Advances in influential factor and drug treatment studies for taxane-induced peripheral neuropathy / 中国药房

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

Construction of Knowledge Graph Based on Literature Data by Taking Treatment of Diabetic Peripheral Neuropathy with Traditional Chinese Medicine as An Example / 中国实验方剂学杂志

ObjectiveTo systematically sort out the knowledge framework and conceptual logic relationship of "disease-syndrome-treatment-prescription-medicine" in the existing literature on traditional Chinese medicine（TCM） treatment of diabetic peripheral neuropathy（DPN）， to construct of the knowledge map of TCM treatment of DPN， and to promote the explicitation of the implicit knowledge in the literature on the treatment of DPN with TCM. MethodTaking the literature of China National Knowledge Infrastructure about TCM treatment of DPN as the main data source， TCM-related concepts and entities were constructed by manual citation， and the corresponding relationships between the entities were established. Structured data were formed by processing with Python 3.7， and the knowledge graph was constructed based on Neo4j 3.5.34 graph database. ResultThe resulting knowledge graph with TCM diagnosis and treatment logic， defined 12 node labels such as prescriptions， Chinese medicines and syndrome types at the schema layer， as well as 4 types of relationships， such as inclusion， correspondence， selection and composition. It could support the query and discovery of nodes（syndrome elements， syndrome types and treatment methods）， as well as the relationship between each node. ConclusionBased on the literature data， this study constructed a knowledge map for TCM treatment of DPN， which brought together various methods of TCM treatment of DPN， including internal and external treatment. The whole chain knowledge structure of syndrome differentiation and classification for DPN treatment is formed from syndrome element analysis， syndrome type composition to treatment method selection， which can provide new ideas and methods for literature data to serve clinical and scientific research work， as well as reference for visualization of TCM literature knowledge， intellectualization of TCM knowledge services and the standardization of TCM diagnosis and treatment.

Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg-1·d-1） and lipoic acid group （0.026 8 g·kg-1·d-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

Association of serum magnesium and distal symmetric peripheral neuropathy among Filipino patients with Type 2 Diabetes Mellitus

Objective@#This study aims to determine the association of serum magnesium with distal symmetric peripheral neuropathy among persons with type 2 diabetes mellitus (DM).@*Methodology@#A cross-sectional analytical study among adult Filipinos with Type 2 DM. Logistic regression was used to determine the association of serum magnesium with DSPN diagnosed by the Michigan Neuropathy Screening Instrument. The null hypothesis was rejected at 0.05α-level of significance.@*Results@#The average serum magnesium levels were similar between those with versus without DSPN (2.06 ± 0.32 vs 2.05 ± 0.23, p = 0.873); the same was seen for corrected magnesium. There is insufficient evidence to demonstrate a significant statistical difference between those with and without DSPN in relation to glycemic control (HbA1c and FBS). Likewise, there is no significant statistical correlation between serum magnesium levels with HbA1c, FBS, BMI, or duration of diabetes.@*Conclusion@#This present study could not demonstrate any association between DSPN and serum magnesium, even after adjusting for age, sex, and comorbidity.

Impacts of andrographolide on sciatic nerve function damage in diabetic peripheral neuropathy rats by regulating HMGB1/RAGE signaling pathway / 中国药房

