1.Tangbikang Granules Improve Diabetic Peripheral Neuropathy by Inhibiting Ferroptosis via AMPK/Nrf2 Signaling Pathway
Zehong YANG ; Tonghua LIU ; Xiaohong MU ; Yaqi ZHANG ; Huizhong BAI ; Lingling QIN ; Xiaolei JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):52-60
ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty (ZDF) rats. After successful modeling, the rats were divided into a normal group, a model group, high-, medium-, and low-dose Tangbikang granules groups, and a metformin hydrochloride group. The high-, medium-, and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5, 1.25, 0.625 g·kg-1, respectively. The metformin hydrochloride group received 0.135 g·kg-1 by gavage, while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration, and at 4, 8, 12 weeks. Following the 12-week intervention, the thermal pain threshold and the sciatic nerve conduction velocity (SNCV) were measured. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), and adenosine triphosphate (ATP) in the sciatic nerve were measured using enzyme-linked immunosorbent assay (ELISA). Morphological changes in the sciatic nerve were observed using hematoxylin and eosin (HE) staining, and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 (GPx4) were detected using immunofluorescence (IF) assay. The protein expression levels of p-AMPK, Nrf2, GPx4, and acyl-CoA synthetase long-chain family member 4 (ACSL4) were detected using Western blot. ResultsCompared with the normal group, the model group had significantly higher blood glucose levels after administration and at weeks 4, 8 and 12 (P<0.01). The thermal pain threshold was significantly prolonged (P<0.01), and the SNCV was significantly slowed down (P<0.01). The SOD and ATP levels significantly decreased (P<0.01), while the MDA levels significantly increased (P<0.01). Pathologically, the sciatic nerve fibers in the model group showed a dispersed structure, disordered and sparse arrangement, axonal atrophy, irregular myelin sheath halo, increased and swollen Schwann cell nuclei, obvious endoneurial fibrosis, and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 (P<0.01). Western blot analysis showed significantly decreased protein expression levels of p-AMPK, Nrf2, and GPx4 (P<0.01), and significantly increased expression of ACSL4 (P<0.01) in the model group. Compared with the model group, fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 (P<0.05). The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups (P<0.01). The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups (P<0.01). The SOD levels were significantly elevated in the high-dose Tangbikang granules group (P<0.01). The MDA levels significantly decreased in all Tangbikang granules groups (P<0.01). Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups (P<0.01). The protein expression levels of p-AMPK, Nrf2, and GPx4 were significantly increased (P<0.01), while ACSL4 protein expression significantly decreased (P<0.01). ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.
2.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
3.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
4.Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
Lijia WU ; Chengfei ZHANG ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; Yukun HUANG ; You WANG ; Xincui BAO ; Jing YANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):60-69
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy (DPN) based on the glyoxalase-1 (GLO-1)/advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided, with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ) to induce a type 2 diabetes mellitus (T2DM) model. Based on blood glucose levels, the rats were randomly assigned to the model group, Tanglin group (13.5 mg·kg-1), metformin group (135 mg·kg-1), and Tangbikang dry paste low-, medium-, and high-dose groups (3, 6, 12 g·kg-1). Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose, body weight, and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention, the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin (HE) staining. The expression of RAGE, AGE, protein kinase C (PKC), and collagen (COL) in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE, PKC, Toll-like receptor (TLR), COL, and GLO-1 was detected using real-time quantitative PCR (Real-time PCR). Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CREA), urea (UREA), interleukin-6 (IL-6), and tumor necrosis factor (TNF)-α were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the normal group, the model group showed significantly increased fasting blood glucose (P<0.01), decreased body weight and mechanical pain threshold (P<0.01), and elevated serum AST, ALT, CREA, UREA, IL-6, and TNF-α levels (P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was significantly increased (P<0.01), while COL expression was decreased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was upregulated (P<0.01), whereas COL and GLO-1 mRNA levels were downregulated (P<0.01). Histological examination showed irregular nerve morphology, axonal alterations, and myelin degeneration. Compared with the model group, fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced (P<0.05, P<0.01). No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups (P<0.05, P<0.01). Serum IL-6 and TNF-α levels were decreased in all dose groups (P<0.05, P<0.01). The expression of RAGE, AGE, and PKC in the sciatic nerve was reduced (P<0.01), while COL expression was increased (P<0.01). The mRNA expression of TLR, RAGE, and PKC was downregulated (P<0.01), whereas GLO-1 mRNA expression was upregulated (P<0.05, P<0.01). Additionally, COL mRNA expression was significantly increased in the low- and high-dose groups (P<0.01). Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN, and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
5.Traditional Chinese Medicine Intervention in Diabetic Nephropathy Based on PI3K/Akt Signaling Pathway: A Review
Miao XU ; Xiaolei JIA ; Lingling QIN ; Haiyan WANG ; You WANG ; Yuzhuo CHANG ; Cuiyan LYU ; Tonghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):90-97
