Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Spermatogenesis is a highly ordered and spatiotemporally regulated developmental process in the male reproductive system, during which spermatogonial stem cells (SSCs), supported by the seminiferous tubule microenvironment, sequentially undergo mitosis, meiosis, and spermiogenesis to ultimately generate structurally intact spermatozoa. This complex process is accompanied by extensive transcriptional reprogramming, chromatin remodeling, and finely tuned post-transcriptional regulation. Precise control of RNA fate is therefore essential for maintaining the continuity and fidelity of spermatogenesis, and its disruption represents a major molecular basis of male infertility. N⁶-methyladenosine (m⁶A), the most abundant internal RNA modification in eukaryotes, has emerged as a critical regulator of post-transcriptional gene expression. m⁶A methyltransferases (“writers”) catalyze the addition of a methyl group to the N⁶ position of adenosine, m⁶A demethylases (“erasers”) remove the modification, and m⁶A-binding proteins (“readers”) recognize m⁶A-modified transcripts. Through the coordinated actions of these factors, m⁶A regulates transcript fate at multiple levels, including RNA splicing, nuclear export, stability, translation, and decay. Emerging evidence indicates that m⁶A-mediated regulation is essential across multiple stages of spermatogenesis, including SSC self-renewal and differentiation, meiotic progression, maintenance of chromosomal stability, and sperm morphogenesis. Beyond its intrinsic functions in germ cells, m⁶A also contributes to the regulation of the testicular microenvironment. In sertoli cells, m⁶A is involved in maintaining blood-testis barrier integrity, RNA processing, and paracrine signaling, thereby providing structural and metabolic support for germ cell development. In Leydig cells, m⁶A regulates steroidogenesis, particularly testosterone synthesis, and participates in cellular stress responses and metabolic homeostasis. Through these mechanisms, m⁶A indirectly influences spermatogenesis by modulating the functional state of testicular somatic cells, highlighting an integrated regulatory mode that combines cell-intrinsic and microenvironment-mediated effects. Notably, distinct classes of m⁶A regulators exhibit pronounced stage-specific functions and coordinated division of labor, collectively forming a multilayered and dynamic regulatory network. Writers often display dosage- and temporal window-dependent effects; erasers contribute to stage-specific demethylation and functional compensation; while readers function through a “switch-buffer” dual-layer architecture, and RNA-binding proteins (RBPs) participate in substrate selection and post-transcriptional regulation. Importantly, emerging evidence suggests that some m⁶A-related proteins can function through noncanonical mechanisms independent of m⁶A recognition, such as intrinsic RNA-binding activity, helicase function, or ribonucleoprotein complex assembly, thereby expanding the functional landscape of the m⁶A regulatory system. Dysregulation of m⁶A machinery can lead to multiple spermatogenic defects, including impaired SSC self-renewal, meiotic arrest, abnormal chromatin remodeling, and defective sperm formation, ultimately resulting in male infertility. Despite substantial advances, several critical questions remain unresolved, including the distinction between m⁶A-dependent and -independent mechanisms, the spatiotemporal dynamics of m⁶A modifications at single-cell resolution, and the coordination and antagonism among different regulatory factors. In this review, we systematically summarize the dual regulation of spermatogenesis by germ cell-intrinsic mechanisms and the testicular microenvironment, and delineate the molecular mechanisms and stage-specific functions of the dynamic m⁶A regulatory network. We further discuss the current limitations in the field and propose feasible experimental strategies for future investigation. Collectively, this work aims to provide a comprehensive framework for understanding the epitranscriptomic regulation of spermatogenesis and to offer theoretical insights into the pathogenesis and clinical management of male infertility.

Objective:To analyze the research trends and hotspots of bupivacaine liposomes from 1994 to 2023 using bibliometrics.Methods:A comprehensive search was conducted for the literature related to bupivacaine liposomes in the Web of Science Core Collection from 1994 to 2023. The CiteSpace software was used to conduct an in-depth analysis of the included literature data, including publication year, country, institution, author, journal, cited references, keywords, etc.Results:A total of 875 papers related to bupivacaine liposomes were included. The research and development of bupivacaine liposomes were divided into 3 stages: slow development (1994-2011), a sharp rise (2011-2021), and stabilization (2021-2023). The United States was in a leading position in terms of the number of publications, centrality, and author cooperation, and Harvard University had the largest number of publications. de Paula E had the most publications, Bramlett K had the highest number of citations, and Boogaerts J had the highest centrality of publications. Journals such as Anesthesia and Analgesia made significant contributions to this field. The most cited references focused on the infiltration of wounds and the periprosthetic injection of bupivacaine liposomes. The keyword analysis showed that local anesthetics, postoperative pain, etc. were commonly used keywords, and enhanced recovery after surgery was an emerging hotspot. Conclusions:Bupivacaine liposomes show good application prospects in the field of peripheral nerve block due to their unique pharmacological properties and safety characteristics and are expected to prolong the duration of postoperative analgesia. However, there is a difference between the actual effect and the expectation, and more clinical trials are needed to evaluate the curative effect, providing a more solid and reliable theoretical basis and practical guidance for clinical practice.