OBJECTIVE To investigate the impacts of andrographolide on sciatic nerve function injury in diabetic peripheral neuropathy （DPN） rats by regulating high-mobility group protein box 1 （HMGB1）/receptor for advanced glycation end products （RAGE） signal pathway. METHODS A total of 84 rats were randomly divided into the control group （normal saline）， DPN group （normal saline）， low-dose andrographolide group （0.833 mg/kg）， high-dose andrographolide group （3.332 mg/kg）， lipoic acid group （positive control， 0.1 g/kg）， recombinant rat HMGB1 protein （rHMGB1） group （8 μg/kg）， and high-dose andrographolide+ rHMGB1 group， with 12 rats in each group. All rats except those in the control group were fed with high glucose and high fat diet combined with intraperitoneal injections of streptozotocin to establish the DPN rat model. After 24 hours of successful modeling， medication was administered daily for 8 weeks. The changes in fasting blood glucose， mechanical pain threshold， heat pain threshold and sciatic nerve conduction velocity were detected. Pathological changes in the sciatic nerve of rats and the activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） in the sciatic nerve of rats were also detected. Besides， the expressions of HMGB1， RAGE proteins and phosphorylation level of nuclear factor κB p65（NF-κB p65） protein in rat sciatic nerves were found. RESULTS Compared with the control group， the pathological damage of the sciatic nerve of rats in the DPN group was strengthened， the fasting blood glucose， heat pain threshold， MDA content and the 诊治。E-mail：dqiaur@163.com expressions of HMGB1， RAGE proteins and phosphorylation level of NF-κB p65 protein were increased （P＜0.05）， while the mechanical pain threshold， sensory nerve conduction velocity， motor nerve conduction velocity， and SOD activity were decreased/slowed down （P＜0.05）. Compared with the DPN group， the above indexes were significantly potentiated in the andrographolide low- and high-dose groups and lipoic acid group （P＜0.05）， and the corresponding trends in the rHMGB1 group were opposite to those in the above three administration groups （P＜0.05）. Moreover， rHMGB1 attenuated the hypoglycemic effect of high-dose andrographolide on blood glucose and the improvement of oxidative stress injury in the sciatic nerve of DPN rats （P＜0.05）. CONCLUSIONS Andrographolide may reduce blood glucose by inhibiting the HMGB1/RAGE pathway and oxidative stress， thus ameliorating sciatic nerve injury in DPN rats.

Treatment of Traditional Chinese Medicine for Diabetic Peripheral Neuropathy Based on Mitochondrial Quality Control： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy（DPN） is a neurodegenerative disease of diabetes mellitus involving peripheral nervous system damage， which is characterized by axonal degenerative necrosis， Schwann cell apoptosis and demyelination of nerve myelin sheath as the main pathological features， this disease is highly prevalent and is a major cause of disability in diabetic patients. Currently， the pathogenesis of DPN may be related to oxidative stress， inflammatory response， metabolic abnormality， and microcirculation disorder. The treatment of DPN in modern medicine mainly starts from controlling blood glucose， nourishing nerves and improving microcirculation， which can only alleviate the clinical symptoms of patients， and it is difficult to fundamentally improve the pathological damage of peripheral nerves. Mitochondrial quality control refers to the physiological mechanisms that can maintain the morphology and functional homeostasis of mitochondria， including mitochondrial biogenesis， mitochondrial dynamics， mitochondrial oxidative stress and mitochondrial autophagy， and abnormal changes of which may cause damage to peripheral nerves. After reviewing the literature， it was found that traditional Chinese medicine（TCM） can improve the low level of mitochondrial biogenesis in DPN， maintain the balance of mitochondrial dynamics， inhibit mitochondrial oxidative stress and mitochondrial autophagy， and delay apoptosis of Schwann cells and neural axon damage， which has obvious effects on the treatment of DPN. With the deepening of research， mitochondrial quality control may become one of the potential targets for the research of new anti-DPN drugs， therefore， this paper summarized the research progress of TCM in treating DPN based on four aspects of mitochondrial quality control， with the aim of providing a theoretical research basis for the discovery of new drugs.

A study on the effect of duration of Type 2 diabetes mellitus on nerve conduction velocity and amplitude