Diabetic nephropathy (DN) is a renal disorder induced by prolonged hyperglycemia, with major pathological features including persistent albuminuria, progressive decline in glomerular filtration rate, and elevated arterial blood pressure. As one of the most common and severe microvascular complications of diabetes, the pathogenesis of DN is complex and multifactorial. Without timely and effective treatment, DN may eventually progress to end-stage renal disease (ESRD). Currently available therapeutic options are often associated with significant adverse effects and high costs, and a large number of patients still progress to ESRD due to delayed treatment. Therefore, there is an urgent need for safer and more effective treatment strategies to improve the living standards and enhance the survival and quality of life of patients with DN. Modern studies have demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway plays a critical role in oxidative stress, inflammatory responses, autophagy, and glycolysis, and is closely associated with the pathophysiological progression of DN. In recent years, traditional Chinese medicine (TCM) has achieved remarkable progress in the prevention and treatment of DN, supported by rich clinical experience and confirmed therapeutic efficacy. With its characteristics of multi-target, multi-component, and multi-pathway actions, along with minimal side effects, TCM can delay the progression of DN and alleviate patient symptoms. Among these mechanisms, the regulation of the PI3K/Akt signaling pathway has gradually become a research hotspot. This paper systematically reviews the role and mechanisms of the PI3K/Akt signaling pathway in the onset and progression of DN based on extensive literature research, summarizes the latest research advances on the precise modulation of the PI3K/Akt pathway by Chinese medicine monomers, active constituents, Chinese patent medicines, and herbal compound formulas in the treatment of DN, aiming to provide a strong theoretical reference for the development of clinically effective agents for DN prevention and treatment.
6.Qualitative study on sustainability of intervention measures in the Shandong Provincial Department′s Joint Salt Reduction Project
Jingsong YANG ; Jing DONG ; Zhenzhong WANG ; Jia LI ; Xiaolei GUO ; Yihao ZHAO ; Xuejun YIN ; Ruitai SHAO
Chinese Journal of Preventive Medicine 2024;58(11):1697-1704
Objective:To employ qualitative research methods to evaluate the sustainability of the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) interventions and their influencing factors.Method:In September 2023, interviewees meeting the inclusion criteria were recruited through purposive sampling in Jinan, Shandong Province. A semi-structured interview guide was designed based on the CFIR and RE-AIM frameworks. Personal in-depth interviews and focus group discussions were conducted to gather insights on the feasibility, effectiveness, and sustainability of the project interventions from various stakeholders, including representatives from the government, food manufacturers, restaurants, academia, and residents.Results:A total of 15 individuals participated in in-depth interviews, involving six representatives from food manufacturers, four from restaurants, three from the government, and two from academia. There were four focus group discussions with 30 residents. The study found that at the individual resident level, health awareness and the availability of sodium reduction tools in the market could affect their salt reduction practices. For food manufacturers and restaurants, consumers′ preferences, technical challenges in reformulation, and government support were key factors determining the smooth progress of their salt reduction efforts. At the governmental level, multi-sectional coordination, chronic disease management demonstration areas, and the impact of the pandemic were the main factors influencing the implementation of sodium reduction interventions.Conclusion:Future endeavours should strengthen long-term management and optimise the complex influencing factors associated with intervention measures. This will be essential in sustaining and expanding the positive health outcomes achieved through the Shandong population sodium reduction strategy.
7.Qualitative study on sustainability of intervention measures in the Shandong Provincial Department′s Joint Salt Reduction Project
Jingsong YANG ; Jing DONG ; Zhenzhong WANG ; Jia LI ; Xiaolei GUO ; Yihao ZHAO ; Xuejun YIN ; Ruitai SHAO
Chinese Journal of Preventive Medicine 2024;58(11):1697-1704
Objective:To employ qualitative research methods to evaluate the sustainability of the Shandong-Ministry of Health Action on Salt and Hypertension (SMASH) interventions and their influencing factors.Method:In September 2023, interviewees meeting the inclusion criteria were recruited through purposive sampling in Jinan, Shandong Province. A semi-structured interview guide was designed based on the CFIR and RE-AIM frameworks. Personal in-depth interviews and focus group discussions were conducted to gather insights on the feasibility, effectiveness, and sustainability of the project interventions from various stakeholders, including representatives from the government, food manufacturers, restaurants, academia, and residents.Results:A total of 15 individuals participated in in-depth interviews, involving six representatives from food manufacturers, four from restaurants, three from the government, and two from academia. There were four focus group discussions with 30 residents. The study found that at the individual resident level, health awareness and the availability of sodium reduction tools in the market could affect their salt reduction practices. For food manufacturers and restaurants, consumers′ preferences, technical challenges in reformulation, and government support were key factors determining the smooth progress of their salt reduction efforts. At the governmental level, multi-sectional coordination, chronic disease management demonstration areas, and the impact of the pandemic were the main factors influencing the implementation of sodium reduction interventions.Conclusion:Future endeavours should strengthen long-term management and optimise the complex influencing factors associated with intervention measures. This will be essential in sustaining and expanding the positive health outcomes achieved through the Shandong population sodium reduction strategy.
