 X 2 X 2 /X 1 X 2 Y) remains enigmatic. Through an examination of sex-related genes (dmrt1, hsd11b2, amh, sox9a, sox9b, foxl2, cyp19a), hormonal influences (E2, 11-KT), and histological analyses of gonadal development, we demonstrate that the critical period for sexual differentiation occurs between 35 to 60 days post-hatching (dph). Our multi-omics analysis identified amhr2 as a candidate sex-determining gene, revealing that the males possess three distinct amhr2 transcripts (amhr2ay, amhr2by, amhr2cy), whereas females express only one (amhr2a). In situ hybridization assays demonstrated that amhr2 is predominantly localized to primary spermatocyte and Sertoli cells of male testes. Notably, the specific mRNA expression of amhr2 is significantly enriched in amhr2cy, whose extracellular domain exhibits the highest binding affinity for Amh protein, with sexual expression differences manifesting as early as 5 dph. The outcomes of amhr2 interference (RNAi) experiments indicate that amhr2 knockdown leads to a reduction in the expression of male-related gene (dmrt1, amh, sox9a, sox9b), androgen synthesis genes (hsd11b2, cyp11a), and female-related genes (wnt4, foxl2, cyp19a, cyp19b). Conversely, overexpression of amhr2 yielded contrasting results. Our research supports the role of amhr2 as a pivotal candidate sex-determining gene. Furthermore, the dosage effect of amhr2, reflected in transcript abundance, mRNA expression levels, and binding efficacy, serves as a fundamental mechanism driving male differentiation and regulatory processes in Spotted knifejaw., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Laparoscopic radical resection has become the most important treatment for resectable colorectal cancer (CRC). However, there is still a lack of researches on the efficacy and safety of reduced-port laparoscopic surgery (RPLS) versus conventional laparoscopic surgery (CLS) in the treatment of CRC., Patients and Methods: From January 2019 to July 2022, 698 patients with CRC received surgical treatment in the Sixth Affiliated Hospital of Sun Yat-sen University were enrolled in this retrospective cohort study. Patients were divided into RPLS group (n = 220) and CLS group (n = 478) according to their surgical procedures. Propensity score matching (PSM) was used to adjust the differences in baseline characteristics. The incidence of perioperative outcomes and survival rates related results were analyzed after PSM., Results: Four hundred twenty-two patients were equally divided into RPLS group (n = 211) and CLS group (n = 211) after PSM. There were no statistically significant differences in overall survival (OS) and progression-free survival (PFS) between the two groups (P value was 0.773 and 0.579 respectively). The perioperative outcomes of patients between the two groups were comparable, except that patients in the RPLS group had a shorter postoperative hospital stay (P value < 0.001)., Conclusion: For patients with CRC, both RPLS and CLS might be acceptable surgical options. No significant differences in perioperative outcomes, PFS rates and OS rates were observed between the two groups. For certain cases, RPLS was superior to CLS in terms of postoperative recovery., Competing Interests: Declarations. Ethics approval and consent to participate: The experimental protocol was approved by the Central Ethics Committee of the Sixth Affiliated Hospital, Sun Yat-sen University (No. 2022ZSLYEC-335). Informed consent was not required due to the retrospective nature of the study. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To evaluate the ability to discriminate giant cell arteritis (GCA) from Takayasu arteritis (TAK) according to the modified 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) GCA classification criteria., Methods: Patients enrolled in the Japanese nationwide retrospective registry were evaluated using the criteria with partial modification; wall thickening of descending thoracic-abdominal aorta were mainly diagnosed by contrast-enhanced computed tomography (CT) or magnetic resonance imaging instead of evaluating with positron emission tomography (PET)-CT. The discriminability of the criteria was evaluated using C-statistic (> 0.7: good ability)., Results: Newly diagnosed patients with GCA (n = 139) and TAK (n = 129) were assessed, and 23.3% of TAK were aged 50 years or older at onset. The sensitivity of the modified 2022 ACR/EULAR GCA classification criteria with a score ≥ 6 was 82.0%, 68.5%, and 32.1% in all GCA, GCA with large-vessel involvement, and GCA without cranial arteritis, respectively. The specificity of the modified criteria was 96.1% for the 129 TAK as controls. Five patients with late-onset TAK met the modified criteria, and four had cranial signs and symptoms, two had bilateral axillary artery involvement, and four had descending thoracic-abdominal aorta involvement. The discriminability of the criteria was good (C-statistic: 0.986, 95% confidence interval [CI]: 0.976-0.996) and remained good after excluding age (C-statistic: 0.927, 95% CI: 0.894-0.961). The discriminability of a set of large-vessel lesions (bilateral axillary artery and descending thoracic-abdominal aorta) and inflammatory markers was markedly decreased with poor C-statistic value (C-statistic: 0.598, 95% CI: 0.530-0.667). Discriminability was improved after adding polymyalgia rheumatica (PMR) (C-statistic: 0.757, 95% CI: 0.700-0.813) or age (C-statistic: 0.913, 95%CI: 0.874-0.951) to the set of large-vessel lesions. In GCA patients with a score ≤ 5, 52% had bilateral subclavian and/or axillary artery involvement., Conclusion: The modified 2022 ACR/EULAR GCA classification criteria well performed in classifying GCA and TAK without PET-CT in routine clinical practice. A set of items included in the modified GCA classification criteria had good discriminative ability for GCA and TAK, even when age was excluded. However, age restriction or PMR was required to distinguish GCA without cranial lesions from TAK., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted