Background: Chinese herbal pieces are an essential component of traditional Chinese medicine. Accurate identification and classification of these materials are crucial in clinical practice. Objective: This study aims to enhance the recognition efficiency of Chinese herbal pieces using deep learning technology, while addressing the limitations of traditional manual classification methods in terms of both quality and efficiency. Methods: A comprehensive dataset containing 201 types of Chinese herbal pieces was established. Based on Real-time Detection Transformer (RT-DETR), we designed and integrated a Feature-focused Diffusion Network (FDN), resulting in an improved model termed RT-DETR-FDN. The proposed FDN includes a Feature-focus Module and a feature diffusion mechanism, enabling the model to capture more extensive feature information from Chinese herbal pieces and diffuse it across multiple detection scales. Results: Experimental results show that RT-DETR-FDN achieved a precision of 0.925, a recall of 0.943, and an mAP50-95 of 0.851. In addition, the model was compared with representative You Only Look Once series models commonly used in object detection. Compared with these models, RT-DETR-FDN achieved higher recognition accuracy while maintaining a lightweight architecture. Conclusion: This study integrates deep learning with traditional Chinese medicine, providing a more effective solution for the recognition of Chinese herbal pieces.

Combined with elastic network model(ENM),the perturbation response scanning(PRS)has emerged as a robust technique for pinpointing allosteric interactions within proteins.Here,we proposed the PRS analysis of drug-target networks(DTNs),which could provide a promising avenue in network medicine.We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework,for drug repurposing of multiple sclerosis(MS).First,the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes.Then,based on topological analysis and functional annotation,the neurotransmission module was identified as the"therapeutic module"of MS.Further,perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis,giving a list of repurposable drugs for MS.Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of se-rotonin 2B receptor(HTR2B).Finally,we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex.These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS.As a useful systematic method,our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

Calcitonin gene-related peptides(CGRP)are peptides that are ubiquitous in the central and peripheral nervous systems,which has been shown to be associated with pain,setting off a boom in the development of chemical small molecule antagonists targeting CGRP receptors,but most of them have failed due to greater hepatotoxicity.Anti-CGRP/CGRPR antibodies have attracted widespread attention due to their high specificity and safety,especially lower hepatotoxicity.This article reviews the structure and function of CGRP and its receptors,as well as the research progress of anti-CGRP-related neutralizing antibodies in order to provide a reference for the exploration of disease mechanisms and drug development related to CGRP.

Objective Itproposes a WISN staffing demand model for clinical physicians to address the challenge that current physicians staffing standards fail to meet the operational needs of general hospitals.Methods Collect the 2023 annual operation data of a tertiary general hospital,using inpatient visits and surgeries as benchmarks to measure the workload demands of physicians in internal medicine and surgery,respectively.Additionally,integrate non-clinical workloads of physicians and the workload of resident physicians in standardized training to address the limitation of traditional models that focus solely on clinical tasks.Results The good applicability and robustness of the model in practical applications are verified through model comparison and sensitivity analysis,accurately reflecting the demand for physicians.Conclusion The model accurately reflects the workload of physicians in general hospitals,providing a quantitative estimation formula for physicians staffing.It has broad applicability and significant potential for wider adoption.

Combined with elastic network model (ENM), the perturbation response scanning (PRS) has emerged as a robust technique for pinpointing allosteric interactions within proteins. Here, we proposed the PRS analysis of drug-target networks (DTNs), which could provide a promising avenue in network medicine. We demonstrated the utility of the method by introducing a deep learning and network perturbation-based framework, for drug repurposing of multiple sclerosis (MS). First, the MS comorbidity network was constructed by performing a random walk with restart algorithm based on shared genes between MS and other diseases as seed nodes. Then, based on topological analysis and functional annotation, the neurotransmission module was identified as the "therapeutic module" of MS. Further, perturbation scores of drugs on the module were calculated by constructing the DTN and introducing the PRS analysis, giving a list of repurposable drugs for MS. Mechanism of action analysis both at pathway and structural levels screened dihydroergocristine as a candidate drug of MS by targeting a serotonin receptor of serotonin 2B receptor (HTR2B). Finally, we established a cuprizone-induced chronic mouse model to evaluate the alteration of HTR2B in mouse brain regions and observed that HTR2B was significantly reduced in the cuprizone-induced mouse cortex. These findings proved that the network perturbation modeling is a promising avenue for drug repurposing of MS. As a useful systematic method, our approach can also be used to discover the new molecular mechanism and provide effective candidate drugs for other complex diseases.