Background: Diabetic peripheral neuropathy (DPN) is a frequent complication of diabetes mellitus and a common cause of foot ulcers and non-traumatic lower limb amputations. The duration of diabetes increases the likelihood of developing DPN, and many individuals have subclinical neuropathy without any symptoms. Electrophysiological assessment of nerve conduction is a simple, objective, and easily reproducible technique to detect DPN and to assess its progression with diabetes duration. Aims and Objectives: This study was done to determine the effect of Type 2 diabetes duration on nerve conduction velocity and amplitude. Materials and Methods: A total of 40 patients with Type 2 diabetes were chosen for the study. The subjects were divided into two groups: Group 1 with diabetes duration <7 years, and Group 2 with diabetes duration more than 7 years. The nerve conduction study is done using RMS EMG Medicare systems in the right median nerve (motor component) in both groups of subjects. Results: There was a significant reduction (P = 0.05) in both nerve conduction velocity (48.53 ± 4.95 m/s) and amplitude (3.33 ± 1.15 mv) in diabetic patients with diabetes duration >7 years when compared with nerve conduction velocity (51.69 ± 4.64 m/s) and amplitude (4.05 ± 0.92 mv) in diabetic patients with diabetes duration <7 years. Conclusion: With increase in duration of diabetes, there is a reduction in a nerve conduction velocity and amplitude.

Prevalencia de Neuropatía periférica de pequeñas fibras asociada a retinopatía en diabéticos tipo 2: Uso prueba biomédica por imagen termográfica

Introducción: La neuropatía periférica diabética de fibras delgadas (NPD-fd) son diagnosticadas por pruebas biomédicas vasomotoras cuyo fundamento es la alteración de la termorregulación de la piel. Objetivos: Calcular la prevalencia y los factores asociados a NPD-fd usando imagen termográfica (IT). Métodos: Se realizó un estudio observacional, transversal analítico en una unidad especializada en el ámbito de la atención primaria, en el que se avaluó pacientes con diabetes mellitus tipo 2 mediante pruebas neurológicas periféricas como la sensibilidad táctil y vibratoria para el diagnóstico de NPD de fibras gruesas (NPDfg) y la termorregulación pasiva por IT para la NPD-fd . Ésta última se realizó en la planta del pie utilizando una cámara termográfica en la consulta ambulatoria, evaluando 5 mediciones termográficas plantares por sujeto. Luego, la asociación entre diabéticos con y sin NPD-fd fue analizada respecto a género, edad, tiempo de enfermedad diabética, tipo de tratamiento diabético, hipertensión, retinopatía, nefropatía, dieta baja en carbohidratos, actividad física, síntoma dolor y IMC. Resultados: Se estudiaron 304 pacientes con diabetes mellitus tipo 2, una edad promedio de 65.07±11.39 años, en su mayoría de sexo masculino, encontrándose una NPD-fg en 14.8 %, NPD-fd en 27.3 % y ambas NPD en 34.9%. La asociación de la NPD-fd fue únicamente con el factor de la presencia de retinopatía (α=0,02, C= 0.18). Conclusiones: Se encontró una alta prevalencia de NPD-fd usando una imagen termográfica que estuvo asociado a la presencia de retinopatía.

Introduction: Small fibers diabetic peripheral neuropathy (DPN-sf) are diagnosed by biomedical vasomotor tests whose foundation is altered skin thermoregulation. Objectives: To estimate the prevalence and factors associated with DPN-sf using thermographic imaging (TI). Methods: An observational, cross-sectional, analytical study was performed in a specialized unit in the primary care setting, in which patients with type 2 diabetes mellitus were assessed by peripheral neurological tests such as tactile and vibratory sensitivity for the diagnosis of large fibers peripheral neuropathy (DPN-lf) and passive thermoregulation by TI for DPN-sf .The latter was performed on the sole using a thermographic camera in the outpatient clinic, evaluating 5 plantar thermographic measurements per subject. Then, the association between diabetics with and without DPN-sf was analyzed concerning gender, age, time of diabetic disease, type of diabetic treatment, hypertension, retinopathy, nephropathy, low carbohydrate diet, physical activity, pain symptom, and BMI. Results: 304 patients with type 2 diabetes mellitus were studied, mean age of 65.07±11.39 years, mostly male, finding DPN-lf in 14.8 %, DPN-sf in 27.3 %, and both NPD in 34.9%. The association of DPN-sf was only with the factor of the presence of retinopathy (α=0.02, C= 0.18). Conclusions: We found a high prevalence of DPN-sf using thermographic imaging that was associated with the presence of retinopathy.

