ObjectiveTo explore the potential mechanisms of action of the modified Duhuo Jisheng Mixture （JDJM） in treating synovial lesions in knee osteoarthritis （KOA）. MethodsA total of 43 male New Zealand white rabbits were randomly allocated into a blank group （n=8） and a model group （n=35）. The KOA model was induced by immobilizing the right hind limb with a high-molecular resin plaster bandage， with a modeling period of 6 weeks， resulting in successful modeling in 32 rabbits. These rabbits were then randomly allocated to the model group， celecoxib group， JDJM group and JDJM+740Y-P group， each consisting of 8 rabbits. The celecoxib group received celecoxib via gavage at a single dose of 0.009 3 g·kg^-1， while the JDJM was administered a single dose of 6.8 mL·kg^-1 （4.515 2 g·kg^-1） of the herbal preparation via gavage. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） pathway activator + JDJM group received 4.515 2 g·kg^-1 of the herbal preparation via gavage along with an auricular vein injection of 0.15 μmol·kg^-1 740Y-P. For a period of 6 weeks， the remaining groups received an equal volume of physiological saline via gavage daily. After the medication period， the knee joint pain threshold and circumference were measured， and hematoxylin-eosin （HE） staining was performed to assess the pathological changes in the synovial tissues. Enzyme-linked immunosorbent assay （ELISA） measured the levels of interleukin-1β （IL-1β）， interleukin-6 （IL-18） and tumor necrosis factor-α （TNF-α） in the joint fluid. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， NOD-like receptor protein 3 （NLRP3）， cysteine-requiring aspartate protease-1 （Caspase-1） and gasdermin D （GSDMD） in the synovial tissues. Immunohistochemical （IHC） assay was performed to assess the protein expression of NLRP3， Caspase-1 and GSDMD. Western blot was carried out to analyze the protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD. ResultsCompared to the blank group， the model group showed a significant increase in knee joint circumference and decrease in pain threshold， the synovial tissue pathology score was higher （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid significantly increased （P<0.01）. PI3K， Akt， mTOR phosphorylation as well as mRNA and protein expression increased （P<0.01）， while the mRNA and protein expression levels of NLRP3， Caspase-1 and GSDMD also significantly increased （P<0.01）. Compared to the model group， the celecoxib and JDJM groups exhibited a significant reduction in knee joint circumference and increase in pain threshold， the synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid decreased （P<0.01）. The mRNA and protein expression of p-PI3K， p-Akt， p-mTOR， NLRP3， Caspase-1 and GSDMD were reduced （P<0.01）. Compared to the JDJM group， the JDJM+740Y-P group showed a decrease in the improvement of synovial lesions， an increase in knee joint circumference， and a decrease in pain threshold. The synovial tissue pathology score was lower （P<0.05）， and the levels of IL-1β， IL-18， and TNF-α in the joint fluid were higher （P<0.01）. The mRNA and protein expression of p-PI3K/PI3K， p-Akt/Akt， p-mTOR/mTOR， NLRP3， Caspase-1 and GSDMD increased （P<0.01）. ConclusionJDJM is effective in treating KOA. Its mechanism may involve modulating the PI3K/Akt/mTOR pathway in synovial tissues， inhibiting pyroptosis， reducing inflammatory factor release， and protecting bony structures.

There is a close relationship between subchondral bone remodeling and angiogenesis in knee osteoarthritis(KOA).Type H vessels,a newly identified subtype of bone vasculature,play a pivotal role in linking angiogenesis with osteogenesis by mediating signals through various cytokines,thereby regulating bone growth and homeostasis.During KOA development,mechanical loads and factors like transforming growth factor-β1(TGF-β1),platelet-derived growth factor-BB(PDGF-BB),vascular endothelial growth factor(VEGF)cause abnormal H-type vessel growth in subchondral bone and cartilage.This suggests that H-type vessel regulation might be a potential KOA treatment mechanism.This article explores the role of H-type vessels in subchondral bone remodeling and cartilage degeneration and the factors driving their abnormal growth,which provides a theoretical basis for further research and high-lights the potential of targeting H-type vessels for KOA treatment.

