Objective To investigate the causal relationship between immune cells and various molecular subtypes of breast cancer (BC) by using two-sample Mendelian randomization (MR). Methods This study employed a two-sample MR analysis, with 731 immune cell types from the GWAS catalog as the exposure factors and four BC molecular subtypes (HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−) from the BCAC Consortium as the outcome variables. For causal inference, inverse variance weighting (IVW) was employed as the primary analytical method, alongside multiple consistency validation approaches, including MR-Egger, weighted median, weighted mode, simple mode, and Bayesian weighted Mendelian randomization. Reverse MR and sensitivity analyses were employed to effectively evaluate and exclude potential biases and interference from reverse causality. Results Significant causal associations were identified for specific immune cell phenotypes across subtypes. In HR+ BC, the HER2+ subtype was associated with seven immunophenotypes (five protective and two risk increasing), whereas the HER2− subtype was associated with eight immunophenotypes (four protective and four risk increasing). In HR− BC, the HER2+ subtype was associated with five immunophenotypes (one protective and four risk increasing), and the HER2− subtype (triple-negative BC) was associated with seven immunophenotypes (six protective and one risk-increasing). CD28+CD45RA−CD8+ T cells and naive CD8+ T cells have a bidirectional causal relationship with HR+/HER2+ breast cancer, Whereas the expression of CD8 on CD39+CD8+ cells also has a bidirectional relationship with HR+/HER2− breast cancer. Furthermore, CD4−CD8− NKT cells exhibited opposing effect directions in HER2+ versus HER2− subtypes. Conclusion From a genetic perspective, this study confirms the existence of subtype-specific causal associations between immune cell phenotypes and distinct molecular subtypes of BC, revealing heterogeneity in immune regulation.

Heatstroke, a life-threatening illness, poses a significant risk to human health, particularly in high-temperature and high-humidity environments. Timely and effective on-site management is critical for improving patient survival and prognosis. Rapid recognition, rapid assessment, and rapid cooling are the cornerstones of pre-hospital care. However, the absence of a standardized protocol for pre-hospital management of heatstroke has impeded the efficacy of treatment. This consensus, initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army, signifies a collaborative endeavor involving emergency medical personnel, nurses, and administrators from pre-hospital care, emergency departments, and intensive care units in both military and civilian domains. By systematically reviewing evidence-based medicine and clinical expertise in heatstroke prevention, on-site and in-transit care, as well as early treatment in emergency settings, the group has formulated the Expert consensus on pre-hospital emergency management of heatstroke (2024) after extensive discussions and iterative recommendations, which serve as a scientific and standardized framework for pre-hospital heatstroke emergency care. The consensus underscores the pivotal role of enhancing public awareness regarding heatstroke prevention and augmenting the rates of rapid recognition and rapid cooling for effective on-site heatstroke management. In high-risk industries, regions, or seasons for heatstroke, developing scientifically sound plans and conducting practical training can provide effective safety measures. Emergency personnel should undergo specialized training and assessments in knowledge and skills, ambulances should be equipped with effective cooling devices, and hospitals must maintain comprehensive emergency response capabilities. It is recommended to establish a regional heatstroke treatment network to optimize the allocation of emergency resources and streamline processes, thereby improving treatment outcomes and response times.
Heat Stroke/prevention & control* ; Humans ; Emergency Medical Services ; Consensus

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Proanthocyanidin B_2(PAC-B_2), a polyphenolic dimeric compound comprising two epicatechin molecules linked by a C-C bond, is extensively found in traditional Chinese medicines, with anti-tumor and anti-oxidant activities. Given the limited bioavailability, a thorough investigation and comprehensive understanding of PAC-B_2 metabolism in vivo are essential for elucidating therapeutic forms and mechanisms. In the present study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) in the negative ion mode was employed to acquire the MS/MS information of PAC-B_2 and metabolites in urine and feces samples of the rats administrated with PAC-B_2. Online energy-resolved MS(ER-MS) was applied as supplementary to obtain the full collision energy ramp-MS~2 spectra(FCER-MS~2) of isomers-of-interest, which implied comprehensive MS~2 information of targeted compounds. Finally, the possible metabolic pathways of PAC-B_2 in rats were proposed. The primary fragmentation behaviors of PAC-B_2 in the negative ion mode included quinone methide fission between C_4-C_8 bond, retro Diels-Alder cracking of F-ring, heterocyclic ring fission of C-ring, and neutral loss of small molecules such as H_2O. A total of 25 metabolites were tentatively elucidated in urine and feces samples of rats administrated with PAC-B_2 by fragmentation pattern and reported literature. Two groups of isomers, M3/M4/M5 and M9/M11, were confirmatively differentiated based on the relationships between optimal collision energy provided by FCER-MS~2 and bond properties, including bond length and bond dissociation energy. In addition to the ring-opening and methylation, PAC-B_2 could also be metabolized into epicatechin and low molecular weight phenolic acids, which were subsequently subjected to dehydroxylation, ring-opening, methylation, sulfation, and glucuronidation. The structural information provided by online ER-MS and FCER-MS~2 enabled the differentiation of isomers and improved the identification confidence. More importantly, the present study deeply analyzes the in vivo metabolic pathways of PAC-B_2, providing a basis for the research on the pharmacological mechanism of this compound.
Animals ; Proanthocyanidins/urine* ; Rats ; Male ; Drugs, Chinese Herbal/chemistry* ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Feces/chemistry* ; Molecular Structure

In situ bioimaging is a powerful tool for directly observing the localization, expression, and interactions of nucleic acids or protein targets within cells, providing essential insights into cell function and disease mechanisms. In recent years, the CRISPR/Cas9 system, a revolutionary gene-editing tool, has been applied to develop efficient in situ imaging techniques. This paper reviews recent CRISPR/Cas9-based imaging methods utilizing Cas9 protein, engineered single-guide RNA (sgRNA), and coupled fluorescent tags, and compares their application in living and fixed cells. It focuses on the specificity, signal amplification efficiency, and multi-modal imaging capabilities of these methods, with further discussion based on current research, aiming to offer a comprehensive overview of CRISPR/Cas9-based in situ bioimaging techniques, with some valuable reference and guidance for research in related fields.

Objective: There were associations between emotional abuse and neglect (EAN) and depression, but few studies had tested potential mechanisms underlying these relationships. We aimed to provide insights on how (the mediation role of neuroticism), and under what conditions (the moderator role of psychological resilience), led to a higher level of depression. Methods: This study was a cross-sectional study that used a random cluster sampling method. We randomly selected 3,993 participants from four junior middle schools in northern city of China. Participants were asked to complete four self-reported questionnaires, including the Childhood Trauma Questionnaire, Children Depression Inventory-Short Form, Chinese Big Five Personality Inventory Brief Version, and Chinese Resilience Scale. Results: The results showed that neuroticism mediated the associations between EAN and depression. In addition, the mediating effect of neuroticism was moderated by psychological resilience (p<0.05). Conclusion EAN and neuroticism could have an adverse impact on depression, and psychological resilience could alleviate these negative effects as a moderator. Our model suggested psychological resilience could be a particularly effective intervention point for victims of EAN.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.