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.

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.

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.

Neuropatia periférica induzida por quimioterápicos: sintomas e o risco de queda em mulheres idosas com câncer / Peripheral neuropathy induced by chemotherapy: symptoms and the risk of falling in elderly women with cancer

Introdução: Os avanços nas áreas da saúde e tecnologia favoreceram o processo de transição demográfica e o aumento da expectativa de vida. Consequentemente, o aumento da população idosa ocasiona um aumento das doenças crônicas não-transmissíveis, que incluem o câncer, considerado a segunda principal causa de morte em todo mundo. Dentre as diversas opções de tratamento do câncer destaca-se a quimioterapia, que durante seu uso o paciente pode apresentar diferentes eventos adversos. Um destes eventos é a neurotoxicidade, conhecida como neuropatia periférica induzida por quimioterápicos (NPIQ), que é caracterizada como uma lesão inflamatória ou degenerativa dos nervos periféricos. Manifesta-se por sintomas sensoriais típicos, como perda de sensibilidade nos membros e perda de reflexos, fraqueza em mãos e pés e disestesias, perda de discriminação entre o toque e temperatura (frio e calor), cujas manifestações clínicas incluem dor, formigamento, choque e queimação, e podem implicar em consequências negativas para a vida cotidiana e tornando-se mais vulnerável a ocorrências de quedas. Objetivos: Avaliar a ocorrência da NPIQ e o risco de queda em mulheres idosas com diagnóstico de câncer. Métodos: Estudo quantitativo, descritivo e transversal, desenvolvido com 60 mulheres idosas que realizavam o tratamento quimioterápico para qualquer tipo de câncer. Os dados coletados foram sócio-demográficos e sobre o câncer, e foram aplicados os instrumentos: Escala de Risco de Queda (Fall Risk Score), Escala de Fragilidade de Edmonton (Edmonton Frail Scale) e Ferramenta de Avaliação de Neuropatia Periférica Induzida por Quimioterapia (FANPIQ). Os dados foram digitados no Microsoft Excel, e analisado no Statistical Package for the Social Sciences - SPSS v. 22.0. Foram realizadas análises descritivas com média e desvio padrão, analítica e testes de regressão multivariada. Resultados: A média de idade das participantes foi 69,57 (DP±7,63) anos, 58,3% apresentava hipertensão arterial e 30% diabetes mellitus, 96,7% utilizavam algum tipo de medicação e 75% apresentavam câncer de mama. Quanto ao risco de queda, 36,7% das participantes afirmaram já ter apresentado algum tipo de queda nos últimos 12 meses, com ou sem lesão; entretanto somente 6,7% apresentaram algum déficit sensorial. Na avaliação da fragilidade, 58,3% das idosas não precisavam de auxílio para realizar atividades básicas da vida diária, e 48,3% das participantes foram aprovadas na cognição. Quanto aos sintomas neuropáticos que avaliou a ocorrência de dormência, formigamento, sensibilidade e neuralgia durante o tratamento quimioterápico, todos com influência em algumas atividades cotidianas das mulheres. De acordo com as análises de regressão, a dormência e formigamento nas mãos, neuralgia, dormência nos pés e sensibilidade ao frio foram itens com associação estatística na escala de fragilidade. Conclusão: Este estudo avaliou a ocorrência da NPIQ e o risco de queda em mulheres idosas com diagnóstico de câncer. Apesar de pouco descrito na literatura, foi possível identificar a influência da NPIQ nas atividades cotidianas, com a associação entre os sintomas e o risco de queda, bem como as limitações funcionais no cotidiano da mulher

