Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

ObjectiveThis study leverages structural data from antigen-antibody complexes of the influenza A virus neuraminidase (NA) protein to investigate the spatial recognition relationship between the antigenic epitopes and antibody paratopes. MethodsStructural data on NA protein antigen-antibody complexes were comprehensively collected from the SAbDab database, and processed to obtain the amino acid sequences and spatial distribution information on antigenic epitopes and corresponding antibody paratopes. Statistical analysis was conducted on the antibody sequences, frequency of use of genes, amino acid preferences, and the lengths of complementarity determining regions (CDR). Epitope hotspots for antibody binding were analyzed, and the spatial structural similarity of antibody paratopes was calculated and subjected to clustering, which allowed for a comprehensively exploration of the spatial recognition relationship between antigenic epitopes and antibodies. The specificity of antibodies targeting different antigenic epitope clusters was further validated through bio-layer interferometry (BLI) experiments. ResultsThe collected data revealed that the antigen-antibody complex structure data of influenza A virus NA protein in SAbDab database were mainly from H3N2, H7N9 and H1N1 subtypes. The hotspot regions of antigen epitopes were primarily located around the catalytic active site. The antibodies used for structural analysis were primarily derived from human and murine sources. Among murine antibodies, the most frequently used V-J gene combination was IGHV1-12*01/IGHJ2*01, while for human antibodies, the most common combination was IGHV1-69*01/IGHJ6*01. There were significant differences in the lengths and usage preferences of heavy chain CDR amino acids between antibodies that bind within the catalytic active site and those that bind to regions outside the catalytic active site. The results revealed that structurally similar antibodies could recognize the same epitopes, indicating a specific spatial recognition between antibody and antigen epitopes. Structural overlap in the binding regions was observed for antibodies with similar paratope structures, and the competitive binding of these antibodies to the epitope was confirmed through BLI experiments. ConclusionThe antigen epitopes of NA protein mainly ditributed around the catalytic active site and its surrounding loops. Spatial complementarity and electrostatic interactions play crucial roles in the recognition and binding of antibodies to antigenic epitopes in the catalytic region. There existed a spatial recognition relationship between antigens and antibodies that was independent of the uniqueness of antibody sequences, which means that antibodies with different sequences could potentially form similar local spatial structures and recognize the same epitopes.

ObjectiveTo systematically review the studies about Yiqing Capsules in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat-toxin syndrome and clarify the advantages and therapeutic characteristics of Yiqing capsules， thus providing reference for the decision-making by relevant departments and clues for the clinical and basic research. MethodThe multi-criteria decision analysis （MCDA） model and CSC v2.0 were employed to comprehensively evaluate Yiqing capsules from multiple aspects. ResultThe serious adverse reactions in the spontaneous reporting system （SRS） monitoring data of Yiqing capsules included pruritus， rash， an ddiarrhea， all of which were relieved or cured， without aggravation or interhospital transfer for treatment. Literature data showed that the main clinical adverse reactions were abdominal pain， diarrhea， etc. Both acute toxicity and long-term toxicity tests showed good safety， and thus the safety of Yiqing capsules was rated as grade B. The results of Meta-analysis showed that Yiqing capsules used alone or in combination with other medicines outperformed Niuhuang Jiedu capsules or Western medicine in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat toxin in terms of symptom alleviation， disappearance rate of main symptoms， and recurrence rate of aphtha. Pharmacological and pharmacodynamic studies showed that Yiqing capsules had antimicrobial， antiviral， and anti-inflammatory effects， with the effectiveness rated as grade B. The decision tree model was adopted to analyze the incremental cost-effectiveness ratio. With the threshold of 1 fold per capita GDP and the disappearing rate of pain in gingivitis as the indicator， Yiqing capsules had an economic advantage in the treatment of gingivitis due to heat-toxin compared with Niuhuang Jiedu capsules， and the incremental cost-effectiveness ratio was 0.39 yuan/%， which indicated acceptable cost， with the economy rated as grade B. Yiqing capsules can not only clear heat from Qi aspect but also purge blood fire， serving as the representative prescription of clearing and purging for heat-toxin syndrome. Considering the industrial service system and enterprise innovation， the comprehensive innovation of Yiqing capsules was rated as grade B. Generally， this product does not require personalized treatment plans and features convenient supply， storage， transportation， policy publicity， drug information standards， and easy operation for medical care and patients. The Chinese patent medicine information was complete and in line with national standards， and thus the suitability of Yiqing capsules was rated as grade A. With a low price and good availability and affordability， the accessibility of Yiqing capsules was rated as grade A. The Yiqing capsules prescription， Sanhuang Xiexin decoction， originated from ancient medical books， with rich real-world studies， and thus the traditional Chinese medicine characteristics of Yiqing capsules was rated as grade C. ConclusionThe clinical value of Yiqing capsules was rated as grade B from the "6+1" dimensions， suggesting that it could be conditionally converted into the relevant policy results of basic clinical drug management according to the procedure.

Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.

Objective To study the effect of curcumin on wound healing in diabetic mice.Methods The effect of curcumin on fibroblast activity was examined by the MTT assay,and the ROS detection kit was used to detect the effect of curcumin on the hydrogen peroxide-induced scavenging effect of reactive oxygen species(ROS)in fibroblasts.Q-PCR was used to detect the effects of curcumin on the mRNA expression of inflammatory factors CD86,CD206,IL-6 and ARG1 in lipopolysaccharide-induced RAW 264.7macrophage.The wound model of diabetes was established by intraperitoneal injection of streptozotocin.Hematoxylin-eosin(HE)and Masson staining were used to evaluate wound healing and histomorphological changes,and immunofluorescence staining was used to determine skin tissue α-smooth muscle actin,CD86 and CD206 expression.Results Curcumin had no significant effect on fibroblast activity at concentrations less than 20 mol·L-1;curcumin scavenged hydrogen peroxide-induced intracellular ROS in fibroblasts;curcumin decreased the mRNA expression of CD86 and IL-6 while increasing CD206 and ARG1 in lipopolysaccharide-induced RAW 264.7 macrophages.After in vivo administration,compared with the control group,wound healing was significantly faster in the curcumin(15,30 mg·mL-1)group after 7 d and 14 d of wound perforation(P＜0.01).Hematoxylin-eosin(HE)and Masson staining results confirmed a significant increase in granulation tissue and a significant increase in collagen deposition in the curcumin(15,30 mg·mL-1)group.Immunofluorescence assay showed significantly higher expression of CD206(P＜0.01)and significantly reduced expression of CD86(P＜0.01)in the skin wounds of curcumin(15,30 mg·mL-1)for 14 d.In addition,the expression of α-SMA in the wound of the high-dose curcumin(30 mg·mL-1)group was significantly higher than that of the low-dose curcumin group(P＜0.01).Conclusion Curcumin accelerates diabetic wound healing by promoting granulation tissue proliferation and collagen deposition in refractory diabetic wounds in mice through its anti-inflammatory and antioxidant effects.

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Rheumatoid arthritis （RA） is a chronic autoimmune disease with a complex pathogenesis. Immune dysfunction， synovial inflammation， and bone destruction are the key pathological links. The theory of "harmful hyperactivity and responding inhibition" is a high-level summary of the coordinated development of things in nature and the generation and restriction of the five elements and the six factors in nature. People and all things have the same origin， and the theory of "harmful hyperactivity and responding inhibition" represents the intrinsic regulation mechanism of the human body's homeostasis， reflecting the unity of opposites of "hyperactivity" and "inhibition" and emphasizing coordination and stabilization. In the pathogenesis of RA， the excessive immune response disrupts the normal body balance， which is closely related to the process of "hyperactivity becoming harmful". Synovial inflammation， tissue hyperplasia， and bone destruction are pathological results of the dysregulation of the body's immune self-stabilization function and can be regarded as the process of "failing to inhibition". Therefore， the theory of "hyperactivity harmful hyperactivity and responding inhibition" provides a unique perspective for understanding the modern pathological mechanisms of RA. Based on the theory of "harmful hyperactivity and responding inhibition" and the pathogenesis of RA， the author analyzed the modern medical basis of RA from the perspective of traditional Chinese medicine （TCM） and revealed the intrinsic connection between TCM pathogenesis such as insufficiency of vital energy and blood， strong defensive Qi and weak nutrient Qi， and intertwined phlegm and blood stasis and modern research on autoimmune disorders， synovial inflammation， and bone destruction. With the therapeutic criterion of "harm inhibition and responsible supporting"， the article summarized the mechanism of TCM in calming hyperactivity and supporting invincibility， which provided theoretical references for the clinical treatment of RA.

