OBJECTIVE To investigate the current status of pharmaceutical care in medical institutions in China， and provide experience and suggestions for better development of pharmaceutical care. METHODS Questionnaire survey was used to investigate the development of pharmaceutical care in medical institutions in 31 provinces （autonomous regions and municipalities directly） in March 2023， and descriptive analysis and binary logistic regression analysis on the influencing factors of pharmaceutical care were conducted. RESULTS A total of 1 368 questionnaires were sent out， and 1 304 valid questionnaires were collected with the effective recovery rate of 95.32%. Pharmaceutical care was carried out in 671 medical institutions （51.46%）， and the rates of pharmaceutical care in tertiary， secondary， primary and other medical institutions were 74.79%， 27.97% and 7.35%， respectively. The average number of patients receiving pharmaceutical care was 2 638.96 per year， and there were 8.33 pharmacists in each medical institution to carry out pharmaceutical care， among which 93.68% were clinical pharmacists. The main departments covered by pharmaceutical care services included respiratory and critical care medicine， cardiology， intensive care unit， endocrinology， oncology， gastroenterology， obstetrics and gynecology and other departments. There were only 48 medical institutions （7.15%） with additional compensation for pharmaceutical care services. The main experiences of developing pharmaceutical care were to pay attention to talent cultivation and discipline construction， but the main difficulties were serious shortage of staff and qualified talents， low compensation level and low enthusiasm. Grade of medical institutions， the number of pharmacists engaged in clinical pharmacy， the number of qualified clinical pharmacists and the degree of information in the pharmacy department were the main influencing factors for carrying out pharmaceutical care （P＜0.05）. CONCLUSIONS In recent years， pharmaceutical care in Chinese medical institutions has made certain progress， while that of primary medical institutions， secondary medical institutions and other medical institutions should be improved. In the future， it is still necessary to further enhance the implementation of pharmaceutical care， promote personnel training， and attach importance to demonstrating the value of pharmaceutical care， thereby promoting the sustainable and high- quality development of pharmaceutical care.

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Kirsten rat sarcoma viral oncogene homolog (KRAS) protein inhibitors are a promising class of therapeutics, but research on molecules that effectively penetrate the blood-brain barrier (BBB) remains limited, which is crucial for treating central nervous system (CNS) malignancies. Although molecular generation models have recently advanced drug discovery, they often overlook the complexity of biological and chemical factors, leaving room for improvement. In this study, we present a structure-constrained molecular generation workflow designed to optimize lead compounds for both drug efficacy and drug absorption properties. Our approach utilizes a variational autoencoder (VAE) generative model integrated with reinforcement learning for multi-objective optimization. This method specifically aims to enhance BBB permeability (BBBp) while maintaining high-affinity substructures of KRAS inhibitors. To support this, we incorporate a specialized KRAS BBB predictor based on active learning and an affinity predictor employing comparative learning models. Additionally, we introduce two novel metrics, the knowledge-integrated reproduction score (KIRS) and the composite diversity score (CDS), to assess structural performance and biological relevance. Retrospective validation with KRAS inhibitors, AMG510 and MRTX849, demonstrates the framework's effectiveness in optimizing BBBp and highlights its potential for real-world drug development applications. This study provides a robust framework for accelerating the structural enhancement of lead compounds, advancing the drug development process across diverse targets.

Foot-and-mouth disease (FMD) is one of the major animal infectious diseases in the world. All cloven-hoofed animals are susceptible to FMD. Vaccination is still the first choice for the prevention and control of FMD. mRNA vaccines can be rapidly designed, synthesized, and produced on a large scale in vitro, and they can induce effective protective immune responses, demonstrating the advantages of rapid development, easy preparation, and low biosafety risks. The design of untranslated regions is a key to enhancing the expression and efficacy of mRNA vaccines. In order to generate an efficient FMD mRNA vaccine, we designed three FMD P12A3C expression vectors with different untranslated regions and synthesized corresponding mRNAs. By comparing expression efficiency of these vectors and their mRNAs at different time points and in different cell lines, we found that the mRNA P12A3C-UTR3 had the best expression and universality. This study laid a foundation for the development of mRNA vaccines against FMD and provided a theoretical basis for the optimal sequence design of efficient mRNA.
Foot-and-Mouth Disease Virus/genetics* ; Animals ; RNA, Messenger/biosynthesis* ; Foot-and-Mouth Disease/immunology* ; Antigens, Viral/biosynthesis* ; Viral Vaccines/biosynthesis* ; Genetic Vectors/genetics* ; Cell Line ; Vaccines, DNA/immunology*

Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.

Humans are born under the nourishment of heaven and earth qi.The physiological and pathological functions of the human body are influenced by the alternation of cold and heat in the four seasons.Allergic diseases often occur or worsen during seasonal transitions,corresponding to the theory of the spleen dominating the end of the four seasons in traditional Chinese medicine.Splenic dysfunction disrupts the body's internal clock during seasonal transitions,making it unable to adapt to external climate changes,causing the onset or exacerbation of specific allergic symptoms.The theory of"the spleen serves as the guard"originated from Huangdi Neijing,which is a succinct summary of the role of the spleen in defending the body against external pathogens.The theory emphasizes that the spleen transports drinks and foods internally to supplement healthy qi,and regulates defensive qi externally to protect the whole body.This theory is closely linked to the seasonal changes in immune function,thereby influencing the seasonal onset of allergic diseases.This paper explores the roles of the spleen in time-based self-regulation and immune defense against seasonal allergic diseases according to the theory of"spleen serves as the grard."The dysfunction of this protective mechanism,which leads to disharmony in nutritive qi and defensive qi,internal production of phlegm-dampness,and zang-fu organs malnutrition,are the key factors causing recurrent and persistent allergic diseases during seasonal transitions.This study provides insights for elucidating the mechanisms behind seasonal allergic disease outbreaks and their prevention.