Guillain-Barré syndrome / 中华神经科杂志

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots, which is usually triggered by infections. It is characterized by rapidly progressive, symmetrical weakness of the extremities. Some patients develop respiratory insufficiency and many show signs of autonomic dysfunction. Diagnosis can usually be made on clinical grounds, but lumbar puncture and electrophysiological studies can help to substantiate the diagnosis and to differentiate demyelinating from axonal subtypes of GBS. Molecular mimicry of pathogen-borne antigens, leading to generation of crossreactive antibodies that also target gangliosides, is generally accepted pathogenesis of GBS. The treatment of GBS is intravenous immunoglobulin or plasma exchange with general clinical treatment. Most patients have a good prognosis and basically recover within weeks to months. A few patients have persistent neurological dysfunction or even death.

Vasculitic neuropathies / 中华神经科杂志

Vasculitic neuropathies occur when inflammatory cells infiltrate the vessels of peripheral nerves. Patients with vasculitic neuropathies typically present with multiple mononeuropathies (also known as multifocal neuropathy), characterized by the acute-to-subacute onset of painful sensory and motor deficits. Vasculitic neuropathies could develop in the setting of systemic vasculitis. It also could present as a non-systemic vasculitis without other organs involvement. Peripheral nerve biopsy has an important role in the diagnosis of vasculitic neuropathies. In this review, the classification, clinical and electrophysiological manifestations, diagnosis, treatment, and prognosis of vasculitic neuropathies are summarized, with a focus on recent progresses in these areas.

Drug-induced peripheral neuropathy / 中华神经科杂志

There are many causes of peripheral neuropathy, one of which is that caused by various therapeutic drugs, namely drug-induced peripheral neuropathy (DIPN). With the increasing number of cancer patients, chemotherapy-induced peripheral neuropathy (CIPN) is prominent. Most of DIPN showed chronic, sensory and axonal polyneuropathy, and numbness and neuropathic pain were the main symptoms. The medical history of drug exposure and related risk factors are the key to clinical diagnosis. DIPN caused by non-chemotherapy drugs must be stopped in time to prevent further dysfunction. For CIPN, no agents are recommended for the prevention; the appropriateness of dose delaying and reduction, substitutions or stopping chemotherapy should be evaluated; duloxetine is the only agent that has appropriate evidence to support its use, whereas the amount of benefit is limited. It is urgent to perform the multidisciplinary randomized clinical trial for the treatment of CIPN.

A visual analysis of the CiteSpace-based study of diabetic peripheral neuropathy care in China / 中国实用护理杂志

Objective:To analyze the hotspots and frontiers of diabetic peripheral neuropathy nursing research in the past decade in China, and to provide nursing staff with a reference basis for understanding and grasping the direction of research.Methods:The literature related to diabetic peripheral neuropathy nursing from January 1, 2012 to December 31, 2021 was searched through China Journal Full Text Database, China Biomedical Literature Database, CQVIP, and Wanfang, and visualized and analyzed by using CiteSpace software.Results:A total of 763 articles were included in the literature, and the number of articles was analyzed to show a significant upward trend in 2018-2021, with the most articles by authors being 4 each by Liu Dan and An Caixia, and the most articles by institutions being 6 and 5 by Nanjing Chinese Medicine Hospital and Shanghai Jiading District Chinese Medicine Hospital, respectively, with research hotspots being complications related to diabetic peripheral neuropathy, rehabilitation care, and special Chinese medicine care techniques, and research frontiers being quality of life and neurological function.Conclusions:The research base of diabetic peripheral neuropathy is weak, and researchers should focus on the frontiers of international research hotspots in diabetic peripheral neuropathy care to help nursing research produce prospective, high-impact research results and improve patient clinical outcomes.

