ObjectiveTo explore the mechanism of herbal cake-separated moxibustion using the classical formula Xiaoyaosan in alleviating neuroimmune inflammatory responses in chronic fatigue syndrome （CFS） rats， based on the regulation of the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear transcription factor-κB （NF-κB） signaling pathway. MethodsFifty SPF-grade SD rats aged 6-8 weeks were randomly divided into five groups： Normal group， model group， sham herbal cake moxibustion group， Chinese medicine intragastric administration group， and herbal cake-separated moxibustion group， with 10 rats in each group. Except for the normal group， all other groups underwent a 21-day modeling process， followed by behavioral testing. The herbal cake-separated moxibustion and sham herbal cake moxibustion groups received interventions at the Shenque （CV8）， Guanyuan （CV4）， Zusanli （ST36）， and Qimen （LR14） acupoints. The Chinese medicine intragastric administration group was treated with a Xiaoyaosan suspension via gavage. Behavioral tests were conducted after 10 days of continuous intervention. Serum levels of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α）， as well as hippocampal levels of IL-1β， IL-6， TNF-α， and NF-κB， were detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the hippocampus were observed using hematoxylin-eosin （HE） staining. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of TLR4， MyD88， and NF-κB in the hippocampus. Western blot analysis was performed to detect the relative expression levels of TLR4， MyD88， NF-κB， and p65 proteins in the hippocampus. ResultsCompared with the normal group， the model group showed a significant decrease in upright times during the open field test （P<0.01）， as well as significant reductions in total movement distance， resting time， and center region duration （P<0.01）. In the tail suspension test， immobility time increased （P<0.01）， and struggle times decreased （P<0.01）. Serum and hippocampal levels of IL-1β， IL-6， and TNF-α， as well as hippocampal NF-κB levels and TLR4， MyD88， and NF-κB mRNA expression， were significantly elevated （P<0.01）. After treatment， compared with the model group， the total movement distance and upright times in the open field test were significantly increased in all treatment groups （P<0.01）， while resting time and center region duration were notably prolonged （P<0.05， P<0.01）. Immobility time in the tail suspension test was significantly shortened （P<0.01）， and struggle times significantly increased （P<0.05）. Serum and hippocampal levels of IL-1β， IL-6， TNF-α， hippocampal NF-κB levels， and TLR4 and NF-κB mRNA expression were significantly reduced （P<0.05， P<0.01）. Compared with the sham herbal cake moxibustion group， the herbal cake-separated moxibustion group showed a significant extension in center region duration during the open field test （P<0.05） and a significant increase in upright times （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum TNF-α levels in the Chinese medicine intragastric administration group were significantly reduced （P<0.01）， while serum IL-6 levels， as well as hippocampal levels of IL-1β， TNF-α， NF-κB， and TLR4， MyD88， and NF-κB mRNA expression， were significantly decreased in both the Chinese medicine intragastric administration group and the herbal cake-separated moxibustion group （P<0.05， P<0.01）. Compared with the Chinese medicine intragastric administration group， the herbal cake-separated moxibustion group exhibited significantly increased upright times in the open field test （P<0.01）. In the tail suspension test， immobility time was reduced （P<0.01）， and struggle times increased （P<0.01）. Serum IL-1β， hippocampal TNF-α levels， and TLR4， MyD88， and NF-κB mRNA expression were significantly decreased （P<0.05， P<0.01）. ConclusionHerbal cake-separated moxibustion effectively improves fatigue and memory function in CFS rats， regulates neuroimmune inflammatory responses， and its mechanism may be related to the modulation of the TLR4/MyD88/NF-κB signaling pathway.

