ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

Chronic heart failure （CHF） represents the terminal stage of numerous cardiovascular diseases. According to traditional Chinese medicine theory， the pathogenesis of CHF is characterized by deficiency of the root and excess of the branch. The deficiency of the root mainly stems from insufficiency of heart Qi， while the excess of the branch arises from pathological accumulation of phlegm， blood stasis， and fluid retention. During the occurrence and development of CHF， the disobedience of heart Qi consistently serves as the key to the onset of the disease. As elucidated in Da Lun Chapter of WU Yun Xing in The Yellow Emperor's Inner Classic： Plain Questions， "harmony when conforming to qi and illness when going against Qi". This principle describes the relationship between human physiology and nature Qi dynamics. Harmony leads to health， while disobedience leads to illness. The same principle can be applied within the human body， that is， harmony between the zang-fu organs and their Qi leads to health， while disobedience leads to illness. The occurrence of CHF and the relationship between the heart and heart Qi also follow this principle. This study started from this theory， analyzed the relationship between "following or going against Qi" and the occurrence of diseases in the human body， further analyzing the "following" and "going against" between the heart and heart Qi， the pathogenesis of CHF， the corresponding relationship between the heart Qi and modern physiology in the state of "following Qi"， the corresponding situation between the heart Qi and modern pathology in the state of "going against Qi"， and the relationship between "going against Qi" and different stages of CHF. Moreover， it proposed to treat CHF from the perspective of "illness when going against Qi". One is to replenish the insufficiency of heart Qi （tonifying heart Qi and also invigorating the spleen）， and the other is to unblock the channels of heart Qi （resolving phlegm and removing turbidity to unblock the channels， removing blood stasis and dredging collaterals to promote blood circulation， and transforming fluid retention and expelling water to facilitate blood flow）. Meanwhile， the effects of single-herb Chinese medicines and Chinese-medicine compound prescriptions on the myocardium and micro-indexes of the human body under the "tonifying" and "unblocking" methods were analyzed. Through the above-mentioned treatment methods， the nature of heart Qi can finally be restored to "abundant" and "unobstructed"， so that the heart Qi can be harmonized and CHF can be improved. These findings may provide a new way of thinking for the future treatment of CHF.

ObjectiveTo investigate the effects of the classical Chinese medicine compound prescription Erjingwan on the inflammatory response and apoptosis of skeletal muscle cells in a mouse model of sarcopenia and decipher the mechanism based on the silent information regulator 1 （SIRT1）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） signaling pathway. MethodsForty C57/BL6 male mice were randomized into a control group， a model group， and groups with different doses of Erjingwan （8，16，32 g·kg^-1）. The mouse model of sarcopenia was established by D-gal-induced skeletal muscle senescence. The body weight and grip strength of mice treated with different doses of Erjingwan were examined to evaluate their physiological functions. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes and fibrosis in the skeletal muscle of mice. Enzyme-linked immunosorbent assay （ELISA） was adopted to determine the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum samples of mice， and biochemical tests were conducted to quantify the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione （GSH） in the serum. The protein and mRNA levels of SIRT1， Nrf2， B-cell lymphoma （Bcl-2）， and Bcl-2-associated X protein （Bax） were determined by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultsAfter 4 weeks of drug intervention， the model group exhibited significant reductions in body weight and grip strength （P0.01） compared with the control group. Compared with the model group， all doses of Erjingwan increased the body weight in mice at week 8 （P0.01） and grip strength from week 6 （P0.01）. HE staining revealed clear muscle fiber structure in the control group， muscle fiber rupture and atrophy in the model group， and dose-dependent repair of muscle fiber structure in the Erjingwan groups. Masson staining showed minimal collagen fibers and mild fibrosis in the control group， collagen fiber proliferation and severe fibrosis in the model group， and collagen proliferation with dose-dependent inhibition of fibrosis in the Erjingwan groups. ELISA results showed that serum levels of TNF-α and IL-6 were elevated in the model group compared with those in the control group （P0.01）. After intervention， the low-dose Erjingwan group exhibited a decreased TNF-α level （P0.05）， while the medium and high-dose groups showed decreases in both TNF-α and IL-6 levels （P0.01）. Biochemical assays revealed that the model group had decreased SOD and GSH levels （P0.01） and an increased MDA level （P0.01） compared with the control group. The medium and high-dose Erjingwan groups exhibited increases in SOD and GSH levels （P0.01） and decreases in MDA level （P0.01）， compared with the model group. WB and Real-time PCR results showed that compared with the control group， the model group presented down-regulated protein and mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 in the muscle tissue （P0.01） and up-regulated protein and mRNA levels of Bax （P0.01）. Compared with the model group， Erjingwan at different doses up-regulated the protein levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01） and down-regulated the protein and mRNA levels of Bax （P0.01） in the muscle tissue. Low-dose Erjingwan elevated the mRNA levels of Nrf2 and HO-1 （P0.05， P0.01）， and medium and high-dose Erjingwan up-regulated the mRNA levels of SIRT1， Nrf2， HO-1， and Bcl-2 （P0.01）. ConclusionErjingwan reduced the content of inflammatory factors in skeletal muscle cells， improved the antioxidant capacity， and attenuated pathological changes and fibrosis in the muscle of the mouse model of sarcopenia by regulating the SIRT1/Nrf2/HO-1 pathway， inflammatory response， and apoptosis network.

