ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， the combination of serum pharmacochemistry， response profile of absorbed components in serum， network pharmacology and drug-likeness prediction was used to screen the potential active ingredients of Yanghetang against breast cancer. MethodsUPLC-Q-TOF-MS/MS was used to identify the main components in different solvent extracts of Yanghetang， and serum pharmacochemistry was applied to analyze the absorbed components from the serum of female SD rats after 0.5， 1， 2 h of administration. Combined with the response characteristic values of serum drug components obtained from UNIFI 1.8.2， the absorbed prototype components and metabolites were screened to get the absorbed components of Yanghetang with a significant patterns of elimination and growth. Network pharmacology was applied to construct a drug-component-pathway-target-disease network， and molecular docking was performed between absorbed components and key targets of breast cancer， and the drug similarity was analyzed by SwissADME. ResultsForty-two compounds were identified in Yanghetang samples extracted with different solvents， of which 16 compounds were common to the three different extraction solvents（methanol， 50% methanol and water）. The results of drug-containing serum analysis showed that there were 16 absorbed components in serum， including 5 prototypes and 11 metabolites. Network pharmacology results showed that Yanghetang against breast cancer involved 15 key targets such as proto-oncogene tyrosine-protein kinase Src（SRC）， epidermal growth factor receptor（EGFR） and phosphoinositide 3 kinase catalytic alpha polypeptide（PIK3CA）. Molecular docking results showed that 16 potential active ingredients were well combined with the predicted targets. Combined with drug likenesses， 12 compounds in the absorbed components of Yanghetang were considered to have potential for anti-breast cancer activity， mainly including α-pinene and γ-eudesmol and their metabolites， of which one was from Ephedrae Herba， one was from Rehmanniae Radix， and eight were from Cinnamomi Cortex. ConclusionThe chemical components of Yanghetang mainly include polysaccharides， monoterpene glycosides and coumarins， and its prototype components mainly undergo oxidation， hydrolysis and acetylation after entering the blood. Its anti-breast cancer mechanism may be related to the regulation of signaling pathways such as the mitogen-activated protein kinase（MAPK） and phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）. The results of this study can lay a foundation for further exploration of Yanghetang in the treatment of breast cancer.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

The intestinal barrier is the primary defense that separates the host from the external environment, possessing several crucial physiological functions, including nutrient digestion, absorption, and protection against potentially harmful dietary antigens and pathogenic microorganisms. Nevertheless, various factors, such as diet, medications, circadian rhythm disturbances, gut microbiota, microbial metabolites, and genetic predisposition, can disrupt the intestinal barrier. Such disruption may lead to bacterial translocation, subsequently triggering enterohepatic and systemic inflammation. Impaired intestinal barrier has been implicated in the pathogenesis of numerous diseases, particularly chronic gut and liver diseases. In this review, we will summarize the fundamental functions of intestinal barrier and discuss clinical correlations between intestinal barrier dysfunction and diseases such as colitis, colorectal cancer, and chronic liver diseases including metabolic dysfunction-associated steatohepatitis, alcohol-associated liver disease, and primary sclerosing cholangitis. Additionally, we will also highlight some potential therapeutic strategies aimed at restoring barrier integrity to improve disease management.

The periodontal ligament (PDL) plays a crucial role in transmitting and dispersing occlusal force, acting as mechanoreceptor for muscle activity during chewing, as well as mediating orthodontic tooth movement. It transforms mechanical stimuli into biological signals, influencing alveolar bone remodeling. Recent research has delved deeper into the biological and mechanical aspects of PDL, emphasizing the importance of understanding its structure and mechanical properties comprehensively. This review focuses on the latest findings concerning both macro- and micro- structural aspects of the PDL, highlighting its mechanical characteristics and factors that influence them. Moreover, it explores the mechanotransduction mechanisms of PDL cells under mechanical forces. Structure-mechanics-mechanotransduction interplay in PDL has been integrated ultimately. By providing an up-to-date overview of our understanding on PDL at various scales, this study lays the foundation for further exploration into PDL-related biomechanics and mechanobiology.
Periodontal Ligament/cytology* ; Humans ; Biomechanical Phenomena ; Mechanotransduction, Cellular/physiology* ; Stress, Mechanical

