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Osteoarthritis （OA）， rheumatoid arthritis （RA）， gouty arthritis （GA）， and intervertebral disc degeneration （IVDD） are the most common bone and joint-related diseases in clinical practice. They can all affect related joints， leading to joint pain， swelling， dysfunction， and other symptoms. The difference is that OA is mainly caused by joint wear and age-related degradation and is manifested as joint pain， stiffness， and limited movement. RA is an autoimmune disease， manifested as joint pain， swelling， morning stiffness， and systemic symptoms. GA is caused by abnormal uric acid metabolism， manifested as acute arthritis， and IVDD is caused by intervertebral disc degeneration. Studies have shown that the mechanism of the occurrence and development of these bone and joint diseases is extremely complex. Pyroptosis is closely related to these bone and joint-related diseases by participating in bone and joint inflammation， cartilage metabolism imbalance， extracellular matrix degradation， and pathological damage of bone and joint. Inhibition of bone and joint-related pyroptosis will effectively prevent and treat bone and joint-related diseases. At the same time， many studies have confirmed that traditional Chinese medicine （TCM） has a prominent curative effect and obvious advantages in the prevention and treatment of bone and joint-related diseases. TCM can reduce the inflammatory reaction of bone and joints， improve the pathological damage of bone and joint diseases， and relieve bone and joint pain by inhibiting pyroptosis. Therefore， this article aims to briefly explain the relationship between pyroptosis and the occurrence and development of bone and joint-related diseases and summarize the latest research reports on the intervention of pyroptosis in the treatment of bone and joint-related diseases by TCM monomers， TCM extracts， and TCM compounds. It offers new ideas for the in-depth study of the pathogenesis and drug treatment of bone and joint diseases and provides a basis for the clinical use of TCM to prevent and treat bone and joint diseases.
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Osteoarthritis （OA） is a common chronic， highly prevalent， painful， and disabling degenerative joint disease. It has imposed a heavy burden on social healthcare and patients' psychology and economy due to its clinical symptoms such as impaired joint mobility and severe joint pain and the immature therapies. Studies have shown that OA is closely associated with articular cartilage dysfunction， synthesis and degradation disorders of chondrocyte extracellular matrix （ECM）， and joint inflammation. Moderate autophagy can restore the function of damaged chondrocytes， regulate chondrocyte apoptosis， and promote the synthesis and metabolism of ECM to alleviate the inflammation of joints and delay the onset and progression of OA. According to the clinical symptoms， OA can be classified into the category of impediment in traditional Chinese medicine. With the theories of holistic conception， treatment based on syndrome differentiation， and individualised diagnosis and treatment， traditional Chinese medicine has demonstrated definite effects in the treatment of OA in thousands of years of practice. Moreover， traditional Chinese medicine causes mild adverse reactions， and the patients have high tolerance and acceptance. This paper briefly explains the roles of autophagy and the related regulatory proteins， such as Unc-51-like autophagy-activated kinase 1 （ULK1）， Beclin-1， and microtubule-associated protein light chain 3 （LC3）， and details the latest research achievements in the prevention and control of OA by traditional Chinese medicines and its related markers via the regulation of autophagy， so as to provide a idea for the in-depth research in this field and the clinical application of traditional Chinese medicine in preventing and treating OA.
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Diabetic ulcer （DU） wound is one of the chronic and serious complications of diabetes characterized by prolonged wound healing， and it is more common in foot and lower extremity ulcers. DU has brought great economic and psychological pressure to patients and seriously affected the quality of life of patients because of its great difficulty in treatment， long treatment process， and high morbidity and mortality. Therefore， how to help the rapid healing of DU wounds， reduce the disability rate and mortality rate， protect limb function， and improve the quality of life is an important topic and hot spot in the field of medical research. The pathogenesis of DU is complex， mainly including microcirculation disorder， peripheral neuropathy， inflammation and infection， and excessive apoptosis of cells， involving physiological processes such as wound inflammation， granulation tissue hyperplasia and re-epithelialization. A large number of previous studies have found that Chinese medicine can regulate phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Wnt/β-catenin， nuclear factor-κB （NF-κB）， Notch， nuclear factor E2-related factor 2 （Nrf2）， transforming growth factor-β （TGF-β）/Smad， and other signaling pathways， regulate abnormal glucose metabolism， improve microcirculation， inhibit inflammation and oxidative stress， regulate cell proliferation and excessive apoptosis， and promote wound tissue growth to promote the rapid healing of DU wounds under the guidance of treatment based on traditional Chinese medicine （TCM） syndrome differentiation and internal and external treatment. Therefore， this paper reviewed Chinese medicinal monomers or Chinese medicinal compounds in recent years in regulating the above signaling pathways and the expression of key protein molecules and promoting the rapid healing of DU wounds， aiming to provide ideas and a theoretical basis for the in-depth study and clinical application of Chinese medicine in promoting the healing of DU wounds.