8.Establishment and evaluation of two common pressure ulcer rat models
Yi LIU ; Xiaolei LI ; Xinpei LIANG ; Na WANG ; Shan MA ; Xinping ZHANG ; Rufu JIA ; Su ZHANG ; Xian LI
Chinese Journal of Comparative Medicine 2024;34(3):93-101
Objective A comparison of two method of establishing pressure ulcer rat models to determine which is the most suitable for experimental use.Methods 18 male SD rats were randomly divided into control(n=6),model A(n=6)and model B(n=6)groups.In the control group,iodophor treatment was given after hair removal at the simulated modeling site.In model group A,longitudinal compression was performed by simple deep-tissue foreign body implantation.In model group B,transverse compression was performed via the magnet compression method.The times required to complete the process and for each stage of pressure ulcer model establishment in each group were recorded.The general condition of the rats was observed,and the modeling rate,mortality rate,and infection rate were compared.Results By naked eye,we observed that the model A and model B groups gradually developed redness and swelling,ulceration,bleeding,exudation,and necrosis.Comparison of the whole time to produce pressure uler between model A and model B groups:the difference between the two groups was statitically significant(P<0.05).Comparison of the time to produce pressure injury between Model A and Model B:The difference between the two groups at stage Ⅰ was not statistically significant(P>0.05);the difference between the two groups at stage Ⅱ was statistically significant(P<0 05);the difference between the two groups at stage Ⅲ was statistically significant(P<0 05);the difference between the two groups at stage Ⅳ was statistically significant(P<0 05).The mental and sports scores of the rats in the control group were significantly different from those in the model A and model B groups(P<0.05).The general state of rats in the model group A was significantly different from that in the model B group,and coat color was dimer and activity decreased in the model group A.The modelling rate of rats in both model A and model B groups was 100%.The mortality and infection rates of the model group A were higher than those of the model group B,which were 33.34%and 16.70%,respectively.Conclusions Successful preparation of a four-stage model of pressure ulers in both modalities.The two method have both commonalities and distinct characteristics.The magnet compression method required less time,the rats were generally in good condition,and the mortality and infection rates were low;thus it is suitable for short-term intervention research.The simple deep-tissue foreign body implantation method took longer,required rats to have a certain level of tolerance,had high infection and mortality rates,and is more suitable for use for long-term observations of pressure ulcers.
9.Effect of neuromuscular training on femoroacetabular impingement
Yun YANG ; Hongyue ZHANG ; Yaohua ZHANG ; Xiaolei LIU ; Huanxin XIE ; Qiang LI ; Jia LI ; Huaqing YANG
Chinese Journal of Rehabilitation Theory and Practice 2022;28(7):759-763
ObjectiveTo observe the effect of neuromuscular training on femoroacetabular impingement. MethodsFrom January, 2017 to November, 2021, 27 patients with femoroacetabular impingement in Beijing Rehabilitation Hospital were randomly divided into control group (n = 13) and observation group (n = 14). The control group accepted routine rehabilitation training, and the observation group accpeted neuromuscular training in addition. They were assessed with Visual Analogue Scale (VAS) for pain, peak torque (PT) of hip flexion and extension, Y-balance test (YBT) and simplified International Hip Outcome Tool (iHOT-12) before and after treatment. ResultsThe VAS score, PT, YBT score and iHOT-12 score improved in the observation group after treatment (|t| > 3.628, P < 0.01), while the VAS score and PT improved in the control group (|t| > 3.409, P < 0.01). After treatment, the VAS score, PT, YBT score and iHOT-12 score were better in the observation group than in the control group (|t| > 2.067, P < 0.05). ConclusionNeuromuscular training can relieve the pain of patients with femoroacetabular impingement, and improve the muscle strength and function of hip joint.
10.Expert consensus on diagnosis and treatment of severe fever with thrombocytopenia syndrome
Guang CHEN ; Tao CHEN ; Sainan SHU ; Ke MA ; Xiaojing WANG ; Di WU ; Hongwu WANG ; Meifang HAN ; Xiaojuan JIA ; Mingyuan LIU ; Xiaolei LIU ; Yuanyuan LI ; Xianfeng ZHANG ; Jiazhi LIAO ; Feng FANG ; Xiaoping LUO ; Qin NING
Chinese Journal of Clinical Infectious Diseases 2022;15(4):253-263
Since 2010, the incidence of severe fever with thrombocytopenia syndrome (SFTS) has been increased. Owing the progress in diagnosis and treatment, the overall mortality of SFTS in China has decreased, while the mortality in critical SFTS patients is still high. In order to provide guidance and working procedures for clinicians to diagnose and treat critical SFTS, the National Medical Center for Major Public Health Events invited experts to discuss and formulate this consensus based on their experience and up-to-date knowledge on SFTS.

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