following the Declaration of Helsinki and the Ethical Guidelines for Epidemiological Research in Japan. The institutional review board of Tokyo Medical and Dental University as the main center (approval number: M2000-2084-01) and the additional 23 institutions approved our retrospective study without personally identifiable information. Patients received posters informing the present study, or the posters were displayed in the outpatient clinic of each facility. Consent for publication: Not applicable. Competing interests: TS has received research grants from AsahiKASEI Co., Ltd., Daiichi Sankyo., Chugai Pharmaceutical Co., Ltd., and Ono Pharmaceutical. TS has received speaker’s fee from Abbvie Japan Co., Ltd., AsahiKASEI Co., Ltd., Astellas Pharma Inc., Ayumi Pharmaceutical, Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Mitsubishi-Tanabe Pharma Co., Ono Pharmaceutical, Pfizer Japan Inc., and Taisho Pharmaceutical Co., Ltd.. MH has received research grants from Boehringer-Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Teijin Pharma Ltd. MH has received speaker’s fee from Boehringer-Ingelheim Japan, Inc., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., and Teijin Pharma Ltd. MH is a consultant for Boehringer-Ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co., Ltd. and Teijin Pharma. HAU belongs to the Department of Chronic Kidney Disease and Cardiovascular Disease which is endowed by Olba Healthcare Holdings, Boehringer Ingelheim, and Terumo Corporation. HY has received lecture fees from Chugai Pharmaceutical and consulting fees from Janssen. HD has received speaking fees, and/or honoraria from Abbvie, Asahi Kasei Pharma, Astellas, UCB Pharmaceutical, Ayumi Pharmaceutical, GlaxoSmithKline, Novartis Pharma, Eli Lilly Japan, and AstraZeneca. YK has received speaker’s fee from GlaxoSmithKline. NT has received research grants from Asahi Kasei Pharma, Asahi Kasei Medical, Ayumi, AbbVie, Eisai, Nippon Boehringer Ingelheim, Taisho, Tanabe Mitsubishi, Chugai. NT has received speaker’s fee and/or consulting fee from Asahi Kasei Pharma, AstraZeneca, AbbVie, Eli Lilly Japan, GlaxoSmithKline, Chugai, Novartis, Bristol Myers Squibb, Janssen. YN has received consulting fees from AbbVie, Janssen Pharmaceutical KK, and Chugai, and has received lecture fees from AbbVie and Chugai. YM, JI and YW has nothing to declare., (© 2025. The Author(s).)

The orderly regulation of immune inflammation and promotion of the regeneration of skin vessels and fibers are key to the treatment of diabetic skin injury (DSI). Although various traditional polypeptide biological dressings continue to be developed, their efficacy is not satisfactory. In recent years, plant-to-mammal regulation has provided an effective approach for chronic wound management, but the development of effective plant-based treatments remains challenging. The development of exosomes from Chinese herbs is promising for wound healing. In this study, plant exosomes derived from lemons (Citrus limon) were extracted, and their biological efficacy was verified. Lemon exosomes regulated the polarization reprogramming of macrophages, promoted the proliferation and migration of vascular endothelial cells and fibroblasts, and thus promoted the healing of diabetic wounds. To solve the problems of continuous drug delivery and penetration depth, Lemon Exosomes were loaded into a hydrogel constructed of Gelatin Methacryloyl (GelMA) and Dialdehyde Starch (DAS) that closely fits to the skin, absorbs water, swells, and is moist and breathable, effectively promoting the sustained and slow release of exosomes and resulting in excellent performance for diabetic wound healing. Our GelMA-DAS-Lemon Exosomes hydrogel (GelMA/DAS/Exo hydrogel) patch represents a potentially valuable option for repairing diabetic wounds in clinical applications., Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were carried out in the Animal Experimental Center of Nanfang Hospital. All operations were trained, and the experimental protocol was reviewed and approved by the Ethics Committee of Southern Medical University. Consent for publication: All authors agree to be published. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Asthma and atopic dermatitis (AD) represent significant global health challenges in children. This study aimed to investigate trends in incidence, prevalence, and disability-adjusted life years (DALYs) for childhood asthma and AD from 1990 to 2021., Methods: The study utilized information from the Global Burden of Disease (GBD), Injuries, and Risk Factors Study 2021. The sample size for this study consisted of children with asthma or AD between the ages of 0 and 14. From 1990-2021, we calculated asthma and AD's age-standardized incidence, prevalence, and DALYs by area, age, sex, and socio-demographic index., Results: In 2021, global childhood asthma prevalence reached 95.7 million cases (age-standardized rate: 4,758 per 100,000), with the Low SDI region recording 25.4 million cases. For AD, global prevalence was 72.4 million cases (age-standardized rate: 3,600 per 100,000), predominantly in Middle SDI regions (19.7 million cases). Between 1990 and 2021, age-standardized incidence rates decreased for both conditions. Geographic variations were notable: High-income North America showed the highest asthma incidence, while Western Europe led in AD prevalence. The global burden of asthma-related DALYs declined from 6.9 million in 1990 to 4.6 million in 2021, with significant regional disparities., Conclusions: Despite decreasing age-standardized rates, childhood asthma and AD continue to pose substantial health burdens globally, with marked variations across regions and socioeconomic strata. These findings emphasize the need for targeted, region-specific interventions., Competing Interests: Declarations. Ethics approval and consent to participate: This study is based on data from the Global Burden of Disease (GBD) study. The GBD study uses deidentified data, and a waiver of informed consent was approved by the University of Washington Institutional Review Board. As our research utilized this publicly available, deidentified dataset, additional ethics approval for our specific analysis was not required. This approach is in line with the ethical guidelines for secondary data analysis. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Probiotics have been proposed as a potential strategy for managing ulcerative colitis (UC). However, the underlying mechanisms mediating microbiota-host crosstalk remain largely elusive. Here, we report that Limosilactobacillus reuteri (L. reuteri), as a probiotic, secretes cytoplasmic membrane vesicles (CMVs) that communicate with host cells, alter host physiology, and alleviate dextran sulfate sodium (DSS)-induced colitis. First, L. reuteri-CMVs selectively promoted the proliferation of the beneficial bacterium Akkermansia muciniphila (AKK) by upregulating the expression of glycosidases (beta-N-acetylhexosaminidase and alpha-N-acetylglucosaminidase) involved in glycan degradation and metabolic pathways and restored the disrupted gut microbiota balance. Second, L. reuteri-CMVs were taken up by intestinal epithelial cells (IECs), elevated the expression of ZO-1, E-cadherin (Cdh1), and Occludin (Ocln), decreased intestinal permeability, and exerted protective effects on epithelial tight junction functionality. RNA sequencing analysis demonstrated that L. reuteri-CMVs repaired intestinal barrier by activating the HIF-1 signaling pathway and upregulating HMOX1 expression. Third, L. reuteri-CMVs increased the population of double positive (DP) CD4 + CD8 + T cells in the intestinal epithelial layer, suppressing gut inflammation and maintaining gut mucosal homeostasis. Finally, L. reuteri-CMVs exhibited satisfactory stability and safety in the gastrointestinal tract and specifically targeted the desired sites in colitis mice. Collectively, these findings shed light on how L. reuteri interact with the host in colitis, and provide new insights into potential strategies for alleviating colitis., Competing Interests: Declarations. Ethics approval and consent to participate: All the animal experiments were approved by the Animal Care Committee of the Shenzhen People’s Hospital, Shenzhen, China (No. 2024-118). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The relationship between several inflammatory biomarkers and slow coronary flow phenomenon(SCFP) has been reported. However, the correlation between neutrophil percentage-to-albumin ratio (NPAR) and SCFP is lacking. In this study, we aimed to assess the relationship between NPAR and SCFP., Methods: A total of 228 patients were enrolled in this study according to the diagnostic and exclusion criteria. 76 patients were included in the SCFP group, and 152 age-matched patients were included in the normal coronary flow (NCF) group. The baseline data, laboratory parameters and coronary angiography were recorded and compared., Results: The values of NPAR were significantly higher in the SCFP group than those in the NCF group (1.78[1.58,1.88] vs. 1.42[1.24,1.66], P < 0.001). NPAR elevated as the number of vessels involved SCFP increased. In the multiple logistic regression tests, NPAR was an independent predictor of SCFP (OR: 1.239, 95%CI: 1.124-1.367, p < 0.001). The receiver operating characteristic curve analysis showed that the cutoff value of NPAR for predicting SCFP was > 1.57 with a 76.3% sensitivity and 67.1% specificity [the area under the curve (AUC) = 0.727, 95%CI: 0.659-0.795, p < 0.001]. NPAR had a better predictive value of SCFP than neutrophil percentage, but not albumin., Conclusion: Elevated NPAR may be an independent and valuable predictor of SCFP., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Ethics Committee of Suzhou Ninth Hospital affiliated to Soochow University (Decision no: KYLW2024-008‐01) and the study complied with the Declaration of Helsinki. Informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Osteosarcoma (OS) is a commonly observed malignant tumor in orthopedics that has a very poor prognosis. The endosomal sorting complex required for transport (ESCRT) is important for the development and progression of cancer and may be a significant target for cancer therapy. First, we built a prognostic signature using 7 ESCRT-related genes (ERGs) to predict OS patient prognosis. Analysis of internal and external datasets revealed that the ERG signature has good predictive ability and reproducibility. Immune analysis demonstrated a significant correlation between OS patient immune status and ERG signature score. Moreover, ERG signature score was found to be associated with the response of OS patients to immunotherapy and anticancer drugs. Additionally, we constructed a prognostic signature consisting of 10 ESCRT-related long noncoding RNAs (ERLs) that effectively predicted the prognosis of OS patients. Furthermore, two subgroups of OS patients with distinct prognoses (clusters 1 and 2) were identified. Finally, LMO7-AS1 was chosen for functional experimental validation. The knockdown of LMO7-AS1 suppressed the malignant progression of OS cells. Furthermore, transcriptome sequencing was performed on OS cells and revealed a correlation between LMO7-AS1 and the PI3K-Akt signaling pathway. In conclusion, our ESCRT transcriptome-associated signatures can act as prognostic biomarkers for OS, and LMO7-AS1 is a novel therapeutic target for the treatment of OS., Competing Interests: Declarations. Ethical approval: The animal experiment strictly followed the ARRIVE guidelines and approved by the Laboratory Animal Ethics Committee of Anhui Medical University. The ethical approval number is LLSC20241416. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Hypertensive Disorder during Pregnancy (HDP) is the most prevalent obstetric conditions in maternal health, but the etiology of most cases remains unexplained. Seasonal variations in the conception of HDP may offer insights into the potential seasonal-specific risk factors., Methods: Data were sourced from the China's National Maternal Near Miss Surveillance System (NMNMSS) between January 1, 2012, and December 31, 2021. HDP status was ascertained from the diagnostic records over 400 medical institutions. The conception date was estimated based on the delivery date and duration of gestation length, and the season of conception, were categorised as winter (December to February), spring (March to May), summer (June to August), and fall (September to November). Odd ratios were calculated separately using the logistic regression model., Results: Among the 14,073,565 pregnant women analysed, 3.98% met the study's criteria for HDP as defined in the present study. Maternal conception in spring was associated with a 10% increased risk of HDP (aOR, 1.10 [95% CI, 1.08-1.12]) compared with summer conceptions. Elevated risk of HDP was observed for maternal individuals conceiving in February, March, April, May, and June according to analyses conducted for specific months. The associations were slightly stronger in the subgroup of women diagnosed with gestational hypertension and preeclampsia. Significant disparities exist in this association among the diverse Köppen-Geiger climate zones., Conclusion: Significant seasonal variations in the risk for HDP were observed across a range of maternal characteristics, HDP subtypes, and climatc zones. These findings imply the necessity of considering seasonally fluctuating environmental factors in the etiological investigation of HDP., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee of West China Second University Hospital (Protocol ID: 2012008) and was deemed exempt from informed consent requirements owing to the lack of direct contact with the study population. Consent for publication: All authors have read and approved the submission of this manuscript, which has not been published previously and is not being considered for publication elsewhere, in whole or in part, in any language except as an abstract. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Objective: To investigate the effects of modified twin-block appliances (MTBA) on obstructive sleep apnea (OSA) and mandibular retrognathia and the changes in the upper airway, hyoid bone position, and hypoxia-related inflammatory marker levels in children with OSA., Methods: This study included children with OSA and mandibular retrognathia and those with class I without mandibular retrognathia (n = 35 each). The experimental group comprised children with OSA and mandibular retrognathia managed using MTBA. Postoperative and preoperative polysomnography, lateral cephalometric radiographs, and peripheral blood samples were collected. The control group comprised children with class I without mandibular retrognathia., Results: Following MTBA management, the experimental group exhibited decreased apnea-hypopnea index and increased lowest arterial oxygen saturation level (P < 0.05). Sella- and subspinale-nasion-supramental angles significantly increased and decreased, respectively (P < 0.05). Posterior soft palatal-posterior pharyngeal wall distance, apical palatal-middle pharyngeal wall distance, posterior airway space, epiglottis valley-hypopharyngeal wall distance, hyoid-prevertebral plane distance, and distance from the superior anterior point of the hyoid bone to the inferior anterior point of the third cervical spine significantly increased, whereas distance from the superior anterior point of the hyoid bone to the mandibular plane decreased (P < 0.05)., Conclusions: Children with OSA (n = 35) were managed using MTBA, which relieved the mandibular retrognathia deformity, widened the upper airway space, moved the hyoid bone forward and upward, and improved the sleep monitoring indicators. Thus, MTBA can achieve satisfactory therapeutic effect in children with OSA and mandibular retrognathia with mandibular advancement., Competing Interests: Declarations. Ethics approval and consent to participate: The project was approved by the Ethics Committee of the Children’s Hospital Affiliated to Chongqing Medical University. Approval Number: (2021)IRB(STUDY)NO.22.All procedures were performed in accordance with the ethical principles of the Helsinki declaration. Informed consents were obtained from all participants and their parents. Consent for publication: Not applicable. Clinical trial number: This study has been registered through the National Medical Research Registration and Archival Information system, and Clinical trial number is: MR-50-23-019230. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Patients with chronic obstructive pulmonary disease (COPD) and sarcopenia experience poorer clinical prognosis. Although sedentary behaviour (SB) is common risk factor for COPD, its relationship with sarcopenia in this specific population remains unclear., Methods: This is a cross-sectional survey of participants aged 40 and above with COPD, involving 27 communities and 2 hospitals' outpatient departments. The definition of sarcopenia was in accordance with the Asian Expert Consensus Criteria for sarcopenia. SB and physical activity (PA) were evaluated using the short form of the international physical activity questionnaires (IPAQ-SF). SB was categorized into 4 categories: less than 4 h/day, 4 to 6 h/day, 6 to 8 h/day, and 8 h or more per day. PA was classified into light-intensity and moderate-to-vigorous intensity physical activity (LPA and MVPA). Multiple logistic regression and restricted cubic spline (RCS) were performed to investigate the rates of association between sarcopenia and SB. Subgroups was analysed by gender., Results: A total of 414 COPD patients with complete information were included in this trial. The overall prevalence of sarcopenia was 22.9%. Participants with sarcopenia had longer of SB (P = 0.008) and less MVPA (P < 0.001) compared to those without sarcopenia. After adjustment for confounders, SB showed a significant association with sarcopenia (adjusted β = 1.47, 95% CI = 1.28-1.68). The participants who spent 6 or more hours on SB had a greater odds ratio