Chronic heart failure （CHF） represents the terminal stage of numerous cardiovascular diseases. According to traditional Chinese medicine theory， the pathogenesis of CHF is characterized by deficiency of the root and excess of the branch. The deficiency of the root mainly stems from insufficiency of heart Qi， while the excess of the branch arises from pathological accumulation of phlegm， blood stasis， and fluid retention. During the occurrence and development of CHF， the disobedience of heart Qi consistently serves as the key to the onset of the disease. As elucidated in Da Lun Chapter of WU Yun Xing in The Yellow Emperor's Inner Classic： Plain Questions， "harmony when conforming to qi and illness when going against Qi". This principle describes the relationship between human physiology and nature Qi dynamics. Harmony leads to health， while disobedience leads to illness. The same principle can be applied within the human body， that is， harmony between the zang-fu organs and their Qi leads to health， while disobedience leads to illness. The occurrence of CHF and the relationship between the heart and heart Qi also follow this principle. This study started from this theory， analyzed the relationship between "following or going against Qi" and the occurrence of diseases in the human body， further analyzing the "following" and "going against" between the heart and heart Qi， the pathogenesis of CHF， the corresponding relationship between the heart Qi and modern physiology in the state of "following Qi"， the corresponding situation between the heart Qi and modern pathology in the state of "going against Qi"， and the relationship between "going against Qi" and different stages of CHF. Moreover， it proposed to treat CHF from the perspective of "illness when going against Qi". One is to replenish the insufficiency of heart Qi （tonifying heart Qi and also invigorating the spleen）， and the other is to unblock the channels of heart Qi （resolving phlegm and removing turbidity to unblock the channels， removing blood stasis and dredging collaterals to promote blood circulation， and transforming fluid retention and expelling water to facilitate blood flow）. Meanwhile， the effects of single-herb Chinese medicines and Chinese-medicine compound prescriptions on the myocardium and micro-indexes of the human body under the "tonifying" and "unblocking" methods were analyzed. Through the above-mentioned treatment methods， the nature of heart Qi can finally be restored to "abundant" and "unobstructed"， so that the heart Qi can be harmonized and CHF can be improved. These findings may provide a new way of thinking for the future treatment of CHF.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