Effect of epalrestat combined with calcium dobesilate on diabetes peripheral neuropathy and oxidative stress / 中华内分泌外科杂志

Objective:To explore the effect of epalrestat combined with calcium dobesilate on cardiovascular and cerebrovascular diseases and oxidative stress in diabetes patients with peripheral neuropathy.Methods:In a retrospective analysis, 92 patients with diabetic peripheral neuropathy were admitted to the Department of Endocrinology and Metabolism Hospital of Bozhou People’s Hospital from Jun. 2018 to Jun. 2021, which were divided into observation group and control group according to the different treatment methods, with 46 cases in each group. The control group were treated with epalrestat. On this basis, the observation group were given calcium dobesilate combined treatment. The two groups were compared in terms of the Michigan diabetes neuropathy score (MDNS) Michigan neuropathy screening instrument (MNSI) score, oxidative stress reaction [serum superoxide dismutase (SOD), reduced glutathione (GSH) ], clinical efficacy, complications and adverse reactions Using t-test and chi square test.Result:After treatment, the MDNS and MNSI scores of both groups decreased, and the observation group [ (23.49±3.73), (8.49±1.97) ] were lower than the control group [ (28.49±3.85), (11.53±2.28) ] ( t=8.337, 6.843, P<0.05) ; After treatment, the levels of SOD and GSH in both groups increased compared to those before treatment, and the observation group [ (38.96±4.89), (89.79±6.92) ] were higher than the control group those [ (36.42±4.61), (86.74±6.20) ] ( t=2.563, 2.226, P=0.012, 0.028) ; The clinical efficacy of the observation group was higher than that of the control group ( Z=1.592, P=0.042) ; The incidence of complications in the observation group after 1 year was significantly lower than that in the control group ( χ2=4.389, P=0.036) ; The incidence of adverse reactions in the observation group was slightly lower than that in the control group ( χ2=0.155, P=0.694) . Conclusion:Epalrestat combined with calcium dobesilate is effective in the treatment of diabetes peripheral neuropathy, can effectively reduce complications, and has high treatment safety, which is worthy of clinical application.

A cohort study of vincristine-induced peripheral neuropathy in children / 中国当代儿科杂志

OBJECTIVES@#To study the characteristics of vincristine-induced peripheral neuropathy (VIPN) in children with acute lymphoblastic leukemia (ALL) and the factors influencing the development of VIPN.@*METHODS@#The children with ALL, aged 1-18 years, who were treated with CCCG-ALL2015 or CCCG-ALL2020 regimen in the Affiliated Hospital of Guizhou Medical University from January 2018 to February 2022 were enrolled as subjects. According to the influence of age on risk, the children were divided into 1-10 years group with 91 children and >10 years group with 29 children. VIPN was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (5th edition), and the incidence rate, severity, and type of VIPN were compared between different groups.@*RESULTS@#A total of 120 children were enrolled in this study, among whom 56 (46.7%) developed VIPN. The >10 years group had a significantly higher incidence rate of VIPN than the 1-10 years group (69% vs 40%, P<0.05). Among the 56 children with VIPN, 12 (21%) had grade 3 VIPN or above, and 44 (79%) had grade 2 VIPN. There were 77 cases of autonomic nerve symptoms (59.7%), 42 cases of peripheral nerve injury (32.5%), and 10 cases of cranial nerve injury (7.8%). There were no significant differences in the severity and type of VIPN between the groups with different ages, sexes, degrees of risk, or treatment regimens (P>0.05). The results of binary logistic regression analysis showed that age is the influencing factor for the occurrence of VIPN (P>0.05).@*CONCLUSIONS@#There is a relatively high incidence rate of VIPN in children with ALL, with the highest incidence rate of autonomic nervous symptoms. The incidence of VIP in children over 10 years old is relatively high.

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Signaling Pathways Related to Diabetic Peripheral Neuropathy Treated by Chinese Medicine： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is one of the common complications of diabetes. The disease has a long course with nerve pain and other symptoms， seriously affecting the quality of life of patients. DPN is related to high glucose in vivo， inflammation， oxidative stress， apoptosis， and autophagy， involving phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， nuclear factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， and other signaling pathways. At present， the treatment of DPN mainly focuses on symptomatic treatments such as blood glucose control and neurotrophic therapy， but the effect is not ideal. Therefore， it is particularly important to select a reasonable and effective drug to prevent and treat DPN. In recent years， Chinese medicine has played an important role in the treatment of DPN. Many studies have explored the mechanism of Chinese medicine in the treatment of DPN， and it has been found that some Chinese medicine monomers and compounds can regulate signaling pathways to prevent and treat DPN. This paper reviewed the research results of signaling pathways involved in DPN and the regulation of related pathways by Chinese medicine， aiming to provide references for the clinical treatment of DPN.