for sarcopenia (= 6-8 h: adjusted OR = 2.97, 95% CI = 1.14-7.70; > 8 h: OR = 9.14, 95% CI = 3.59-23.22) than the participants who spent less than 4 h. The results of RCS indicated that when SB exceeded 5.7 h/day, a trend towards a significant increasing prevalence of sarcopenia was observed with increased SB. This trend was also observed across genders, differing only in the threshold values (male: SB = 5.7 h; female: SB = 8.0 h)., Conclusion: SB was an independent determinant of sarcopenia, independent of MVPA, and the prevalence of sarcopenia increases as SB increases within a certain range. This study advocated for the integration of SB in the self-management strategies for patients with COPD. Regardless of their engagement in MVPA, it was crucial to regulate SB., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committee of the School of Nursing and Rehabilitation, Shandong University, China (2019-R-022). Written informed consent was obtained from all participants before data collection. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: To analyze the effects of the positioning of a bolt in the femoral neck system (FNS) on the short-term outcomes of middle-aged and young adults with displaced femoral neck fractures (FNFs)., Methods: This was a retrospective study involving 114 middle-aged and young adults with displaced FNFs who were surgically treated with internal fixation via the FNS in the Department of Orthopedics, Suzhou Municipal Hospital, from December 2019 to January 2023. The degree of deviation of the central axis of the femoral head and neck from the tip of the bolt (W), the tip‒apex distance (TAD) and the length of femoral neck shortening (LFNS) were measured on postoperative X-ray and computed tomography (CT) scan images. Clinical efficacy was assessed with the Harris Hip Score (HHS) and the EuroQol five-dimensional questionnaire-5L (EQ-5D-5L) utility index. The enrolled patients were divided into the central group (W ≤ 20%) and deviation group (W > 20%) on the basis of postoperative W value. The quality of fracture reduction, time to postoperative weight-bearing of the affected limb, time to fracture healing, and the TAD, LFNS, HHS and EQ-5D-5L utility index at the last follow-up visit were compared between the groups. Postoperative complications and cases of revision surgery were recorded., Results: Preoperative baseline characteristics, the quality of fracture reduction, the need for auxiliary reduction and the follow-up time were comparable between the central group and deviation group (all P > 0.05). No significant difference in the time to postoperative partial weight-bearing of the affected limb was detected between the groups (P > 0.05). Patients in the central group presented with a significantly shorter time to full weight-bearing of the affected limb, time to fracture healing, and TAD and LFNS at the last follow-up visit but a greater HHS and EQ-5D-5L utility index than those in the deviation group did (all P < 0.05). The incidence of revision surgery was significantly lower in the central group than in the deviation group (P < 0.05)., Conclusion: Positioning of the FNS bolt closer to the central axis of the femoral head and neck favors a shorter time to fracture healing, greater hip function and a lower incidence of revision surgery in middle-aged and young adults with displaced FNFs., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in accordance with the principles of the Helsinki declaration of 1964 and its subsequent amendments. This study was approved by the Ethics Committee of Suzhou Municipal Hospital (No. KL901454). Informed consent was obtained from all the participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Emerging research found air pollution may be associated with incident Alzheimer's disease (AD) and other dementias. However, few studies have examined these associations at the global scale. This study aimed to assess the dynamic associations between ambient air pollution and the burden of AD and other dementias worldwide., Methods: This study synthesised 149 countries/territories between 1990 and 2019. These data include age-standardised mortality rate (ASMR) and disability-adjusted life-years (DALYs) of AD and other dementias, ambient air pollution (fine particulate matter [PM 2.5 ], NO 2 and O 3 concentration) and a series of covariates were from various source. Average annual percentage changes (AAPCs) were calculated to investigate the temporal variations. Linear mixed models were adopted to assess the associations with single- and multi-pollutant separately. The associations between air pollution changes and the AD and other dementias were also examined using linear regression models. Stratified analyses by Global North-South divide and human development index were performed to explore the potential inequity in air pollution impacts., Results: During 1990-2019, the global ASMR, DALYs and O 3 increased by 0.11%, 0.09%, and 0.17% per year, respectively. In contrast, PM 2.5 and NO 2 decreased by 0.33% and 0.14% per year, respectively. Each 10 µg/m 3 increase in PM 2.5 was associated with a 0.118 (95% confidence interval [CI]: 0.060 - 0.175) higher ASMR and 0.966 (95%CI: 0.321 - 1.611) higher DALYs after adjusting for all the covariates. The ASMR increased by 0.112 and the DALYs increased by 1.068 for each 10 µg/m 3 increase in O 3 . The NO 2 -dementia associations were relatively weak. Stronger O 3 -dementia associations were found in the Global South than those in the Global North., Conclusions: The burden of dementia is expected to increase globally, given the continuously expansion of the ageing population. Air pollution was found to be significantly associated with a higher burden of AD and dementia. As a persistent challenge in urban cities, air pollution demands strict regulatory control., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests. Conflict of interest: The authors declare that they have no conflicting interests related to this manuscript., (© 2025. The Author(s).)