Background and Aims:Laparoscopic pancreaticoduodenectomy(LPD)has become a preferred approach for periampullary tumors,yet delayed gastric emptying(DGE)remains a frequent complication that hampers postoperative recovery.The nasojejunal feeding tube(NJT)is commonly used for early enteral nutrition,but its impact on DGE is controversial.This study aimed to evaluate whether intraoperative NJT placement increases the risk of DGE after LPD and to assess its influence on postoperative recovery outcomes.Methods:A retrospective cohort of 319 patients who underwent LPD at Provincial Hospital Affiliated to Shandong First Medical University from April 2017 to November 2023 was analyzed.Patients were divided into two groups based on intraoperative NJT placement(NJT group,n=200;non-NJT group,n=119).The incidence of DGE and postoperative outcomes were compared.Multivariate logistic regression and propensity score matching(PSM)were performed to identify independent risk factors for DGE.Results:The incidence of grade B/C DGE was significantly higher in the NJT group than in the non-NJT group(36.5%vs.21.8%,P=0.006).NJT placement was associated with longer postoperative hospital stay and higher hospitalization costs(both P<0.05).Multivariate analysis revealed intraoperative NJT placement(OR=1.960,95%CI=1.142-3.363,P=0.015)and intraoperative blood loss>400 mL(OR=1.921,95%CI=1.155-3.194,P=0.012)as independent risk factors for DGE.These findings were consistent after PSM.Conclusions:Prophylactic intraoperative NJT placement confers no additional benefit for postoperative recovery after LPD and is associated with a higher risk of DGE,prolonged hospitalization,and increased medical costs.Routine NJT placement should therefore be avoided,and individualized strategies should be adopted to minimize postoperative complications and enhance recovery.

Head and neck squamous cell carcinoma(HNSCC)is the sixth most common malignant tumor in the world.Due to its high incidence,poor prognosis,relapse-prone characteristics,and the existence of treatment resist-ance,HNSCC has a serious impact on patients'daily lives.As a bridge between innate immunity and adaptive immu-nity,dendritic cell(DC)plays a crucial role in tumor progression.In recent years,numerous studies have found that DC has complex and diverse functions in the tumor microenvironment(TME),and has a significant impact on the oc-currence and development of HNSCC.In this article,we provide a review of the mechanism of DC in HNSCC TME.

Robot-assisted surgery with its advantages such as three-dimensional high-definition vision, dexterous robotic arms, and tremor filtration, is increasingly being applied to complex radical gastrectomy. However, the role of the surgical assistant remains crucial during the procedure. The assistant is responsible for tasks outside the console, including adjusting robotic arms, changing instruments, exposing the surgical field, and addressing unexpected situations. The technical proficiency of the assistant and their collaboration efficiency with the primary surgeon directly impact the smoothness of surgery and patients' outcomes. With the expansion of robot-assisted surgical indications, the establishment of a standardized training system and the optimization of team collaboration models have become urgent challenges to address. This article draws on the author's practical experience as an assistant in robot-assisted gastric cancer surgeries, conducting an in-depth analysis of the responsibilities and operational skills of surgical assistants in robot-assisted procedures. The aim is to develop a relatively comprehensive set of operational guidelines for surgical assistants in robot-assisted radical gastrectomy, providing valuable references for enhancing the overall efficiency of surgical teams and improving surgical outcomes.

Objective:To analyze the research trends and hotspots of bupivacaine liposomes from 1994 to 2023 using bibliometrics.Methods:A comprehensive search was conducted for the literature related to bupivacaine liposomes in the Web of Science Core Collection from 1994 to 2023. The CiteSpace software was used to conduct an in-depth analysis of the included literature data, including publication year, country, institution, author, journal, cited references, keywords, etc.Results:A total of 875 papers related to bupivacaine liposomes were included. The research and development of bupivacaine liposomes were divided into 3 stages: slow development (1994-2011), a sharp rise (2011-2021), and stabilization (2021-2023). The United States was in a leading position in terms of the number of publications, centrality, and author cooperation, and Harvard University had the largest number of publications. de Paula E had the most publications, Bramlett K had the highest number of citations, and Boogaerts J had the highest centrality of publications. Journals such as Anesthesia and Analgesia made significant contributions to this field. The most cited references focused on the infiltration of wounds and the periprosthetic injection of bupivacaine liposomes. The keyword analysis showed that local anesthetics, postoperative pain, etc. were commonly used keywords, and enhanced recovery after surgery was an emerging hotspot. Conclusions:Bupivacaine liposomes show good application prospects in the field of peripheral nerve block due to their unique pharmacological properties and safety characteristics and are expected to prolong the duration of postoperative analgesia. However, there is a difference between the actual effect and the expectation, and more clinical trials are needed to evaluate the curative effect, providing a more solid and reliable theoretical basis and practical guidance for clinical practice.

