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.

This study aimed to construct an evidence map and conduct a comprehensive analysis of clinical research literature on the treatment of pulmonary fibrosis with proprietary Chinese medicines published over the past three decades, so as to systematically evaluate the effectiveness and limitations of existing evidence and provide a scientific basis for subsequent clinical practice, research directions, and policy-making. A systematic search was conducted across 7 databases in both Chinese and English from the inception of the databases to June 1, 2024. The clinical research characteristics and methodological quality of the included literature were assessed. A total of 123 pieces of literature were ultimately included, comprising 108 interventional studies, 3 observational studies, 10 secondary study, and 2 expert consensuses. These studies involved 33 kinds of proprietary Chinese medicines, with Danhong Injection being the most widely used. Most studies had a duration of 1-3 months and a sample size ranging from 50 to 100 cases, and they were often used in combination with steroids or conventional western medicine. There was a common phenomenon of off-label use of proprietary Chinese medicines. The main outcome indicators included pulmonary function, blood gas analysis, and total effective rate, with issues such as insufficient safety reporting, lack of distinctive traditional Chinese medicine(TCM) features, absence of long-term outcome indicators, and strong subjective evaluation. In terms of methodological quality assessment, randomized controlled trial(RCT) had biases in randomization and outcome indicator measurement and a risk of selective reporting. Meta-analysis lacked reporting on protocol registration, literature exclusion lists, and disclosure of conflicts of interest. Expert consensuses lacked standards in terms of rigor, scientific basis, and applicability. The quality of clinical research evidence on the treatment of pulmonary fibrosis with proprietary Chinese medicines urgently needs improvement. It is recommended that future research should pay more attention to the scientific and rigorous design to enhance the standardization and reproducibility of the research. At the same time, it should integrate TCM theories to establish an outcome indicator evaluation system suitable for the treatment of pulmonary fibrosis with proprietary Chinese medicines, so as to fully explore the potential of proprietary Chinese medicines in treating pulmonary fibrosis.
Drugs, Chinese Herbal/administration & dosage* ; Humans ; Pulmonary Fibrosis/drug therapy* ; Medicine, Chinese Traditional

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*

Intentional tooth replantation (ITR) is an advanced treatment modality and the procedure of last resort for preserving teeth with inaccessible endodontic or resorptive lesions. ITR is defined as the deliberate extraction of a tooth; evaluation of the root surface, endodontic manipulation, and repair; and placement of the tooth back into its original socket. Case reports, case series, cohort studies, and randomized controlled trials have demonstrated the efficacy of ITR in the retention of natural teeth that are untreatable or difficult to manage with root canal treatment or endodontic microsurgery. However, variations in clinical protocols for ITR exist due to the empirical nature of the original protocols and rapid advancements in the field of oral biology and dental materials. This heterogeneity in protocols may cause confusion among dental practitioners; therefore, guidelines and considerations for ITR should be explicated. This expert consensus discusses the biological foundation of ITR, the available clinical protocols and current status of ITR in treating teeth with refractory apical periodontitis or anatomical aberration, and the main complications of this treatment, aiming to refine the clinical management of ITR in accordance with the progress of basic research and clinical studies; the findings suggest that ITR may become a more consistent evidence-based option in dental treatment.
Humans ; Tooth Replantation/methods* ; Consensus ; Periapical Periodontitis/surgery*

OBJECTIVE: To observe the effects of enhanced rehabilitation on the prognosis of critically ill patients in the intensive care unit (ICU). METHODS: A single-center retrospective historical controlled study was conducted, patients admitted to the ICU of Peking University First Hospital from May 1, 2020, to April 30, 2021, and from October 1, 2021, to September 30, 2022 were enrolled. According to the different rehabilitation treatment strategies during different periods, patients were divided into the conventional rehabilitation group (patients receiving conventional rehabilitation treatment from May 1, 2020, to April 30, 2021) and the enhanced rehabilitation group (patients receiving the therapy of multidisciplinary team, ie medical care-rehabilitation-nursing care from October 1, 2021, to September 30, 2022). General data, acute physiology and chronic health evaluation II (APACHE II), and study endpoints were collected. Primary endpoints included rehabilitation-therapy rate, intervention time for rehabilitation, rehabilitation-related adverse events, and prognostic indicators such as (length of stay in hospital, length of stay in the ICU, and duration of mechanical ventilation). Secondary endpoints included incidence of deep vein thrombosis and hospital mortality. Kaplan-Meier curves were used to analyze cumulative discharge rates within 50 days. RESULTS: A total of 539 ICU patients were enrolled, with 245 in the conventional rehabilitation group and 294 in the enhanced rehabilitation group; 322 patients had an APACHE II score ≤ 15, while 217 patients had an APACHE II score > 15. Compared to the conventional rehabilitation group, the enhanced rehabilitation group demonstrated significantly higher rehabilitation-therapy rate [51.70% (152/294) vs. 11.43% (28/245)], earlier intervention time for rehabilitation [days: 2.00 (1.00, 3.00) vs. 4.00 (3.00, 7.00)]; shorter length of stay in hospital [days: 18.00 (12.00, 30.00) vs. 21.00 (13.00, 36.00)] and lower incidence of DVT [17.01% (50/294) vs. 24.08% (59/245)]. The differences were all statistically significant (all P < 0.05). There were no rehabilitation-related adverse events occurred in either group. Kaplan-Meier analysis demonstrated a significantly higher cumulative discharge rate within 50 days in the enhanced rehabilitation group compared to the conventional rehabilitation group [86.7% (255/294) vs. 82.9% (203/245); Log-Rank test: χ² = 4.262, P = 0.039]. Subgroup analysis showed that for patients with APACHE II score ≤ 15, the enhanced rehabilitation subgroup had higher rehabilitation-therapy rate [44.32% (78/176) vs. 6.16% (9/146), P < 0.05]. For patients with APACHE II score > 15, compared to the conventional rehabilitation group, the enhanced subgroup demonstrated higher rehabilitation-therapy rate [62.71% (74/118) vs. 19.19% (19/99), P < 0.05] and shorter length of stay in hospital [days: 20.50 (12.00, 31.25) vs. 26.00 (16.00, 43.00), P < 0.05]. CONCLUSIONS Enhanced rehabilitation therapy with medical care, rehabilitation and nursing care, improved rehabilitation-therapy rate, advanced time of rehabilitation treatment, reduced length of stay in hospital and incidence of deep vein thrombosis in critically ill patients, particularly benefited those with APACHE II score > 15. The enhanced rehabilitation was beneficial to the patient in the intensive care unit with safety and worth more investigation.
Humans ; Retrospective Studies ; Critical Illness/rehabilitation* ; Intensive Care Units ; Prognosis ; Length of Stay ; APACHE ; Historically Controlled Study ; Male ; Female ; Middle Aged ; Aged

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.