Role of p38 MAPK Pathway in Diabetic Peripheral Neuropathy and Chinese Medicine Intervention： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is a symptom and/or sign of peripheral nerve dysfunction that occurs in patients with diabetes mellitus when other causes are excluded. DPN， one of the most common complications of diabetes mellitus， can lead to disability， foot ulcers， and amputation at a later stage. Its pathogenesis is closely related to high glucose-induced inflammatory damage， oxidative stress， mitochondrial disorders， and apoptosis in neural tissues. The p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway is a key mechanism mediating the expression of inflammatory factors， oxidative factors， and apoptotic factors of neural tissues in DPN. The inflammatory response， oxidative stress damage， and apoptosis， induced by the activation of p38 MAPK phosphorylation by factors such as high glucose， can cause cell lipid peroxidation， protein modification， and nucleic acid damage， which results in axonal degeneration and demyelination changes. The current treatment of DPN with western medicine has obvious shortcomings such as adverse effects and addictive tendencies. In recent years， the research on traditional Chinese medicine （TCM） in the prevention and treatment of DPN has gradually increased， and the exploration of Chinese medicine intervention in the p38 MAPK pathway transduction to improve DPN has advanced. The present study reviewed the relations of the p38 MAPK pathway with insulin resistance and peripheral neuropathy and summarized the molecular biological mechanisms involved in the pathological process of DPN， such as inflammation regulation， oxidative stress， polyol pathway regulation， and Schwann cell apoptosis in the past 10 years. In addition， the literature on Chinese medicine monomers， Chinese patent medicines， and Chinese medicine compounds in inhibiting inflammatory reactions， oxidative injury， and apoptosis of DPN peripheral nerves based on the p38 MAPK pathway， resisting axonal degeneration and demyelination changes， improving sensory and motor abnormalities， relieving peripheral pain sensitization， and facilitating nerve conduction mechanism to provide references for the development of new drugs for clinical prevention and treatment of DPN.

Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-κB pathway. MethodSD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ， ip） at 35 mg·kg-1 for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK groups， and lipoic acid group （0.026 8 g·kg-1） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4th， 8th， and 12th week of administration. At the 12th week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-κB proteins in the sciatic nerve were measured by Western blot. ResultThe blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （P<0.01）. The levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve in the model group were higher than those in the normal group （P<0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （P<0.01）. Compared with the model group， TBK of the three doses lowered the TWL （P<0.05， P<0.01） and the levels of IL-1β， TNF-α， and NF-κB protein in sciatic nerve of rats （P<0.05， P<0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （P<0.05， P<0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group. ConclusionTBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-κB pathway and inhibits the expression of downstream NF-κB， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1β and TNF-α due to NF-κB activation.

