Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

OBJECTIVE: In order to enhance the efficacy of anti-breast cancer, paclitaxel nanoparticles (PTX NPs) and polypyrrole nanoparticles (PPy NPs) were combined with photothermal therapy and chemotherapy. At the same time, the two dosage forms of PTX NPs and PTX NPs gel were compared. METHODS: PTX NPs were prepared by self-assembly method, and then the cytotoxicity in vitro was investigated by Methyl thiazolyl tetrazolium (MTT) and other methods, and the efficacy and side effects in vivo were further investigated. RESULTS: The average hydrated diameter, PDI and electric potential of PTX NPs were (210.20 ± 1.57) nm, (0.081 ± 0.003) mV and (15.80 ± 0.35) mV, respectively. MTT results showed that the IC₅₀ value of PTX NPs on 4 T1 cells was 0.490 μg/mL, while that of PTX injection was 1.737 μg/mL. The cell inhibitory effect of PTX NPs was about 3.5 times higher than that of PTX injection. The tumor inhibition rates of PTX NPs and gel were 48.64% and 56.79%, respectively. Together with local photothermal stimulation, the tumor inhibition rate of the PTX NPs reached 91.05%, surpassing that of the gel under the same conditions (48.98%), moreover, the organ index and H&E staining results of PTX NPs showed a decrease in toxicity. CONCLUSION This combination therapy can significantly enhance the effect of anti-breast cancer, and the synergistic effect of chemotherapy and light and heat provides a feasible and effective strategy for the treatment of tumor.

The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

Objective:To explore the relationship between the expression of long chain non coding ribonucleic acid (LncRNA) small nucleolar RNA host gene 1 (LncRNA SNHG1) and microRNA (miR)-143-3p in nasopharyngeal squamous cell carcinoma (HSCC) tissue and clinical pathological features and prognosis.Methods:A prospective selection was made from 97 HSCC patients admitted to the Handan Central Hospital from March 2016 to March 2018. Surgical resection of HSCC tissue and normal mucosa tissue adjacent to cancer were taken, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of LncRNA SNHG1 and miR-143-3p. The patient′s survival status was followed up after leaving the hospital. We compared the differences in the expression of LncRNA SNlHG1 and miR-143-3p in HSCC tissues with different clinical pathological parameters, analyzed the correlation between LncRNA SNHG1 and miR-143-3p expression, and the relationship between LncRNA SNHG1 and miR-143-3p expression and the prognosis of HSCC patients.Results:The expression of LncRNA SNHG1 in HSCC tissue was higher than that in normal mucosa tissue adjacent to cancer ( P<0.05), and the expression of miR-143-3p was lower than that in normal mucosa tissue adjacent to cancer ( P<0.05). The expression of LncRNA SNHG1 in cancer tissues of HSCC patients with tumor node metastasis (TNM) stage Ⅲ, low to medium differentiation, and lymph node metastasis was higher than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05), and the expression of miR-143-3p was lower than that of HSCC patients with TNM stage Ⅰ-Ⅱ, high differentiation, and no lymph node metastasis (all P<0.05). The expression of LncRNA SNHG1 in HSCC tissues is negatively correlated with the expression of miR-143-3p ( r=-0.522, P<0.05). The 5-year cumulative survival rate of HSCC patients with high expression of LncRNA SNHG1 was lower than that of HSCC patients with low expression of LncRNA SNHG1 ( P<0.05), and the 5-year cumulative survival rate of HSCC patients with low expression of miR-143-3p was lower than that of HSCC patients with high expression of miR-143-3p ( P<0.05). Multivariate Cox regression analysis showed that TNM stage Ⅲ and high expression of LncRNA SNHG1 were risk factors for poor prognosis in HSCC patients (all P<0.05), while high expression of miR-143-3p was a protective factor ( P<0.05). Conclusions:The expression of LncRNA SNHG1 is upregulated and miR-143-3p is downregulated in HSCC tissues, with a negative correlation between the two, which is related to the malignant pathological characteristics and poor prognosis of HSCC.