Background: Fibrotic types of interstitial lung abnormalities seen on high-resolution computed tomography scans, characterised by traction bronchiolectasis/bronchiectasis with or without honeycombing, are predictors of progression and poor prognostic factors of interstitial lung abnormalities. There are no reports on the clinical characteristics of fibrotic interstitial lung abnormalities on high-resolution computed tomography scans. Therefore, we aimed to examine these clinical characteristics and clarify the predictive factors of fibrotic interstitial lung abnormalities on high-resolution computed tomography scans., Methods: Clinical and paraclinical data of 164 patients enrolled in the initial year of a multicentre prospective observational study (Kumamoto interstitial lung abnormalities study in Japan) involving over 62,000 examinees during routine health examinations were analysed. Clinical laboratory evaluations are expressed as medians and interquartile ranges for each evaluation time point, and boxplots were created for graphical representation. The percentages of abnormal clinical laboratory results were compared between the groups using chi-square or Fisher's exact tests. Univariate or multivariate logistic regression analyses were performed to analyse the relationship between fibrotic interstitial lung abnormalities and other clinical factors., Results: Fibrotic interstitial lung abnormalities were observed on high-resolution computed tomography scans in 135 (82%) patients at the time of diagnosis. Multivariate analysis showed that older age (Odds ratio, 1.06; 95% confidence interval, 1.01-1.12; p = 0.021), auscultatory fine crackles (Odds ratio, 3.39; 95% confidence interval, 1.33-8.65; p < 0.01), and elevated serum surfactant protein-D (Odds ratio, 2.68; 95% confidence interval, 1.02-8.64; p = 0.045) were independent predictive factors of fibrotic interstitial lung abnormalities. The predicted area under the curve of the fibrotic interstitial lung abnormalities based on these three factors was 0.77 (95% confidence interval, 0.68-0.86). The proportion of undecided diagnoses in the fibrotic interstitial lung abnormalities group (14%) was significantly lower than that in the non-fibrotic interstitial lung abnormalities group (41%) (p = 0.0027)., Conclusions: Fine crackles on auscultation and elevated serum surfactant protein-D levels are predictors of fibrotic interstitial lung abnormalities in older patients with interstitial lung abnormalities. These findings may assist non-radiological physicians in referring patients to specialists for early intervention in progressive fibrotic interstitial lung diseases., Trial Registration Number/date: UMIN000045149/2021.12.1., Competing Interests: Declarations. Ethics approval and consent to participate: This study complied with the Helsinki Declaration and the protocol, and the informed consent forms were approved by the Institutional Review Boards of Kumamoto University Hospital (approval number: 2368), Saiseikai Kumamoto Hospital (approval number: 809), and Kumamoto Red Cross Hospital (approval number: 464). Written informed consent was obtained from all participants. Patient recruitment commenced on 20 June 2022. Consent for publication: Consent for publication was obtained from all participants and authors. Competing interests: KI, HI, TJ, and TS received lecture fees from Nippon Boehringer Ingelheim Co. Ltd. Boehringer Ingelheim had no role in the design, analysis, or interpretation of the results in this study. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as it relates to Boehringer Ingelheim substances, as well as intellectual property considerations.KI, KK, YY, KA, HO, KA, NH, KF, TS, JM, MY, and KM declare no conflict of interest., (© 2025. The Author(s).)

Background: The variety of shocks in neonates, if not recognized and treated immediately, is a major cause for fatality. The use of echocardiography may improve assessment and treatment, but its reference values across gestational age (GA) and birth weight (BW) are lacking. To address the information gap, this study aimed at correlating GA and BW of newborns with nonhemodynamic abnormalities, and at evaluating the usefulness of such reference values in neonates with early onset septic (EOS) -shock., Methods: A total of 200 normal newborns were enrolled as controls and subdivided into groups based on GA, BW, days of age, and patent ductus arteriosus (PDA). Echocardiography was used to document inferior vena cava diameter (IVC), inferior vena cava collapsibility index (IVC-CI), and inferior vena cava to abdominal aorta ratio (IVC/AO). In addition, 18 neonates with EOS shock were recruited and evaluated using echocardiography., Results: Among the control newborns, IVC and AO were significantly increased with GA and BW (P < 0.05) but IVC-CI and IVC/AO did not correlate with GA, BW, day of age, and PDA. Compared to the control group, the EOS-shock group had significantly decreased IVC and IVC/AO, and increased IVC-CI (P < 0.05). The cut-off values for indicating EOS-shock were > 34.15% for IVC-CI, < 47.58% for IVCmin/AO, and < 66.11% for IVCmax/AO., Conclusions: The IVC-CI, IVCmin/AO, and IVCmax/AO indices are applicable to all neonates. Although the number of neonates with EOS-shock in our study is small, the cut-off values showed usefulness for diagnosis. Further research is needed to determine the application of the indices in a larger population and among other populations, especially for clinical application in treatment of shock among neonates., Competing Interests: Declarations. Ethics approval and consent to participate: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by Shanghai Children’s Medical Center, school of Medicine, Shanghai Jiao tong University, Shanghai, China (reference number: SCMCIRB-K2023108-1). All participants’ responsible guardians were asked for and gave their written consent after being informed about the nature of the study. Consent for publication: Not applicable. Ethics statement: No animals were involved in this study. Competing interests: There was no conflict of interests for this article., (© 2024. The Author(s).)