Radiotherapy is a cornerstone in the treatment of malignant tumors. It induces DNA damage through high-energy radiation, preferentially eliminating rapidly proliferating tumor cells. However, its clinical efficacy is often limited by tumor radioresistance and collateral damage to normal tissues. Consequently, elucidating the cellular response mechanisms to radiation stress and identifying key targets that can both sensitize tumor cells and protect normal tissues have become critical strategies for improving radiotherapy outcomes. Radiation stress triggers structural remodeling of the nucleolus, leading to the dissociation of certain ribosomal proteins from the ribosome and enabling them to acquire extra-ribosomal functions. Among these, RPL11 can be released and specifically binds to MDM2, thus inhibiting its E3 ubiquitin ligase activity, stabilizing p53, and mediating cell cycle arrest and apoptosis. The RPL11-MDM2-p53 pathway, acting as a signaling hub that links nucleolar dysfunction to cell fate determination, plays a pivotal role in maintaining genomic stability and regulating cellular responses to radiation. This review first introduces the basic characteristics of RPL11 and elucidates the molecular basis of radiation-induced ribosomal stress. It then outlines the core regulatory mechanisms of the cell cycle. On this basis, it focuses on the mechanisms by which radiation-induced RPL11 regulates the cell cycle and analyzes the specific effects of RPL11 on cell cycle. Furthermore, it discusses the role of the RPL11-MDM2-p53 pathway in cell cycle regulation. Finally, it explores the role of this pathway in maintaining genomic stability and determining cell fate, and highlights its potential value as a target for radiosensitization, aiming to provide new perspectives for enhancing tumor radiosensitivity and reducing damage to normal tissues.

OBJECTIVE: To observe the effects of moxibustion at different temperatures on cognitive function and blood glucose levels in patients with cognitive impairment associated with type 2 diabetes mellitus (T2DM). METHODS: A total of 66 T2DM patients with cognitive impairment were randomly assigned to a high-temperature group (22 cases, 1 case dropped out, 1 case was eliminated), a medium-temperature group (22 cases, 2 cases were eliminated), and a low-temperature group (22 cases, 2 cases were eliminated). All groups received moxibustion at Baihui (GV20), Dazhui (GV14), and Shenting (GV24) based on their existing glycemic control treatment. Moxibustion temperatures were maintained at 44-46 ℃ (high-temperature group), 41-43 ℃ (medium-temperature group), and 38-40 ℃ (low-temperature group), respectively, for 20 min per session, every other day, 3 times a week for 3 months. The Montreal cognitive assessment (MoCA) score, mini-mental state examination (MMSE) score, short-term memory (STM) accuracy and average reaction time, Rey-Osterrieth complex figure (ROCF) score, fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) were assessed before and after treatment. Clinical efficacy was evaluated after treatment. RESULTS: After treatment, MMSE scores in all three groups were higher than those before treatment (P<0.05). In the high-temperature group, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, naming, language, and abstraction were higher than those before treatment (P<0.05); the scores of ROCF copy, immediate recall, and delayed recall were higher than those before treatment (P<0.05); the HbA1c level was lower than that before treatment (P<0.05). In the medium-temperature group, the total MoCA score and the scores of memory and delayed recall, attention, and language were higher than those before treatment (P<0.05). STM accuracy was higher than before treatment (P<0.05), and STM average reaction time was shorter than before treatment (P<0.05) in both the high-temperature and medium-temperature groups. After treatment, the total MoCA score and the scores of visuospatial and executive function, memory and delayed recall, attention, and language in the high-temperature group were higher than those in the medium- and low-temperature groups (P<0.05); MMSE score, STM accuracy, and ROCF immediate recall and delayed recall scores were higher than those in the medium- and low-temperature groups (P<0.05); STM average reaction time was shorter than that in the medium- and low-temperature groups (P<0.05); HbA1c level was lower than that in the low-temperature group (P<0.05). The total MoCA score, attention score, and MMSE score in the medium-temperature group were higher than those in the low-temperature group (P<0.05), and STM average reaction time was shorter than that in the low-temperature group (P<0.05). There were no statistically significant differences in FPG within or between the three groups before and after treatment (P>0.05). The total effective rates were 75.0% (15/20) in the high-temperature group, 50.0% (10/20) in the medium-temperature group, and 15.0% (3/20) in the low-temperature group; the total effective rate in the high-temperature group was significantly higher than that in the low-temperature group (P<0.05). CONCLUSION Moxibustion at different temperatures has a dose-effect relationship in treating cognitive impairment in T2DM patients. A temperature range of 44-46 ℃ is more effective in improving cognitive function and stabilizing average blood glucose levels over 2-3 months.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Male ; Female ; Moxibustion ; Middle Aged ; Aged ; Cognitive Dysfunction/psychology* ; Cognition ; Temperature ; Blood Glucose/metabolism* ; Adult ; Acupuncture Points