OBJECTIVES: To explore the mechanism by which histone deacetylase 1 (HDAC1) regulates steroid-induced apoptosis of mouse osteocyte-like MLO-Y4 cells. METHODS: MLY-O4 cells were treated with 400 nmol/L trichostatin A (TSA) or 1 mmol/L dexamethasone for 24 h or transfected with a HDAC1-overexpressing vector prior to TSA or dexamethasone treatment. The changes in the expressions of HDAC1, SP1, cleaved caspase-3 and Bax, SP1 acetylation level, cell proliferation, and cell apoptosis were examined. The interaction between HDAC1 and SP1 was determined with immunoprecipitation assay and Western blotting. RESULTS: Treatment with dexamethasone significantly increased cell apoptosis, enhanced the expressions of cleaved caspase-3 and Bax, reduced HDAC1 expression, and suppressed proliferation of MLO-Y4 cells. Both TSA and dexamethasone obviously increased SP1 acetylation level and the expression of SP1 in MLO-Y4 cells. HDAC1 overexpression in the cells significantly attenuated the effect of TSA and dexamethasone, promoted cell proliferation, lowered the expressions of SP1, cleaved caspase-3 and Bax, and inhibited dexamethasone-induced cell apoptosis. Immunoprecipitation assay and Western blotting demonstrated the interaction between HDAC1 and SP1 in the cells. CONCLUSIONS HDAC1 inhibits dexamethasone-induced apoptosis and promotes proliferation of cultured mouse osteocytes by suppressing SP1 expression via promoting its deacetylation.
Animals ; Apoptosis/drug effects* ; Mice ; Histone Deacetylase 1/genetics* ; Osteocytes/drug effects* ; Sp1 Transcription Factor/metabolism* ; Acetylation ; Dexamethasone/pharmacology* ; Cell Proliferation/drug effects* ; Caspase 3/metabolism* ; Cell Line ; Hydroxamic Acids/pharmacology* ; bcl-2-Associated X Protein/metabolism*

Allergic diseases,also known as hypersensitivity diseases,are a systemic disorder affecting nearly 40%of the global population.Although they vary in affected sites and clinical manifestations,they share many common features.For example,allergic diseases are the same type Ⅰ hypersensitivity reaction;the disease mechanism is based on the inability of the positive deficiency to resist the evil,and the allergens induce the onset of the disease;the course of the disease is similar to the patient's physique;the onset of the disease is closely related to the taiyin meridian of the hand and the foot;and the disease locations in traditional Chinese medicine can be categorized as the"orifices",so that the different diseases can be treated with the same treatment.Chinese medicine believes that spleen deficiency is the initiating factor of immune dysfunction,and lung deficiency is the key to the occurrence of allergic diseases,and regulating the lung and spleen is the key point of treatment for allergic diseases.The method of"cultivating the earth and generating gold"is good at adjusting the spleen and stomach and restoring the function of the lungs,which is the key to"same treatment for different diseases"of allergic diseases.Therefore,the purpose of this article is to explore the commonalities of allergic diseases and the role of the method of"cultivating the earth and generating gold"in the treatment of allergic diseases under the perspective of"same treatment for different diseases".

Objective To compare the early efficacy and safety of Huoluo Xiaotong capsules and Jingtong granules in treating cervical spondylosis radiculopathy(CSR).Methods A real-world study was conducted among CSR patients who visited three tertiary-grade-A hospitals in Changsha between January 2024 and February 2025.Patients were divided into a control group(Jingtong granules,4 g,po,tid)and an observation group(Huoluo Xiaotong capsules,1.4 g,po,tid);both groups were treated for 2 weeks.Baseline characteristics were balanced with inverse probability of treatment weighting(IPTW).Numeric rating scale(NRS)scores,overall response rates,and traditional Chinese medicine(TCM)symptom scores were compared at baseline,1 week,and 2 week.Results A total of 120 patients were ultimately included,with 30 in the control group and 90 in the observation group.After IPTW adjustment,at 1 week of treatment,the clinical efficacy rate of observation group(98.85％)were significantly exceeded that of control group(80.14％)(P＜0.001);at 2 weeks,the clinical efficacy rate of the two groups were both 100.00％.NRS and TCM syndrome scores showed no intergroup differences at baseline or 1 week(P＞0.05),at 2 weeks,the observation group demonstrated significantly lower NRS and TCM syndrome scores versus controls(P＜0.001).No adverse reactions occurred in either group.Conclusion Huoluo Xiaotong capsules demonstrate favorable short-term efficacy and safety in CSR,significantly alleviating pain and improving TCM symptoms within 2 weeks.High-quality randomized controlled trials are warranted to confirm these findings.

Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.

