ObjectiveThis paper used the AGREE Ⅱ guideline evaluation tool to evaluate the quality of 14 clinical guidelines for acute myocardial infarction，aiming to provide reference for the formulation and improvement of the guidelines. MethodsClinical guidelines and expert consensus related to acute myocardial infarction were searched by web search. The search period ranges from January 1，2019 to November 1，2024 in CNKI，VIP，Wanfang Data，SinoMed，Web of Science，OVID， the International Guidelines Collaboration Network （GIN），the UK National Institute for Health and Clinical Excellence （NICE），Yimaitong， and other platforms. Three researchers independently screened the literature and used AGREE Ⅱ to score the screening results. After ensuring that the researchers have a consistent understanding of each guideline，the quality of the guidelines was evaluated. After that，the ratings were analyzed by layer according to the issuing agency，category，method of formulation，and funding situation and compared longitudinally by rating time. The clinical guidelines and expert consensus were compared in terms of content and evidence. ResultsA total of 14 guidelines and consensus were included. The results of AGREE Ⅱ in the six areas in descending order were scope and purpose （62.82%±10.43%），rigor （62.40%±12.77%），editorial independence （62.11%±22.26%），participants （61.42%±11.65%），clarity of expression （59.98%±9.62%），and application （52.94%±16.90%） . Eleven of the guidelines were at level B， and three were at level A. In the stratified analysis，the score of the guideline formulated by the Chinese Medical Doctor Association was lower. There was little difference between the scores of Chinese/Western and Western medicine guidelines. The average score of the guidelines was higher than the consensus. Funded guidelines and consensus scores were higher. In the longitudinal comparison，the highest number of guidelines were developed in 2020 and 2021，while those developed in 2023 scored the highest. In the differential comparison analysis，the content of the guidelines was more comprehensive， and the evidence level was higher，while the content of the consensus was more novel， and the evidence was less. ConclusionThe AGREE Ⅱ score of the clinical guidelines for acute myocardial infarction is generally moderate，and there is room for improvement in terms of applicability. At the same time，the content quality of expert consensus should be improved，and more efforts should be made to develop and apply Chinese medicine guidelines for complications such as heart failure and microcirculatory obstruction after acute myocardial infarction.

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

Tumors exhibit abnormal glucose metabolism, consuming excessive glucose and excreting lactate, which constructs a tumor microenvironment that facilitates cancer progression and disrupts immunotherapeutic efficacy. Currently, tumor glucose metabolic dysregulation to reshape the immunosuppressive microenvironment and enhance immunotherapy efficacy is emerging as an innovative therapeutic strategy. However, glucose metabolism modulators lack specificity and still face significant challenges in overcoming tumor delivery barriers, microenvironmental complexity, and metabolic heterogeneity, resulting in poor clinical benefit. Nanomedicines, with their ability to selectively target tumors or immune cells, respond to the tumor microenvironment, co-deliver multiple drugs, and facilitate combinatorial therapies, hold significant promise for enhancing immunotherapy through tumor glucose metabolic reprogramming. This review explores the complex interactions between tumor glucose metabolism-specifically metabolite transport, glycolysis processes, and lactate-and the immune microenvironment. We summarize how nanomedicine-mediated reprogramming of tumor glucose metabolism can enhance immunotherapy efficacy and outline the prospects and challenges in this field.

Peptide-drug conjugates (PDCs) have emerged as a promising modality in precision oncology, enabling targeted delivery of cytotoxic payloads while minimizing off-target toxicity. The integration of covalent warheads, such as those based on sulfur(VI) fluoride exchange (SuFEx) chemistry, enhances drug-target residence time and tumor accumulation. However, existing screening methods for covalent peptide (CP) libraries require post-translational warhead conjugation, limiting throughput. Here, we present an integrated mRNA display platform that incorporates covalent warheads during ribosomal synthesis, enabling efficient screening of ultra-diverse covalent macrocyclic peptide libraries (>10¹³ variants). This approach, using site-specific incorporation of N-chloroacetyl-d-phenylalanine and fluorosulfate-l-tyrosine, accelerated the discovery of irreversibly binding (K _i = 3.58 μmol/L) Nectin-4-targeting peptide CP-N1-N₃ via proximity-triggered SuFEx. The peptide was further conjugated to cytotoxic payloads, yielding the covalent PDC CP-N1-MMAE with potent cytotoxicity (IC₅₀ ≈ 43 nmol/L) against MDA-MB-468 cells. This platform establishes a new paradigm for precision covalent drug discovery.