Introduction: Advances in the areas of health and technology favored the process of demographic transition and increased life expectancy. Consequently, the increase in the elderly population causes an increase in non-communicable chronic diseases, which include cancer, considered the second leading cause of death worldwide. Among the various cancer treatment options, chemotherapy stands out, as during its use the patient may experience different adverse events. One of these events is neurotoxicity, known as chemotherapy-induced peripheral neuropathy (CIPN), which is characterized as an inflammatory or degenerative lesion of the peripheral nerves. It is manifested by typical sensory symptoms, such as loss of sensitivity in the limbs and loss of reflexes, weakness in the hands and feet and dysesthesias, loss of discrimination between touch and temperature (cold and heat), whose clinical manifestations include pain, tingling, shock and burning, and may result in negative consequences for everyday life and make them more vulnerable to falls. Objective: To assess the occurrence of CIPN and the risk of falling in elderly women diagnosed with cancer. Method: Quantitative, descriptive and cross-sectional study, developed with 60 elderly women who underwent chemotherapy treatment for any type of cancer. The data collected were socio-demographic and about cancer, and the following instruments were applied: Fall Risk Score, Edmonton Frail Scale, and the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool (FANPIQ). Data were entered into Microsoft Excel, and analyzed using the Statistical Package for the Social Sciences - SPSS v. 22.0. Descriptive analyzes were performed with mean and standard deviation, analytical and multivariate regression tests. Results: The participants' mean age was 69.57 (SD±7.63) years, 58.3% had arterial hypertension and 30% had diabetes mellitus, 96.7% used some type of medication and 75% had breast cancer. As for the risk of falling, 36.7% of the participants stated that they had already had some type of fall in the last 12 months, with or without injury; however, only 6.7% had some sensory deficit. In the assessment of frailty, 58.3% of the elderly women did not need help to carry out basic activities of daily living, and 48.3% of the participants passed the cognition test. As for the neuropathic symptoms, it evaluated the occurrence of numbness, tingling, sensitivity and neuralgia during chemotherapy treatment, all of which influenced some of the women's daily activities. According to the regression analyses, numbness and tingling in the hands, neuralgia, numbness in the feet and sensitivity to cold were items with statistical association in the frailty scale. Conclusion: This study evaluated the occurrence of CIPN and the risk of falling in elderly women diagnosed with cancer. Although little described in the literature, it was possible to identify the influence of CIPN on daily activities, with the association between symptoms and the risk of falling, as well as functional limitations in women's daily lives

Neuropathy in multiple sclerosis patients treated with teriflunomide

SUMMARY OBJECTIVE: Teriflunomide is an oral medication approved for the treatment of patients with multiple sclerosis. The primary effect of teriflunomide is to reduce de novo pyrimidine synthesis by inhibiting mitochondrial dihydroorotate dehydrogenase, thereby causing cell-cycle arrest. We aimed to investigate the occurrence of peripheral neuropathy, a rare side effect of teriflunomide, in patients receiving teriflunomide. METHODS: Multiple sclerosis patients receiving teriflunomide (n=42) or other disease modifying therapies (n=18) and healthy controls (n=25) were enrolled in this cross-sectional study between January 2020 and 2021. The mean duration of teriflunomide treatment was 26 months (ranging from 6 to 54 months). All participants underwent neurological examination and nerve conduction studies of tibial, peroneal, sural, superficial peroneal, median, and ulnar nerves by using surface recording bar and bipolar stimulating electrodes. RESULTS: The mean superficial peroneal nerve distal latency and conduction velocity were significantly slower, and the mean superficial peroneal nerve action potential amplitude was lower in patients using teriflunomide (2.50 ms, p<0.001; 47.35 m/s, p=0.030; and 11.05 μV, p<0.001, respectively). The mean peroneal motor nerve distal latency was significantly longer and amplitude was lower in teriflunomide patients (3.68 ms, p<0.001, and 5.25 mV, p=0.009, respectively). During the study period, treatment switching to another disease-modifying therapy was planned in 10 patients, and all neuropathic complaints were reversed after switching. CONCLUSION: Teriflunomide has the potential to cause peripheral neuropathy. The awareness of peripheral neuropathy, questioning the symptoms, and if suspected, evaluation with electromyography and switching the therapy in patients under teriflunomide treatment are crucial.

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.