Molecular Mechanism of Tangbikang Granules Against Diabetic Peripheral Neuropathy： Based on Network Pharmacology and Experimental Verification / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Tangbikang granules （TBK） against diabetic peripheral neuropathy （DPN） based on network pharmacology and in-vivo experiment. MethodThe active components in medicinals of TBK and their target genes were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The active components of the medicinals which are not included in TCMSP were searched from previous research. After the analysis of drug-likeness by SwissADME， the target genes of them were predicted with SwissTargetPrediction. DPN-related target genes were retrieved from GeneCards. The common targets of the disease and the prescription were the hub genes of TBK against DPN， which were uploaded to Metascape for Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. High-sugar and high-fat diet and low-dose streptozotocin （STZ， ip） were employed to induce diabetes in rats， and then the model rats were respectively treated with low-dose （0.625 g·kg-1）， medium-dose （1.25 g·kg-1）， and high-dose （2.5 g·kg-1） TBK for 12 weeks. Sensory nerve conduction velocity （SNCV） was evaluated. After hematoxylin and eosin （HE） staining， the sciatic nerve was observed under light microscope to examine the nerve damage. Real-time PCR was performed to detect the gene expression of adenosine monophosphate-activated protein kinase （AMPK） pathway-related targets in rat sciatic nerve， and Western blot to measure the protein expression of AMPK and phosphorylated （p）-AMPK in rat sciatic nerve. ResultThe main active components of TBK， such as quercetin， kaempferol， β-sitosterol， leech pteridine A， stigmasterol， and baicalein were screened out， mainly acting on interleukin-6 （IL-6）， tumor necrosis factor （TNF）， protein kinase B （Akt）， JUN， and HSP90AA1 and signaling pathways such as AMPK， nuclear factor-κB （NF-κB）， and Janus kinase/signal transducer and activator of transcription （JAK/STAT）. Molecular docking results showed that β-sitosterol and stigmasterol had high binding affinity with IL-6， TNF， JUN， and HSP90AA1. As for the animal experiment， compared with the normal group， model group had low SNCV of sciatic nerve （P<0.01）， disordered and loose myelinated nerve fibers with axonotmesis and demyelinization， low mRNA expression of AMPKα， AMPKβ， peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）， Sirtuin 3 （SirT3）， mitochondrial transcription factor A （TFAM）， and low p-AMPK/AMPK ratio in sciatic nerve （P<0.05， P<0.01）. Compared with the model group， TBK of the three doses raised the SNCV （P<0.01）， restored nerve morphology and nerve compactness， and increased the mRNA expression of AMPKα， AMPKβ， PGC-1α， SirT3， and TFAM （P<0.05， P<0.01）. The ratio of p-AMPK/AMPK in the high-dose and medium-dose TBK groups was higher than that in the model group （P<0.01）， while the protein expression in the low-dose TBK group was insignificantly different from that in the model group. ConclusionTBK exerts therapeutic effect on DPN through multiple pathways and targets. The mechanism is that it activates and regulates AMPK/PGC-1α/SirT3 signaling， which lays a basis for further study of TBK in the treatment of DPN.

Chinese Medicine Treats Diabetic Microangiopathy： A Review / 中国实验方剂学杂志

Diabetes and its complications are major public health issues of worldwide concern. Diabetic microangiopathy is a vascular complication of diabetes caused by blood stasis and deficiency， characterized by impaired microcirculation with hyaline deposits. Diabetic nephropathy， diabetic retinopathy， and diabetic neuropathy are the most common types of diabetic microangiopathy， which can be traced back to the pre-diabetes period and is aggravated by the dynamic evolution of diabetes. Therefore， early intervention is required. Anti-oxidative， anti-inflammatory， and microcirculation-improving drugs should be chosen to treat diabetic microangiopathy based on hypoglycemic， lipid-lowering， and hypotensive treatment in clinical practice. Diabetic microangiopathy belongs to the theoretical concept of "collateral disease" in traditional Chinese medicine （TCM）. The core of the treatment of diabetic microangiopathy with Chinese medicine is to protect "tertiary collateral vessels-microvascular"， and Chinese medicines with Qi-replenishing， Yin-nourishing， heat-clearing， and blood-activating effect are used for compatibility in Chinese medicine prescriptions. Based on the understanding and treatment principles of TCM and western medicine for diabetic microangiopathy， this review briefly summarized the research progress of commonly used prescriptions such as Renshen Baihutang， Yuye Tang， Simiao Yongantang， Gegen Qiliantang， Liuwei Dihuangwan， and modern Chinese medicine preparations for the treatment of diabetic microangiopathy. Moreover， the research progress of Chinese medicines including Ginseng Radix et Rhizoma， Astragali Radix， Rehmannia Radix， Lycii Fructus， Notoginseng Radix et Rhizoma， Salviea Miltiorrhizae Radix et Rhizoma， Lonicera Japonica Flos， and Puerariae Lobatae Radix were outlined. This review is expected to provide the clinical basis and theoretical guidance for the treatment of diabetic microangiopathy with Chinese medicine.