Depression and circadian rhythms exhibit bidirectional interactions,suggesting a close association with the biological clock system.The biological clock in the suprachiasmatic nucleus of the hypothalamus is regulated by circadian genes.Recent clinical and basic research has revealed multifaceted associations between depression and circadian genes.For instance,significant phase abnormalities in BMAL1,PER2,and PER3 were detected in brain tissue from depressed patients,while plasma levels of CRY1,ARNTL,and PER1 proteins showed marked reduction,demonstrating good diagnostic value.Mice with CLOCK and BMAL1 knockouts exhibited depression-like behaviors.Single nucleotide polymorphisms(SNPs)in genes such as PER1 and PER3 directly influence depression susceptibility.Methylation levels of BMAL1,PER3,and CLOCK genes correlate closely with depressive symptoms.Antidepressant mechanisms like ketamine exert their effects by downregulating PER2 and other genes.This review summarizes the differential expression patterns of circadian clock genes in depression and associated therapeutic approaches,aiming to provide new theoretical foundations for precision diagnosis and personalized treatment strategies for depression.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

Parathyromegaly refers to chronic enlargement of the parathyroid glands caused by multiple etiological factors. Pathological conditions, such as hyperparathyroidism, parathyroid hyperfunction, parathyroid adenoma, parathyroid cysts, and parathyroid carcinoma may all lead to parathyromegaly. Notably, calcium intake insufficiency and/or vitamin D insufficiency (CVI), which is the predominant etiology of parathyromegaly, now has been recognized as a global public health challenge. Chronic CVI induces negative calcium balance and relative low serum calcium level, stimulating compensatory parathyroid hyperplasia and enlargement. This progression triggers parathyroid hyperfunction and secondary hyperparathyroidism, resulting in bone mass loss, height reduction, kyphosis, osteoporosis, pathological fractures, metastatic vascular calcification and systemic abnormal calcium migration and calcinosis (such as urolithiasis). During the early stages of parathyromegaly, the condition remains preventable and treatable; However, delayed intervention may lead to irreversible tertiary hyperparathyroidism. CVI-associated parathyromegaly exhibits high prevalence and heterogeneous clinical manifestations, representing a critically underrecognized clinical entity. This article will systematically discuss the etiology, pathological characteristics, clinical consequences, and prevention and control strategies for CVI-related parathyromegaly.

Patients with initially diagnosed breast cancer and uncontrolled hyperthyroidism are at high risk of perioperative thyroid crisis. This article reports two cases of early-stage breast cancer initially diagnosed concurrently with uncontrolled primary hyperthyroidism. In Case 1, the patient received neoadjuvant chemotherapy to control breast cancer progression while concurrently taking antithyroid drugs to manage hyperthyroidism. Hyperthyroidism was controlled during chemotherapy, and the patient successfully underwent surgery after neoadjuvant chemotherapy. Case 2 involved recurrent primary hyperthyroidism with leukopenia after antithyroid drug therapy. Since leukopenia is a relative contraindication for antithyroid drugs, the patient underwent radioactive iodine therapy (iodine-131) and endocrine therapy for one month before proceeding with breast cancer surgery. Through a literature review, this article analyzes preoperative management strategies for uncontrolled hyperthyroidism in initially diagnosed breast cancer patients, emphasizing the importance of normalizing thyroid function to prevent thyroid crisis and reduce perioperative risks.

The structure and potential antigenic epitopes of FliCEcN were analysed using bioinformat-ics technology.With the help of ClonExpress? homologous recombination technology,primers were designed to deletion of different structural domains in the highly variable region of FliCEcN and cloned into pET-28a(+)expression vector for expression.The expressed flagellin variants were identified by SDS-PAGE and Western blot.Endotoxin residues in the flagellin variants were detected by horseshoe crab reagent chromatography,and Caco-2 cells were stimulated with differ-ent concentrations of flagellin variants.The biological activity of each flagellin variant was assessed by detecting the secretion level of IL-8.Bioinformatic analysis showed that most of the structural domains in the highly variable region of FliCEcN were predicted to contain potential antigenic epitopes.PC R results showed that fliC△820-1 518,fliC△736-963,fliC△985-1 200,fliC △748-828,fliC△1 114-1 191,andfliC△1 225-1311 were approximately 1 095,1 566,1 578,1 713,1 716 and 1 707 bp,respectively.SDS-PAGE results showed that the sizes of the flagellin variants treated with nickel column purifi-cation and dialysis replication were about 41.36,57.06,57.50,61.97,61.95 and 61.56 kDa,respec-tively.Western blot results showed that all six flagellin variants reacted specifically with anti-His monoclonal antibody and E.coli H7 antigen diagnostic serum.The results of TLR5 activity assay showed that the flagellin variants missing different structural domains retained their TLR5 agonist function.In this study,six flagellin variants with different structural domains of FliCEcN deletion hypervariable region were successfully constructed,and all of them retained their TLR5 agonist function and showed good biological properties.This provides a reference for further research on the adjuvant effect of flagellin after deletion of different structural domains and the effect of flagel-lin antibody titer on its adjuvant effect.