A case of spinal cord abscess caused by Nocardia cyriacigeorgica is reported. The patient is an elderly man with a history of nephritic syndrome who presented with aggravating lower back pain and then gradually developed urinary retention, weakness and numbness in both lower extremities. Operative intervention was performed, and postoperative pathological findings suggested spinal cord abscess formation. Metagenomic next-generation sequencing of the cerebrospinal fluid identified Nocardia cyriacigeorgica as the causative pathogen. Although appropriate antibiotics were prescribed, the patient died 3 months later.

Objective:To investigate the correlation between age and tongue pressure in healthy individuals using a newly-developed tongue pressure measuring device.Methods:A total of 154 healthy volunteers aged 20 to 97 years, without noticeable swallowing difficulties, were selected and divided into seven age groups: 20-29 years ( n=24), 30-39 years ( n=22), 40-49 years ( n=20), 50-59 years ( n=24), 60-69 years ( n=22), 70-79 years ( n=22), and 80 years or more ( n=20). Their maximum, minimum, average and initial pressures, work done, and coefficients of variation were measured using the newly designed tongue pressure measuring device in its intermittent and continuous measurement modes. The tongue pressures were correlated with age and gender. Results:The pressure data obtained using the new device were completely consistent with those from a manometer ( R=1). In the intermittent measurement mode, the readings showed that the maximum, minimum and average tongue pressures decreased significantly with age. In the continuous measurement mode, the initial tongue pressure, average pressure and work done also decreased significantly with age, while the coefficient of variation generally increased with age. There was a negative correlation between age and average tongue pressure ( R2=0.4). The relationship could be expressed as y=-0.8595x+ 103.3 (where x is age, and y is tongue pressure). However, no significant correlation was found between gender and tongue pressure. Conclusions:Tongue pressure and its stability are negatively correlated with age in healthy individuals without swallowing dysfunction, showing no significant correlation with gender.

Objective:To systematically evaluate the qualitative research on the practical experience of hospice care among medical staff in nursing homes, and to provide a reference basis for the implementation of hospice care services in nursing homes.Methods:The qualitative research on the practical experience of hospice care among medical staff in nursing homes was searched from databases including the Web of Science, PubMed, Cochrane Library, Embase, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang Data and VIP Database. The retrieval period was from the establishment of the database to March 21, 2024. The quality evaluation standards for qualitative research of the Australian Joanna Briggs Institute Evidence-Based Health Care Center were used to evaluate the quality of the literature. The results were integrated by the method of aggregative integration.Results:A total of 15 studies were included, and 47 clear research results were extracted, summarized into 11 categories, and 4 integrated results were obtained: the palliative care work responsibilities of medical staff; the emotional experience of medical staff in practice; coping with negative experience and gaining personal growth;the practical dilemmas faced by nursing homes when implementing hospice care.Conclusions:Nursing homes face multiple obstacles and challenges in the process of providing hospice care services. It is recommended that future research should focus on improving the policy system of hospice care in nursing homes, building a support system for hospice care services, and promoting the development and practice of death literacy among the public, so as to promote the healthy and long-term development of hospice care services in nursing homes.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Gynecological diseases are one of the important factors that threaten women's reproductive health.Endoplasmic reticulum(ER)stress is a stress response induced by the accumulation of unfolded or misfolded proteins in ER cavity when the female body is in a disease state,and the effects of different stress levels on the female reproductive system and the increase in the risk of female disease will vary greatly.Studies have shown that ER stress is closely related to the occurrence and development of gynecological diseases.Based on the relevant research reports at home and abroad in recent years,this paper summarizes the role of ER stress in several common gynecological diseases to provide new research ideas for preventing,diagnosing,and treating gynecological diseases.