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Flap surgery is an important method to repair large open wounds in trauma and plastic surgery. However， flap necrosis is a common issue. Good blood circulation that provides nutrition is a necessary condition for the survival of the flap. Promoting revascularization， establishing blood circulation， and restoring blood perfusion as soon as possible after flap transplantation is crucial for flap survival. However， revascularization/blood reperfusion can cause flap ischemia-reperfusion injury （FIRI） after flap repair. If FIRI is not treated correctly and timely， it can cause flap necrosis and graft failure eventually. Previous studies have shown that the signaling pathways related to cell proliferation and apoptosis， such as the Notch signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， and inflammation-related pathways， such as nuclear factor E2-related factor 2 （Nrf2） signaling pathway， and nuclear factor-κB （NF-κB） signaling pathway can promote angiogenesis， improve local blood supply， inhibit the production and expression of inflammatory mediators， reduce oxidative stress and apoptosis， relieve ischemia-reperfusion injury （IRI）， and promote rapid healing after flap repair. By consulting a large number of modern medical research literature， this study reveals that both Chinese medicine monomers and Chinese medicine compounds can promote revascularization， restore blood perfusion， and accelerate healing after flap repair by regulating the expression of key protein molecules in the above-mentioned signaling pathways. This study summarized the research status in China and abroad， aiming to provide references for the in-depth study and clinical application of Chinese medicine to promote the healing of skin flaps after repair.
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Osteoporosis （OP）， a common systemic skeletal disease in the elderly， is characterised by bone loss and bone microstructural degeneration. Its clinical manifestations include increased bone fragility and bone pain. Furthermore， OP increases the risk of fracture due to the high bone fragility， which leads to lifelong disability or death， imposing a heavy economic and psychological burden on the patients and their families. The pathogenesis of OP is extremely complex and associated with a variety of factors such as proliferation and differentiation of osteoblasts， impairment of osteoclast activity and function， and abnormalities in autophagy activation. Recent studies have found that mammalian target of rapamycin （mTOR） signaing pathway is involved in the regulation of bone homeostasis， which can promote bone formation and improve bone metabolism and bone microstructure by regulating osteoblast proliferation and differentiation and osteoclast function and activating cellular autophagy， thus playing a crucial role in the prevention and treatment of OP. The prevention and treatment of OP with Chinese medicine has a long history， clear efficacy， multiple targets of action， low adverse effects， and wide medicine sources. Therefore， this paper briefly describes the role of mTOR signaling pathway in the development of OP by reviewing the latest research reports and summarizes in detail the latest research results on the treatment of OP with Chinese medicine extracts and prescriptions via the mTOR signaling pathway. This review aims to provide a basis for the in-depth research on the relationship between mTOR signaling pathway and OP and the clinical application of traditional Chinese medicine in the prevention and treatment of OP.
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The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.
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Diabetic neuropathic pain （DNP） is one of the common complications of diabetic peripheral neuropathy， which is difficult to be cured. The clinical manifestations of DNP include reduced pain threshold， neuropathic pain in extremities， and abnormal pain. Studies have demonstrated that nuclear factor-kappa B （NF-κB）， mitogen-activated protein kinase （MAPK）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathways are involved in the treatment of DNP by inhibiting the activation and release of inflammatory cytokines ［e.g.， tumor necrosis factor-alpha （TNF-α） and interleukin （IL）］， regulating inflammation-mediating factors ［e.g.， reactive oxygen （ROS）， inducible nitric oxide synthase （iNOS）， cyclooxygenase （COX-2）， and NF-κB inhibitor （IκB）］， suppressing neurogenic inflammation， destroying the persistent damage of peripheral nerves， and repairing damaged peripheral nerves. The literature of modern medical research has demonstrated that the treatment of DNP with Chinese herbal medicines is associated with the signaling pathways above. They can treat DNP by regulating the expression of key proteins in the signaling pathways to control neurogenic inflammation and repair diabetic peripheral neuropathic damage. By summarizing the available studies， this review aims to provide a reference for the in-depth research on Chinese herbal medicines in the treatment of DNP and give new insights into the protection of diabetic peripheral nerves and the treatment of DNP with Chinese herbal medicines.