Depression and circadian rhythms exhibit bidirectional interactions,suggesting a close association with the biological clock system.The biological clock in the suprachiasmatic nucleus of the hypothalamus is regulated by circadian genes.Recent clinical and basic research has revealed multifaceted associations between depression and circadian genes.For instance,significant phase abnormalities in BMAL1,PER2,and PER3 were detected in brain tissue from depressed patients,while plasma levels of CRY1,ARNTL,and PER1 proteins showed marked reduction,demonstrating good diagnostic value.Mice with CLOCK and BMAL1 knockouts exhibited depression-like behaviors.Single nucleotide polymorphisms(SNPs)in genes such as PER1 and PER3 directly influence depression susceptibility.Methylation levels of BMAL1,PER3,and CLOCK genes correlate closely with depressive symptoms.Antidepressant mechanisms like ketamine exert their effects by downregulating PER2 and other genes.This review summarizes the differential expression patterns of circadian clock genes in depression and associated therapeutic approaches,aiming to provide new theoretical foundations for precision diagnosis and personalized treatment strategies for depression.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

Parathyromegaly refers to chronic enlargement of the parathyroid glands caused by multiple etiological factors. Pathological conditions, such as hyperparathyroidism, parathyroid hyperfunction, parathyroid adenoma, parathyroid cysts, and parathyroid carcinoma may all lead to parathyromegaly. Notably, calcium intake insufficiency and/or vitamin D insufficiency (CVI), which is the predominant etiology of parathyromegaly, now has been recognized as a global public health challenge. Chronic CVI induces negative calcium balance and relative low serum calcium level, stimulating compensatory parathyroid hyperplasia and enlargement. This progression triggers parathyroid hyperfunction and secondary hyperparathyroidism, resulting in bone mass loss, height reduction, kyphosis, osteoporosis, pathological fractures, metastatic vascular calcification and systemic abnormal calcium migration and calcinosis (such as urolithiasis). During the early stages of parathyromegaly, the condition remains preventable and treatable; However, delayed intervention may lead to irreversible tertiary hyperparathyroidism. CVI-associated parathyromegaly exhibits high prevalence and heterogeneous clinical manifestations, representing a critically underrecognized clinical entity. This article will systematically discuss the etiology, pathological characteristics, clinical consequences, and prevention and control strategies for CVI-related parathyromegaly.

Patients with initially diagnosed breast cancer and uncontrolled hyperthyroidism are at high risk of perioperative thyroid crisis. This article reports two cases of early-stage breast cancer initially diagnosed concurrently with uncontrolled primary hyperthyroidism. In Case 1, the patient received neoadjuvant chemotherapy to control breast cancer progression while concurrently taking antithyroid drugs to manage hyperthyroidism. Hyperthyroidism was controlled during chemotherapy, and the patient successfully underwent surgery after neoadjuvant chemotherapy. Case 2 involved recurrent primary hyperthyroidism with leukopenia after antithyroid drug therapy. Since leukopenia is a relative contraindication for antithyroid drugs, the patient underwent radioactive iodine therapy (iodine-131) and endocrine therapy for one month before proceeding with breast cancer surgery. Through a literature review, this article analyzes preoperative management strategies for uncontrolled hyperthyroidism in initially diagnosed breast cancer patients, emphasizing the importance of normalizing thyroid function to prevent thyroid crisis and reduce perioperative risks.