Objective:To explore the material basis and potential mechanism of Sanhuang Yishen Capsules in the treatment of diabetes through network pharmacology, molecular docking and experimental verification.Methods:The active components and targets of Sanhuang Yishhen Capsules were screened using China Natural product chemical composition database and SymMap database, and the related targets of T2DM were screened by GeneCards database. The "Chinese materia medica-active component-target" network was constructed, and the intersection genes were enriched by GO and KEGG using R language. Key active components were selected for molecular docking verification with potential core targets. 60 rats were divided into normal group, model group, and Sanhuang Yishen Capsules group according to random number table method, with 15 rats in each group. In addition to the normal group, the diabetic rat model was prepared in the other groups, and the corresponding drugs were intragastric in each group for 8 weeks. The levels of fasting blood glucose (FBG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were measured by radioimmunoassay. Western blotting was used to detect protein expressions of epidermal growth factor receptor (EGFR), epidermal growth factor (EGF), Akt serine/threonine kinase 1 (AKT1), recombinant tumor protein p53 (TP53), and recombinant caspase 3 (CASP3).Results:A total of 160 active components and 298 targets of Sanhuang Yishen Capsules, 2194 targets related to T2DM, and 166 intersection targets were obtained. GO and KEGG analyzed a series of biological reaction processes mainly involved in signal transduction, oxidative stress, apoptosis, etc., and mainly involved in the regulation of P13K/Akt, P53, CASP3 and other targets. The results of molecular docking showed that the main active components obtained by screening had strong binding with the target. Compared with model group, FBG, FINS, HOMA-IR, TP53 and CASP3 in Sanhuang Yishen Capsules group decreased ( P<0.05), EGFR, EGF and Akt1 proteins increased ( P<0.05). Conclusion:The mechanism of Sanhuang Yishen Capsules for the treatment of may be related to the regulation of EGF/EGFR/P13K/Akt signaling pathway, TP53 signaling pathway, CASP3 signaling pathway, PPARG signaling pathway, ESR1 signaling pathway, PTGS2 signaling pathway, CAT signaling pathway and CTNNB1 signaling pathway.

Objective To evaluate the therapeutic effect of evodiamine(Evo)on atopic dermatitis(AD)in rat models by regulating the cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response ele-ment binding protein(CREB)signaling pathway.Methods A rat model of AD was established by administration of multiple doses of 2,4-dinitrochlorobenzene(DNCB).The animals were randomly divided into AD group,Evo-low-dose(Evo-L,5 mg/kg)group,Evo-high-dose(Evo-H,10 mg/kg)group,Evo-H+H-89(5 mg/kg)group and dexamethasone(0.1 mg/kg)group.Normal rats were used as the control group and then the degree of skin damage of rats in each group was scored.Abdominal blood was taken to detect the levels of interleukin-4(IL-4),cAMP,and tumor necrosis factor-α(TNF-α)in serum;Skin lesion tissue was collected to detect pathological change,counting of mast cells,PKA/CREB related protein expression and expression of IL-4 and TNF-α mRNA in the tissue.Results Compared with control group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions of AD group were reduced,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells and mRNA expression of IL-4 and TNF-α in skin lesion tissues were all significantly increased(P＜0.05).Compared with AD group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-L group,Evo-H group,and dexamethasone group were increased,the severity score of skin lesions,level of IL-4 and TNF-α,epidermal thickness,number of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues all reduced(P＜0.05).Compared with the Evo-H group,the level of cAMP in serum,the expression of p-PKA/PKA,and p-CREB/CREB in skin lesions in Evo-H+H-89 group was reduced and the severity score of skin lesion,level of IL-4 and TNF-α,epidermal thickness,num-ber of mast cells,and mRNA expression of IL-4 and TNF-α in skin lesion tissues significantly increased(P＜0.05).Conclusions Evo inhibits inflammatory response and pathological damage through regulation of cAMP/PKA/CREB signaling pathway in AD rat models.