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.

Mapping the journey of patients with painful diabetic peripheral neuropathy in the Philippines

Objectives@#Knowing the limited epidemiological studies on painful diabetic peripheral neuropathy (pDPN) in the Philippines, the present review aimed to map the prevalence of pDPN and identify the associated healthcare gaps. @*Materials and Methods@#A systematic search of MEDLINE, Embase and BIOSIS was conducted using predefine inclusion criteria, and relevant studies published in English between 2004 and 2021 were identified. An unstructured literature search was also conducted on public and government websites with no date restriction. Data combined from all sources were synthesized and presented as a simple mean.@*Results@#Three studies were considered for final analyses of the 26 articles retrieved from structured and unstructured searches. The sample sizes for the three studies were 103, 172, and 100, respectively. The simple mean prevalence of pDPN was estimated at 26.5%. Awareness of pDPN based on a published study was 89%. According to published studies, screening and diagnosis of pDPN were 65% and 76.7%, respectively. One-third of the patients with pDPN (75%) were treated. No literature is available for adherence and control.@*Conclusion@#Limited data exist on the different management stages of patients with pDPN in the Philippines. The study analysis will help address the knowledge gaps, improve patient care and pain management, and aid decisionmaking.

Effect of Modified Huangqi Guizhi Wuwutang on Apoptosis-related Bax and Caspase-12 of Sciatic Nerve Cells in Diabetes Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of modified Huangqi Guizhi Wuwutang （MHGW） on the protein and mRNA expression of B-cell lymphoma-2-associated X protein （Bax） and cysteinyl aspartate specific proteinase-12 （Caspase-12） related to the apoptosis of sciatic nerve cells in diabetes rats to explore the mechanism of MHGW in the treatment of peripheral neuropathy in diabetes. MethodAnimal experiments were conducted. A diabetes model was induced in sixty male sprague-dawley （SD） rats by feeding on a high-sugar and high-fat diet combined with streptozotocin （STZ） intraperitoneal injection. Rats with random blood glucose levels ≥ 16.7 mmol·L-1 for three consecutive days were considered to have successfully developed diabetes. Forty-eight rats that successfully developed diabetes were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg-1·d-1）， a high-dose MHGW group （2.5 g·kg-1·d-1）， and a low-dose MHGW group （1.25 g·kg-1·d-1）， with 12 rats in each group. Another 10 rats were assigned to the normal group. Body weight and random blood glucose levels of the rats were monitored. At the end of a 16-week intervention period， the sciatic nerve conduction velocity of the rats was measured using the Key point electromyography collection system. The protein and mRNA expression of Bax and Caspase-12 in the sciatic nerve cells was detected by Western blot analysis and real-time quantitative polymerase chain reaction （Real-time PCR）， respectively. ResultCompared with the normal group， the model group showed a significant decrease in body weight （P<0.01） and a significant increase in random blood glucose levels （P<0.01）. After a 16-week intervention， compared with the model group， the high-dose MHGW group exhibited a significant increase in body weight （P<0.05）， while there were no statistically significant differences in body weight changes among the other treatment groups. Random blood glucose levels significantly decreased in all treatment groups （P<0.01）. After 16 weeks of intervention， compared with the normal group， the model group had significantly reduced motor and sensory nerve conduction velocities （P<0.01）. Compared with the model group， all treatment groups showed significant increases in motor and sensory nerve conduction velocities （P<0.05， P<0.01）. The expression of Bax and Caspase-12 proteins in the sciatic nerve cells was significantly elevated in the model group compared with that in the normal group （P<0.01）. In contrast， all treatment groups showed significant reductions in the expression of Bax and Caspase-12 proteins in the sciatic nerve cells as compared with that in the model group （P<0.01）. The expression of Bax and Caspase-12 mRNA in the sciatic nerve cells significantly increased in the model group compared with that in the normal group （P<0.01）. Compared with the model group， the α-lipoic acid group and the high-dose MHGW group showed significant reductions in the expression of Bax mRNA in the sciatic nerve cells （P<0.05， P<0.01）， while the low-dose MHGW group showed a decreasing trend in the expression of Bax mRNA. The expression of Caspase-12 mRNA in the sciatic nerve cells significantly decreased in all treatment groups （P<0.01）. ConclusionMHGW may improve and repair sciatic nerve damage in diabetes rats by inhibiting sciatic nerve cell apoptosis.

Effect of Modified Huangqi Guizhi Wuwutang on Stress-related IRE1α/CHOP Pathway of Sciatic Nerve Endoplasmic Reticulum in Diabetes Rats / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang （MHGW） on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α （IRE1α） and CCAAT/enhancer-binding protein homologous protein （CHOP）. MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks， followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L-1 were included in study （n=48）. The rats were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg-1·d-1）， a high-dose MHGW group （2.5 g·kg-1·d-1）， and a low-dose MHGW group （1.25 g·kg-1·d-1）. Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks， the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue （LFB） staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species （ROS） levels. Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to evaluate the expression of p-IRE1α protein， IRE1α mRNA， CHOP protein， and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group， the model group showed elevated serum ROS levels （P<0.01）. In contrast， the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group （P<0.01）. The sciatic nerve of the model group showed pathological changes compared with that in the normal group， while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group （P<0.01）. However， the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group （P<0.05， P<0.01）. Furthermore， compared with the normal group， the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve （P<0.01）， while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group （P<0.01）. ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA， thereby preventing and treating peripheral neuropathy in diabetes.

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.

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 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.

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.