Clinical characteristics of dry eye in patients with type 2 diabetic peripheral neuropathy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical features of dry eye in patients with type 2 diabetes mellitus complicated with peripheral neuropathy.METHOD: Prospective cohort study. A total of 192 patients with type 2 diabetes were enrolled in the Department of Endocrinology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from July 2021 to March 2022. The right eyes of all patients were selected as the observation eye, among which 122 patients were diagnosed with diabetic peripheral neuropathy(DPN)and 70 patients were diagnosed with non-diabetic peripheral neuropathy(NDPN). The score of ocular surface disease index(OSDI), tear meniscus height, tear meniscus width, corneal epithelial thickness, corneal endothelial cell density, tear secretion test(Schirmer Ⅰ test, SⅠt), corneal sensitivity, meibomian gland function status score, tear film breakup time(BUT), corneal fluorescein sodium staining score and Toronto clinical scoring system(TCSS)score were compared between two groups. The correlation between OSDI score and TCSS score in type 2 diabetes patients was analyzed as well.RESULTS: The morbidity of dry eye in the DPN group(55 eyes, 45.1%)was significantly higher than that of NDPN group(20 eyes, 28.6%; χ2=5.094, P=0.024), BUT and corneal sensitivity score of DPN were lower than NDPN group(P&#x003C;0.001), meanwhile, corneal staining score and meibomian gland function score were higher than NDPN group(P&#x003C;0.001). OSDI scores of all subjects were negatively correlated with TCSS scores(rs=-0.233, P=0.002), and OSDI scores of DPN group were negatively correlated with TCSS scores(rs=-0.511, P&#x003C;0.001), but there was no significant correlation between the two scores of NDPN patients(rs=0.007, P=0.957).CONCLUSIONS: DPN patients are more likely to develop dry eye than NDPN patients. OSDI score is not an accurate evaluation index for type 2 diabetes patients, especially for DPN patients.

Prevention and Treatment of Diabetic Peripheral Neuropathy by Chinese Medicine Through PI3K/Akt Signaling Pathway： A Review / 中国实验方剂学杂志

Diabetic peripheral neuropathy （DPN） is characterized by insidious onset， easy misdiagnosis， and progression to severe consequences such as diabetic foot ulcers， gangrene， and amputation. The main pathological features of DPN are nerve cell injuries， such as axonal degeneration and necrosis， segmental demyelination of nerve fibers， and apoptosis of Schwann cells. The phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway is a classical pathway that communicates intracellular and extracellular information and regulates biological activities such as cell proliferation， differentiation， apoptosis， autophagy， and migration. It widely affects various cells related to DPN. In recent years， numerous studies have found that the sustained high glucose environment causes abnormalities in the PI3K/Akt signaling pathway. This， in turn， accelerates the occurrence and development of DPN by participating in the pathogenesis of DPN， such as glucose and lipid metabolism， oxidative stress， inflammation， autophagy， apoptosis， and angiogenesis. Therefore， regulating the PI3K/Akt signaling pathway is crucial for the treatment of DPN. Currently， there is a lack of effective measures to slow down or reverse DPN in clinical practice. Traditional Chinese medicine （TCM） has unique advantages in preventing and treating DPN with multiple targets， effects， and components. A large number of animal and clinical studies of TCM treatment of DPN have shown that the PI3K/Akt signaling pathway is an important target for TCM treatment of DPN. Regulating the PI3K/Akt signaling pathway can promote myelin sheath repair and regeneration， delay the process of nerve cell death， and play a role in preventing and treating DPN. However， there is currently no systematic review and summary of this field in China and abroad. Therefore， this article summarized the regulation of the PI3K/Akt signaling pathway and its role in the pathogenesis of DPN， as well as the intervention of effective components of single Chinese medicine or compounds on the PI3K/Akt signaling pathway. This study is expected to provide a reference for the clinical diagnosis and treatment of DPN with TCM， basic research， and drug development.