OBJECTIVE: To explore the correlation between chromosome 8 open reading frame 76 (C8orf76) and cyclin-dependent kinase 4 (CDK4) and the potential predictive effect of C8orf76 and CDK4 on the prognosis of colorectal cancer (CRC). METHODS: We constructed a protein-protein interaction network of C8orf76-related genes and analyzed the prognostic signatures of C8orf76 and CDK4. Clinicopathological features of C8orf76 and CDK4 were visualized using a nomogram. RESULTS: C8orf76 and CDK4 levels were positively correlated in two independent human CRC cohorts ( n = 83 and n = 597). A consistent positive correlation was observed between C8orf76 and CDK4 expression in the CRC cell lines. The nomogram included prognostic genes (C8orf76 and CDK4) and pathological N and M stages. The concordance index (C-index) in our cohort was 0.776, which suggests that the ability of the indicators to predict the overall survival of patients with CRC in our cohort was strong. CONCLUSION We found that C8orf76 was positively correlated with CDK4 in both the cohorts as well as in CRC cell lines. Therefore, C8orf76 and CDK4 can be used as potential biomarkers to predict the prognosis of CRC.
Humans ; Colorectal Neoplasms/diagnosis* ; Cyclin-Dependent Kinase 4/metabolism* ; Prognosis ; Male ; Female ; Middle Aged ; Biomarkers, Tumor/genetics* ; Aged ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

ERK1/2 is a key protein that mediates cell signal transduction,and it is involved in regulating biological processes such as chromatin remodeling,nuclear disintegration,proliferation,survival,metabolism,and cell migration and differentiation.Its overactivation is closely related to the occurrence and progression of cancer,and the mechanism is manifested as the overactivation of ERK1/2 by gene mutations of upstream pathway molecules or regulators and the reactivation of ERK1/2 after inhibition against the above targets.ERK1/2 is a potentially valuable target.In this review,the mechanism of post-translational modification and spatial regulation of ERK1/2 and the application status of corresponding small-molecule inhibitors were discussed.The current antitumor strategy of targeting and regulating ERK1/2 was summarized,and the possibility of exploring potential targets was elucidated,thus providing new insights into the developmental research of ERK1/2 as an ideal anticancer target.

This article summarizes Professor Shang Lili's experience in diagnosing and treating recurrent respiratory tract infections(RRTIs)in children based on the theory of"internal deficiency and external injury".Professor Shang believes that children are in the stage of growth and development,with delicate organs and insufficient vital energy,which is called"internal deficiency";external pathogens repeatedly invade the human body,resulting in clinical manifestations of both cold and heat,ultimately damaging the body's qi,blood,essence,and spirit,known as"external injury"."Internal deficiency and external injury"leads to repeated infections of pathogens in children and causes physical and mental distress,affecting their growth and development.The theory of"internal deficien-cy and external injury"emphasizes the influence of internal and external factors on RRTIs in children,reflecting the evolution of patho-genesis and guiding clinical staging treatment.During the acute infection period,the treatment of wind heat syndrome is based on the Xin Liang and Qing San methods,while the treatment of wind cold syndrome is based on the Xin Wen and Kai Bi methods.For the mixed deficiency and excess syndrome,various methods such as attacking,supplementing,harmonizing,and supporting should be used,and treatment should be based on syndrome differentiation,with adjustments made according to the symptoms;during the inter-mittent period of infection,Professor Shang aims to assist the righteous qi,taking into account the upper,middle,and lower Jiao,and adopting treatment principles such as nourishing the lungs,spleen,and kidneys.Professor Shang's experience provides useful ideas and methods for the treatment of RRTIs in children.