Allergic diseases,also known as hypersensitivity diseases,are a systemic disorder affecting nearly 40%of the global population.Although they vary in affected sites and clinical manifestations,they share many common features.For example,allergic diseases are the same type Ⅰ hypersensitivity reaction;the disease mechanism is based on the inability of the positive deficiency to resist the evil,and the allergens induce the onset of the disease;the course of the disease is similar to the patient's physique;the onset of the disease is closely related to the taiyin meridian of the hand and the foot;and the disease locations in traditional Chinese medicine can be categorized as the"orifices",so that the different diseases can be treated with the same treatment.Chinese medicine believes that spleen deficiency is the initiating factor of immune dysfunction,and lung deficiency is the key to the occurrence of allergic diseases,and regulating the lung and spleen is the key point of treatment for allergic diseases.The method of"cultivating the earth and generating gold"is good at adjusting the spleen and stomach and restoring the function of the lungs,which is the key to"same treatment for different diseases"of allergic diseases.Therefore,the purpose of this article is to explore the commonalities of allergic diseases and the role of the method of"cultivating the earth and generating gold"in the treatment of allergic diseases under the perspective of"same treatment for different diseases".

Objective To compare the early efficacy and safety of Huoluo Xiaotong capsules and Jingtong granules in treating cervical spondylosis radiculopathy(CSR).Methods A real-world study was conducted among CSR patients who visited three tertiary-grade-A hospitals in Changsha between January 2024 and February 2025.Patients were divided into a control group(Jingtong granules,4 g,po,tid)and an observation group(Huoluo Xiaotong capsules,1.4 g,po,tid);both groups were treated for 2 weeks.Baseline characteristics were balanced with inverse probability of treatment weighting(IPTW).Numeric rating scale(NRS)scores,overall response rates,and traditional Chinese medicine(TCM)symptom scores were compared at baseline,1 week,and 2 week.Results A total of 120 patients were ultimately included,with 30 in the control group and 90 in the observation group.After IPTW adjustment,at 1 week of treatment,the clinical efficacy rate of observation group(98.85％)were significantly exceeded that of control group(80.14％)(P＜0.001);at 2 weeks,the clinical efficacy rate of the two groups were both 100.00％.NRS and TCM syndrome scores showed no intergroup differences at baseline or 1 week(P＞0.05),at 2 weeks,the observation group demonstrated significantly lower NRS and TCM syndrome scores versus controls(P＜0.001).No adverse reactions occurred in either group.Conclusion Huoluo Xiaotong capsules demonstrate favorable short-term efficacy and safety in CSR,significantly alleviating pain and improving TCM symptoms within 2 weeks.High-quality randomized controlled trials are warranted to confirm these findings.

Mitophagy,a critical regulator of knee joint homeostasis,its dysfunction can lead to pathological changes such as reactive oxygen species overproduction,calcium ion overload,and extracellular matrix degradation,inducing cartilage degeneration and serving as a key pathological mechanism of knee osteoarthritis(KOA)."Deficient qi stagnation"represents the core pathogenesis of KOA.Mitochondria,analogous in function to qi and serving as its microscopic manifestation,exhibit a high degree of congruence between mitophagy and the defensive functions of qi.Based on the pathogenic characteristics of"deficient qi stagnation"of KOA,and integrating modern medical explanations of mitophagy,this article believed that the deficiency of liver,spleen and kidney qi is the fundamental reason for the imbalance of mitochondrial autophagy in KOA,and the retention of pathogenic toxins is the key factor in the imbalance of mitochondrial autophagy.The basic treatment method of tonifying qi and strengthening the body,promoting blood circulation and promoting stagnation can provide clinical formula ideas for the TCM prevention and treatment of KOA.

Osteoarthritis is the most common degenerative disease in humans,the pathogenesis of which is still un-clear.Mitochondrial impairment dysfunction plays an important role in human aging and degenerative diseases,therefore main-taining mitochondrial functional homeostasis is a potential therapeutic target for OA.Mitophagy is a process of targeted clear-ance and phagocytic dysregulated or damaged mitochondria to maintain mitochondrial homeostasis,which suggests that the reg-ulation of mitophagy may be a potential mechanism of OA treatment.In this paper,through reviewing the recently published lit-erature about mitophagy and OA,the role of mitophagy in the pathogenesis of OA is discussed,providing theoretical research for mitophagy,and emphasizing the potential of targeting autophagy to treat degenerative joint diseases.