Objective:Care bundles for critically ill patients with early enteral nutrition up to goal was constructed. Its purpose was to improve early enteral nutrition, prognosis and provide reference basis for improving the rate of standard of early enteral nutrition in critically ill patients.Methods:By conducting systematic searching of domestic and foreign Chinese and English databases, related guide websites, relevant documents on early enteral nutrition in critically ill patients up to goal, which were obtained, evaluated, extracted, summarized and graded. After discussion by the research group, the first draft was prepared. Delphi method was used to conduct two rounds of expert correspondence, and the final draft of the proposal was established through the reliability analysis of correspondence results.Results:Twenty experts participated finally, and their opinions tended to be consistent after two rounds of expert inquiry. The authority coefficients were 0.92 and 0.91 respectively. The variation coefficients of the importance and operability of the two rounds of correspondence items were 0.05-0.20 and 0.05-0.21, 0.00-0.17 and 0.00-0.20 respectively. The Kendall concordance coefficients for the importance and operability of the two rounds of correspondence items were 0.16 and 0.13, 0.27 and 0.18 respectively. The differences were statistically significant ( χ2 values were 117.01-228.43, all P<0.05). Finally, the final draft of bundle of care for early enteral nutrition up to goal in critically ill patients was established which included three aspects related to evaluation, implementation, and effectiveness monitoring, besides care bundle included 12 intervention perspectives and 29 specific intervention measures. Conclusions:Based on evidence-based and delphi method constructing care bundles for critically ill patients with early enteral nutrition up to goal was scientific, reliable and practical which could provide theoretical and practical guidance for bundled nursing interventions to meet early enteral nutrition standards in critically ill patients.

Against the backdrop of rapid economic development and ongoing reforms in the healthcare system,the cover-age and quality of medical services in China are steadily improving.However,this progress is also accompanied by new challen-ges,particularly the frequent occurrence of emergencies.Cultural diversity and differences in ideological concepts serve as signifi-cant catalysts,exacerbating the complexity and unpredictability of these incidents.As a cornerstone of the healthcare system,public hospitals face particularly severe challenges in responding to emergencies.Limited by inadequate medical service levels,ethical standards,doctor-patient relationship management,and crisis response capabilities,public hospitals often encounter sub-stantial difficulties in crisis resolution.In light of this,this paper conducts an in-depth analysis of the multidimensional factors contributing to medical crises in hospitals,carefully identifying the key issues in crisis management.It proposes a series of targe-ted and actionable strategies centered around critical aspects such as crisis early warning mechanisms,accurate identification,ef-ficient response,strict control,timely feedback,and comprehensive summarization.The aim is to enhance public hospitals'abili-ty to respond to emergencies through scientific planning and effective implementation,ensuring the stability and sustainable devel-opment of healthcare services.

Objective:To explore the latent profile types of capability-opportunity-motivation-behavior in stroke patients and analyze the influencing factors of different latent profiles.Methods:From January to October 2023, totally 596 stroke patients from the Neurology Department of five ClassⅢ Grade A hospitals in Henan Province were selected by stratified random sampling. The patients were surveyed using a general information questionnaire, the Stroke Prevention Knowledge Questionnaire (SPKQ), the Social Support Rating Scale (SSRS), the WHO's Quality of Life Questionnaire- Brief Version (WHOQOL-BREF), the Short Form Health Belief Model Scale (SF-HBMS), and the Health Promoting Lifestyle ProfileⅡ (HPLPⅡ). Latent profile analysis was used to classify the capability-opportunity-motivation-behavior characteristics of stroke patients, and multiple logistic regression was conducted to explore the influencing factors of different latent profiles.Results:Three latent profiles of capability-opportunity-motivation-behavior in stroke patients were identified, including low capability-opportunity-motivation-behavior with high health beliefs (32.4%, 193/596), moderate capability-opportunity-motivation-behavior with insufficient health beliefs (47.5%, 283/596), and high capability-opportunity-motivation-behavior with lack of social support (20.1%, 120/596). Multiple logistic regression analysis showed that educational level, smoking history, family history, body mass index, and Charlson Comorbidity Index score were influencing factors of different latent profiles ( P<0.05) . Conclusions:Stroke patients exhibit distinct classifications of capability-opportunity-motivation-behavior. Targeted interventions should be conducted based on the characteristics of each category to improve health behavior management outcomes in patients.