Buyang Huanwutang Treats Diabetic Peripheral Neuropathy via Mitochondrial Transport in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） via mitochondrial transport. MethodDiabetes in SD rats was induced by a high-carbohydrate/high-fat diet and intraperitoneal injection of streptozotocin （STZ）. The 45 diabetic rats were randomly assigned into a DPN group， an alpha-lipoic acid （60 mg·kg-1·d-1） group， and a Buyang Huanwutang （15 g·kg-1·d-1） group， with 15 rats in each group. Fifteen normal SD rats were fed with the standard diet and set as the control group. The rats were administrated with corresponding drugs by gavage for 12 weeks. The paw withdraw threshold （PWT） and motor nerve conduction velocity （MNCV） were measured at the end of medication， and the sciatic nerve and the bilateral dorsal root ganglia of L4-5 were collected. The injury model of NSC34 cells was established by treating with 50 mmol·L-1 glucose and 250 μmol·L-1 sodium palmitate. The NSC34 cells were then randomly assigned into a blank （10% blank serum） group， a DPN （10% blank serum） group， an apha-lipoic acid （10% apha-lipoic acid-containing serum） group， a Buyang Huanwutang （10% Buyang Huanwutang-containing serum） group， and a Buyang Huanwutang + Compound C （CC） （10% Buyang Huanwutang-containing serum + 10 μmol·L-1 CC） group. The cell intervention lasted for 24 h. The immunofluorescence method， immunohistochemistry， and Western blot were employed to determine the expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， phosphorylated cAMP-response element binding protein （p-CREB）， kinesin family member 5A （KIF5A）， and dynein cytoplasmic 1 intermediate chain 2 （DYNC1I2）. ResultCompared with the control group， the DPN group of rats showed increased fasting blood glucose （P<0.01）， decreased MNCV and PWT （P<0.01）， down-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01）， and up-regulated expression of DYNC1I2 （P<0.01）. Compared with the DPN group， drug intervention groups showed increased MNCV and PWT （P<0.01）， up-regulated expression of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01）， and down-regulated expression of DYNC1I2 （P<0.05， P<0.01）. The Buyang Huanwutang group had higher levels of MNCV and KIF5A （P<0.05） and lower level of DYNC1I2 （P<0.01） than the apha-lipoic acid group. Compared with the blank group， the DPN group of NSC34 cells showed decreased levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） and increased level of DYNC1I2 （P<0.01）. The apha-lipoic acid group and Buyang Huanwutang group had higher levels of KIF5A， p-AMPK/AMPK， and p-CREB/CREB （P<0.05， P<0.01） and lower level of DYNC1I2 （P<0.01） in NSC34 cells than the DPN group. Buyang Huanwutang group had higher KIF5A level （P<0.05） in NSC34 cells than the apha-lipoic acid group. Moreover， the Buyang Huanwutang + CC group had lower levels of KIF5A， DYNC1I2， p-AMPK/AMPK， and p-CREB/CREB （P<0.01） in NSC34 cells than the Buyang Huanwutang group. ConclusionBuyang Huanwutang may regulate mitochondrial anterograde transport via the AMPK/CREB pathway to prevent and treat DPN.

Experimental research progress in traditional Chinese medicine prevention and treatment of diabetic peripheral neuropathy based on autophagy / 中国中药杂志

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.

A case of delayed peripheral neuropathy caused by diquat poisoning / 中华劳动卫生职业病杂志

Diquat is a kind of conductive contact-killing herbicides. The damage of central nervous system is relatively common, but the peripheral neuropathy caused by diquat has not been reported yet. In September 2021, we treated a patient with diquat poisoning. During the hospitalization, the patient was diagnosed with peripheral neuropathy. Therapy for peripheral nerve injury was given on the basis of conventional treatment of poisoning. The patient was discharged after his condition was stable. The follow-up showed that the peripheral neuropathy of patient was better than before. According to the condition of this patient, it is suggested that we should not only protect the function of gastrointestinal tract, liver, kidney, and central nervous system early, but should also pay attention to the damage of peripheral nervous system in clinical work. We should intervene earlier to improve the prognosis of patients.