Background: When designing removable partial dentures, maximizing the effectiveness of support and bracing is necessary to minimize denture movement. Therefore, it is essential to emphasize the importance of providing patients with appropriate, safe, and secure removable partial dentures and have clinicians rerecognize the concept and importance of support and bracing. This study aimed to present extension-base removable partial dentures through six specific clinical case series and describe the effect of support and bracing action on denture design, which is essential for denture movement minimization., A Case Series Study: Case presentation: The case series highlights the importance of utilizing the contact between the axial surface of the abutment tooth and denture components to provide effective support and bracing action. Furthermore, it emphasizes the need to improve the bracing action by connecting the minor connector and proximal plate with the guiding plane set for multiple teeth (frictional control), control the direction of the denture during the placement/removal (path of insertion), and consider the major connector form to improve the support and bracing actions. Effective support and bracing actions are necessary not only for the retainer but also for the denture components, including the design of the denture base and major connector. Removable partial dentures with "frictional control" and "path of insertion" are expected to reduce denture movement and improve stability., Conclusions: The denture design described in this study is essential in pre- and postgraduate dental education, and the author believes that it will be helpful for dental students, interns, or residents in clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: The patient provided written informed consent, and this case report was approved by Ethics Committee School of Dentistry, Aichi Gakuin University (the committee’s reference number 729). Informed consent for the use of photographic materials in dental education and research papers was obtained from the patient and recorded in the medical records. Consent for publication: All patients in this study provided written informed consent for the use of personal or clinical details along with any identifying images for publication in this study. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The metabolic score for visceral fat (METS-VF) is a recently identified index for evaluating visceral fat, also referred to as abdominal obesity. The skeletal muscle mass index (SMI) serves as a critical measure for assessing muscle mass and sarcopenia. Both obesity and the reduction of muscle mass can significantly affect human health. However, research exploring the relationship between METS-VF and SMI remains limited. This study aims to investigate whether a association exists between these two indices, and if so, to elucidate the nature of their interactions., Methods: We conducted a cross-sectional study using data from the NHANES database, focusing on U.S. adults aged 20 years and older from 2013 to 2018. Controlling for relevant covariables, we primarily investigated the association between METS-VF and SMI values utilizing weighted multivariable linear regression models. Additionally, we assessed the diagnostic efficacy of METS-VF for sarcopenia., Results: A total of 3,594 participants were included in this study for analysis. The final adjusted model from the weighted multivariable linear regression indicated that METS-VF was negatively associated with SMI, with a coefficient of β = -0.13 (95% CI: -0.14, -0.12; P < 0.001). Subgroup analyses further demonstrated that this negative association was consistent across different populations. Notably, the negative association varied significantly between diabetic and nondiabetic population, as well as among populations classified by different BMI categories. Additionally, threshold effect analysis identified a significant inflection knot at 6.33. The characteristic curves of the subjects' work illustrated that, compared to other indicators, METS-VF exhibited excellent diagnostic efficacy for sarcopenia, with an area under the curve (AUC) of 0.825., Conclusion: Our results indicate that METS-VF is negatively correlated with SMI among adults in the United States, suggesting that visceral obesity exerts a detrimental effect on muscle mass. Furthermore, METS-VF shows potential as a valuable indicator for assessing SMI and sarcopenia. These findings underscore the importance of considering lipid metabolism disorders in the context of muscle health and highlight the potential for developing prevention strategies for sarcopenia., Competing Interests: Declarations. Ethics approval and consent to participate: This survey of the United States population was approved by the authorities of the National Center for Health Statistics. and the survey was conducted in accordance with local institutional and regulatory standards. All participants signed an informed consent form. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Immune cells within tumor tissues play important roles in remodeling the tumor microenvironment, thus affecting tumor progression and the therapeutic response. The current study was designed to identify key markers of plasma cells and explore their role in high-grade serous ovarian cancer (HGSOC)., Methods: We utilized single-cell sequencing data from the Gene Expression Omnibus (GEO) database to identify key immune cell types within HGSOC tissues and to extract related markers via the Seurat package. The effects of immune cell markers on prognosis were analyzed via univariate Cox regression, least absolute shrinkage and selection operator (LASSO) and gene set variation analysis (GSVA) of bulk sequencing data from The Cancer Genome Atlas (TCGA)-HGSOC cohort. Finally, the effects of key markers on HGSOC cells were evaluated via Cell Counting Kit-8 (CCK-8), Transwell, colony formation, wound healing, immunofluorescence and in vivo tumor