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

Drug-induced liver injury(DILI)is a common adverse drug reaction in clinical practice,which can lead to acute liver failure and even death in severe cases.In recent years,with the continuous introduction of new drugs and the expansion of their usage,the incidence and mortality rates of DILI have shown an upward trend,posing significant challenges to public health and clinical treatment.Macrophages,as a crucial component of the innate immune system,exhibit high plasticity and heterogeneity.They can polarize into pro-inflammatory M1 type or anti-inflammatory M2 type in response to microenvironmental signals.Research has demonstrated that macrophage polarization plays a central regulatory role in the occurrence and progression of DILI by influencing various processes such as inflammatory responses,cell apoptosis,and tissue repair.This review focuses on elucidating the regulatory mechanisms and roles of macrophage polarization in DILI,providing a theoretical framework for developing precise immunotherapeutic strategies.

Aim To investigate the protective effect of liraglutide(LIRA)on acetaminophen(APAP)-in-duced hepatotoxicity at the in vivo level and to reveal the underlying mechanism.Methods Forty SPF grade male C57BL/6J mice were randomly divided into the Control,LIRA(200 μg·kg-1),APAP(500 mg·kg-1),LIRA+APAP,LIRA+APAP+3-methylade-nine(3-MA,30 mg·kg-1)groups,with eight mice in each group.The mice were administered for three con-secutive days,and the materials were taken after 24 h.The general condition and body weight of mice in each group were recorded,and liver morphology was ob-served.Serum ALT and AST levels,as well as SOD ac-tivity,MDA,and GSH content in liver homogenates,were measured using biochemical assay kits.The levels of inflammatory cytokines IL-6,TNF-α,and IL-1β in serum were detected by ELISA.Liver pathological changes were assessed by HE staining,while mitochon-drial and autophagosome structures in liver tissues were observed using transmission electron microscopy.The number of PCNA-positive cells in liver tissues was e-valuated using immunohistochemical staining.The pro-tein expression levels of LC3Ⅱ,p62,Bax,Bcl-2,PC-NA,and CyclinD1 in liver tissues were determined by Western blot.Results LIRA pretreatment can im-prove the general condition of mice with acetamino-phen-induced liver injury(AILI),reduce serum ALT and AST levels,and effectively ameliorate the appear-ance and morphology of the liver as well as the patho-logical damage to liver tissue.Simultaneously,the lev-els of inflammatory cytokines IL-6,TNF-α,and IL-1βare significantly decreased;SOD activity and GSH con-tent are significantly increased,while MDA content is significantly reduced.Transmission electron microsco-py observations reveal the presence of numerous auto-phagosomes in the cytoplasm of liver tissue.Immuno-histochemical staining results indicate a significant in-crease in the number of PCNA-positive cells.Further-more,the expression of LC3Ⅱ,Bcl-2,PCNA,and Cy-clinD1 proteins in liver tissue is significantly upregulat-ed,while the expression of p62 and Bax proteins is significantly downregulated.However,after interven-tion with the autophagy inhibitor 3-MA,the aforemen-tioned protective effects of LIRA are significantly.Conclusions LIRA pretreatment can significantly im-prove liver injury in AILI mice.Its protective mecha-nism may be related to enhancing autophagy in hepato-cytes,thereby reducing oxidative stress,inflammatory response and apoptosis in liver of AILI mice.