Objective:To explore the predictive value of very low frequency (VLF) for the efficacy of vitamin D treatment in children with postural orthostatic tachycardia syndrome (POTS).Methods:A retrospective case-control study was conducted. A total of 65 POTS children from the Department of Pediatrics of the Second Hospital of Lanzhou University from November 2023 to May 2024 were selected as the research subjects, while 102 healthy children from the same period were selected as the control group. The 25 (OH) D levels between POTS children and healthy children were compared. The frequency of eight main symptoms, including palpitations, headache, cold sweat, blurred vision, chest tightness, dizziness, fainting, and digestive discomfort in the POTS group were analyzed, the symptom scores of the orthostatic intolerance were calculated, and the parameters related to short-range heart rate variability (HRV) during the upright test, head-up tilt test (HUTT) were collected. The correlation between 25 (OH) D levels and symptom scores of orthostatic intolerance symptoms and HRV parameters in children with POTS were analyzed by Pearson correlation analysis. The total symptom scores of children with POTS were compared for 3 months before treatment and 2 months after treatment with vitamin D 800 U/d. The difference in score before and after treatment was ≥2 as responsive group, and the score difference before and after treatment was <2 as non-responsive group. The demographic characteristics including age, gender, height, weight, body mass index, as well as HRV parameters such as the standard deviation of nn intervals (SDNN), the standard deviation of the average NN intervals (SDANN), the root mean square of successive differences (rMSSD), low-frequency (LF), high-frequency (HF), very-low-frequency (VLF) were compared between the responsive group and non-responsive group. Multivariate Logistic regression was analyzed to screen independent influencing factors of vitamin D treatment efficacy for POTS. The marker molecules related to the efficacy of vitamin D treatment in children with POTS were analyzed through receiver operating characteristic (ROC) curve.Results:A total of 167 children were included in this study. There were 65 children in the POTS group, 38 males and 27 females, with the age of (10.6±2.2) years. There were 102 healthy children in the control group, 53 males and 49 females, with the age of (11.2±1.8) years.There was no statistically significant difference in gender and age between the two groups (both P>0.05). The serum 25 (OH) D level in children in the POTS group was (37±18)nmol/L, lower than that in the control group (61±17)nmol/L ( P<0.05).Pearson correlation analysis showed that serum 25(OH)D was positively correlated with VLF, SDNN and HF ( r=0.43, 0.65, 0.36, respectively, all P<0.05). Among the POTS children, there were 48 cases in responsive group and 17 cases in non-responsive group. Univariate analysis revealed that responsive group exhibited significantly lower values in age, SDNN, SDANN, and VLF compared to the non-responsive group (all P<0.05). Multivariate Logistic regression analysis showed that age ( OR=1.47, 95% CI 1.08-2.01), SDNN ( OR=1.01, 95% CI 1.00-1.22) and VLF ( OR=1.01, 95% CI 1.00-1.15) were independent influencing factors in the effect of vitamin D in POTS children (all P<0.05). ROC curve analysis showed that the area under the curve of VLF predicting response to vitamin D treatment for POTS was 0.72 (95% CI 0.58-0.85, P=0.008). When the cutoff value was 1 272 ms 2, the sensitivity and specificity were both 70%. Conclusion:VLF may help predict the efficacy of vitamin D treatment in children with POTS.

Objective:To construct a frailty risk prediction model for elderly patients with CHD based on machine learning, to address the limitations of existing tools and provide evidence-based support for clinical practice.Methods:A retrospective study was conducted on elderly CHD patients hospitalized at the Heart Center of the First Affiliated Hospital of Henan University of Chinese Medicine from September 2023 to March 2024. Meta-analysis and expert meetings were used to identify the risk factors for frailty in elderly CHD patients. Three machine learning algorithms, Logistic Regression, Random Forest, and Support Vector Machine, were used to construct predictive models using R 4.3.1 software. The predictive performance of the models was evaluated using sensitivity, specificity, accuracy, and the area under the receiver operating characteristic curve (AUC).Results:A total of 490 elderly CHD patients were included, with 267 males and 223 females, and an age of (71.02 ± 7.73) years. Among them, 160 patients (32.7%) developed frailty. Of the constructed models, the Random Forest model demonstrated the best predictive performance, with an accuracy of 0.703, recall of 0.629, and F1 score of 0.741, while the AUC was 0.811 (95% CI 0.762-0.850). Conclusions:The Random Forest model exhibited good predictive performance in assessing frailty risk in elderly CHD patients, with high accuracy and reliability. Future external validation studies can further assess its applicability and stability in different populations.