growth assays., Results: At the single-cell level, we detected a significant increase in the proportion of plasma cells in HGSOC samples compared to that in normal ovarian samples. Within HGSOC tissues, these plasma cells were found to interact with CD8 + T cells, fibroblasts and endothelial cells. In addition, patients in the high-plasma cell-related score group had better survival rates and higher epithelial‒mesenchymal transition (EMT), apoptosis and immune scores. Moreover, univariate Cox and LASSO regression analyses revealed that ubiquitin-conjugating enzyme E2 J1 (UBE2J1) is a prognostic marker in HGSOC. Further functional studies revealed that overexpression of UBE2J1 promoted cell proliferation, invasion, migration and colony formation, whereas UBE2J1 knockdown attenuated the abovementioned cellular behaviors. Additionally, UBE2J1 overexpression promoted EMT, as evidenced by alterations in the protein expression levels of N-cadherin, snail family transcriptional repressor 2 (Slug), Twist family BHLH transcription factor 1 (Twist 1) and E-cadherin. Moreover, we found that UBE2J1 silencing was able to inhibit the tumor growth in vivo., Conclusions: Overall, this study elucidated the role of plasma cells and revealed UBE2J1 as a novel oncogene in HGSOC, uncovering new mechanisms related to HGSOC tumorigenesis and promising therapeutic targets for HGSOC patients., Competing Interests: Declarations. Ethics approval and consent to participate: All experiments were conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (Approval no. 2023KS157, Approval date: 29/12/2023). Informed consents were obtained from all individuals involved in the study. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Background: Low family socio-economic status is a known factor that can contribute to increased mortality for patients with cardiovascular disease. However, in developing countries, the prognostic impact of socio-economic level on pediatric HTx is unclear., Methods: We conducted a retrospective cohort analysis of children younger than 18 years who underwent heart transplantation (HTx) at our center from October 1, 2005, to May 31, 2023. To assess the impact of socio-economic status, we followed up with the discharged children until September 30, 2023, monitoring for all-cause mortality and unplanned readmission events. To evaluate the relationship between socio-economic status and prognosis, we assigned a composite score based on an assessment of household income, parental education level, and occupation. The Cox proportional hazards model and the Kaplan-Meier method were utilized for this analysis., Results: 64 children (median age at operation 14 years, IQR 13-15) were enrolled and one case died in hospital due to primary graft dysfunction, 63 (98.4%) children had a median follow-up of 60 months (IQR 5.9-113.9). During the follow-up period, 10 (15.9%) children died, and 20 (31.7%) children had 25 unplanned readmissions. Children had higher all-cause mortality and more unplanned readmissions in families with low socio-economic status (n = 33) than middle (n = 10) or high (n = 20) family socio-economic status. Hazard ratios were 5.99,(95%CI:2.28-10.64, P = 0.003) for all-cause mortality for low versus high family socio-economic status, and 2.53 (95%CI:1.04-9.43, P = 0.029) for middle versus high family socio-economic status., Conclusions: Lower family socio-economic status is associated with a worse prognosis than high family socio-economic status. Measures to alleviate economic disparities are needed to improve the prognosis of pediatric HTx., Competing Interests: Declarations. Ethics approval and consent to participate: The Institutional Review Board (IRB) of the Fuwai hospital according to the declaration of Helsinki approved the study program and the publishing of the data. Ethical Approval number: 2022 − 1727. Informed consent was obtained from all the participants and each child’s parent or guardian. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Previous studies highlighted the association between the triglyceride-glucose (TyG) index and cardiovascular events in patients with diabetes. However, whether diabetes affects TyG-cardiovascular diseases (CVD) is still unclear. This study aimed to evaluate the association between the TyG index and CVD risk, stratified by diabetes status, as well as the potential modifying effect of diabetic status., Methods/design: The PubMed, Cochrane Library, and Embase databases were searched for studies on the associations between the TyG index and cardiovascular events and mortality in patients with and without diabetes from inception to December 2, 2024. The random effects model was employed to pool the effect sizes., Results: A total of 50 cohort studies (7,239,790 participants) were included. The mean age of participants was 31.46 years (diabetes mellitus [DM]: 65.18; non-DM: 31.23), and 40.66% of participants were female (DM: 36.07%; non-DM: 40.70%). The associations between the TyG index and cardiovascular events (HR: 1.72 vs. 1.55, P = 0.55), major adverse cardiovascular and cerebrovascular events (HR: 2.02 vs. 1.91, P = 0.84), stroke (HR: 1.46 vs. 1.39, P = 0.77) and cardiovascular death (HR: 1.85 vs. 1.60, P = 0.56) were similar among DM and non-DM individuals. However, the associations between the TyG index and ischemic heart disease (IHD) (HR: 2.20 vs. 1.57, P = 0.03) as well as all-cause mortality (HR: 1.94 vs. 1.24, P = 0.01) were stronger in DM patients than in non-DM patients., Conclusion: TyG index showed association with cardiovascular events, mortality, and all-cause mortality independent of diabetic status, with low to moderate certainty. The associations for IHD and all-cause death were stronger in diabetic patients than in individuals without diabetes. Future studies should explore the role of diabetes in the TyG index-associated CVD outcomes and mortality., Competing Interests: Declarations. Ethical approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)