Bronchial asthma is a heterogeneous chronic inflammatory airway disease.Its pathogenesis is closely associated with abnormal immune responses within T-helper(Th)cell subsets,characterized by excessive effector Th cell activation and impaired immunosuppression by regulatory T cells.The concept of natural harmony of yin-yang epitomizes the understanding of traditional Chinese medicine(TCM)of the body's inherent capacity for autonomous regulation and homeostasis maintenance.Building upon the description in the Inner Canon of Yellow Emperor regarding asthma as"internal yin qi contention,external yang qi interference,"this study aims to bridge the TCM macro-level etiology and pathogenesis of"yin-yang disharmony"with the Western micro-level mechanism of loss of immune homeostasis control.The core pathogenesis of bronchial asthma involves yin-yang disorder in the body,leading to internal-external imbalance.Yang deficiency with a hidden yin pathogen and intermingled phlegm with blood stasis in the lungs is the root of pathogenesis.Pathogenic invading qi and yang hyperactivity induce bronchial asthma.These align with the Western medical concepts of imbalanced immunometabolic self-stabilization and defective immunotolerance.Based on the above content,corresponding therapeutic principles are proposed according to the disease stage.In the acute phase,dispelling wind pathogens and relieving cough are recommended.In chronic persistent asthma,calming yang disturbance and resolving the yin conflict are emphasized.In the clinical remission phase,kidney yang should be warmed and invigorated,thereby consolidating body resistance.The corresponding treatment methods are implemented based on the above content.In the acute phase,self-made Mahuang Qingyang Decoction is administered to dispel wind pathogens and ventilate lung qi.In chronic persistent asthma,self-made Qingfei Xiegan Decoction is administered to clear liver-fire and purge the lungs,self-made Xuanfu Qingwei Decoction is employed to harmonize the stomach for descending adverse yang qi,modified Suzi Jiangqi Decoction is applied to conduct deficient yang back to its source,and modified Erchen Decoction and Taohong Siwu Decoction are utilized to expel phlegm and blood stasis.In the clinical remission phase,modified Sijunzi Decoction,modified Mahuang Fuzi Xixin Decoction,and Erxian Decoction are administered to invigorate the spleen and kidney.These approaches ward off yang disturbance and resolve yin contention to restore the body's normal immune homeostasis.The ultimate therapeutic aim is to achieve a state of natural harmony of yin-yang,thereby ceasing wheezing and coughing spontaneously,and to provide new ideas for clinical treatment of bronchial asthma.

Bronchial asthma is a heterogeneous chronic inflammatory airway disease.Its pathogenesis is closely associated with abnormal immune responses within T-helper(Th)cell subsets,characterized by excessive effector Th cell activation and impaired immunosuppression by regulatory T cells.The concept of natural harmony of yin-yang epitomizes the understanding of traditional Chinese medicine(TCM)of the body's inherent capacity for autonomous regulation and homeostasis maintenance.Building upon the description in the Inner Canon of Yellow Emperor regarding asthma as"internal yin qi contention,external yang qi interference,"this study aims to bridge the TCM macro-level etiology and pathogenesis of"yin-yang disharmony"with the Western micro-level mechanism of loss of immune homeostasis control.The core pathogenesis of bronchial asthma involves yin-yang disorder in the body,leading to internal-external imbalance.Yang deficiency with a hidden yin pathogen and intermingled phlegm with blood stasis in the lungs is the root of pathogenesis.Pathogenic invading qi and yang hyperactivity induce bronchial asthma.These align with the Western medical concepts of imbalanced immunometabolic self-stabilization and defective immunotolerance.Based on the above content,corresponding therapeutic principles are proposed according to the disease stage.In the acute phase,dispelling wind pathogens and relieving cough are recommended.In chronic persistent asthma,calming yang disturbance and resolving the yin conflict are emphasized.In the clinical remission phase,kidney yang should be warmed and invigorated,thereby consolidating body resistance.The corresponding treatment methods are implemented based on the above content.In the acute phase,self-made Mahuang Qingyang Decoction is administered to dispel wind pathogens and ventilate lung qi.In chronic persistent asthma,self-made Qingfei Xiegan Decoction is administered to clear liver-fire and purge the lungs,self-made Xuanfu Qingwei Decoction is employed to harmonize the stomach for descending adverse yang qi,modified Suzi Jiangqi Decoction is applied to conduct deficient yang back to its source,and modified Erchen Decoction and Taohong Siwu Decoction are utilized to expel phlegm and blood stasis.In the clinical remission phase,modified Sijunzi Decoction,modified Mahuang Fuzi Xixin Decoction,and Erxian Decoction are administered to invigorate the spleen and kidney.These approaches ward off yang disturbance and resolve yin contention to restore the body's normal immune homeostasis.The ultimate therapeutic aim is to achieve a state of natural harmony of yin-yang,thereby ceasing wheezing and coughing spontaneously,and to provide new ideas for clinical treatment of bronchial asthma.