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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.
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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.
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Objective To investigate the analgesic effect and mechanism of Buyang Huanwu Decoction on diabetic peripheral neuropathy(DPN)rats.Methods Sixty rats were divided into normal group,model group,low-,medium-and high-dose groups of Chinese medicine,and high-dose + H-89[protein kinase A(PKA)inhibitor]group,with 10 rats in each group.Except for the normal group,rats in all other groups were fed with high-fat and high-sugar chow combined with intraperitoneal injection of streptozotocin(STZ)method to construct DPN model.At the end of drug administration,the foot thermal pain threshold of rats was detected,the motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV)of rats was measured,the intraepidermal nerve fiber(IENF)in the epidermis was observed by immunohistochemistry,and serum fasting insulin(FINS),total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),insulin resistance index(HOMA-IR),and the interleukin(IL)-1β,IL-6,tumor necrosis factor α(TNF-α),vascular endothelial growth factor(VEGF),angiopoietin 1(Ang-1),CD34 levels,cyclic adenosine monophosphate(cAMP)concentration in the sciatic nerve tissues were detected by enzyme-linked immunosorbent assay(ELISA),and Western Blot assay to detect the PKA and the carbohydrate responsive element binding(CREB)in the sciatic nerve tissues.Results Compared with the normal group,foot thermal pain threshold,TC,TG,LDL-C,HOMA-IR,IL-1β,IL-6 and TNF-α levels were significantly increased in the model group(P＜0.05),HDL-C,FINS,VEGF,Ang-1,CD34,IENF,MNCV and SNCV values,cAMP concentration levels,PKA and CREB phosphorylation levels were significantly reduced(P＜0.05).Compared with the model group,the above indexes were significantly improved in the low-,medium-and high-dose groups of Chinese medicine(P＜0.05)in a dose-dependent manner.Compared with the Chinese medicine high-dose + H-89 group,all the indexes were reversed in the Chinese medicine high-dose group.Conclusion Buyang Huanwu Decoction can improve insulin resistance and lipid metabolism,reduce limb pain,improve local microcirculation disorder,and protect nerve function in DPN rats,which reflects the therapeutic characteristics of"activating blood circulation and relieving pain".The pain-relieving effect of Buyang Huanwu Decoction may be related to the improvement of local microcirculation,inhibition of inflammatory factor release and regulation of cAMP/PKA/CREB signaling pathway protein expression.
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BACKGROUND:Persistent hyperglycemia has been identified as promoting neurovascular dysfunction,leading to irreversible endothelial dysfunction,increased neuronal apoptosis,oxidative stress and inflammation.These changes in combination or alone lead to microvascular and macrovascular lesions as well as progressive neuropathy.Noncoding RNAs may provide a new strategy for understanding the etiology,pathogenesis and treatment of the disease. OBJECTIVE:To review the role and mechanism of noncoding RNAs in the occurrence and development of diabetic peripheral neuropathy by reviewing relevant literature at home and abroad,in order to provide new ideas and approaches for noncoding RNAs in the prevention,diagnosis and treatment of diabetes neuropathy. METHODS:CNKI and PubMed were retrieved for relevant literature published from database inception to 2022.The key words were"noncoding RNA;lncRNA;miRNA;diabetes peripheral neuropathy;expression profile"in Chinese and English,respectively.The retrieved documents were summarized and analyzed,and 61 articles were finally selected for further review. RESULTS AND CONCLUSION:(1)Noncoding RNA plays a key role in the pathophysiological process of diabetic peripheral neuropathy.Among the most widely studied regulatory noncoding RNA species,there are long noncoding RNAs,circular RNAs and microRNAs.(2)Through the regulation of noncoding RNAs,the activation or inhibition of related cell pathways,inflammatory genes and downstream-related cytokines will inhibit cell apoptosis,improve inflammation,and thus change the expression of target genes to participate in the process of diabetic neuralgia.(3)Although many microRNAs and long noncoding RNAs have been found to participate in diabetic peripheral neuropathy,the mechanisms of many noncoding RNAs are unclear,and the same noncoding RNAs may play different roles in different modes.Therefore,it is necessary to further study their action modes in disease etiology and pathology,thereby clarifying their role in the pathogenesis of diabetic peripheral neuropathy.However,the criteria for evaluating noncoding RNA activity have not yet been established,and further research is needed on which specific noncoding RNAs play a dominant regulatory role.(4)MicroRNAs,long noncoding RNAs and their target genes can regulate progressive neuropathy,which are expected to become new targets for the clinical prevention and treatment of diabetic peripheral neuropathy and new biomarkers for the development and prognosis of diabetic peripheral neuropathy.
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Objective To observe the effects of Xin-Gui Gel Plaster(Cinnamomi Cortex,Asari Radix et Rhizoma,Euodiae Fructus,Chuanxiong Rhizoma,Borneolum Syntheticum)on peripheral neuropathy in diabetic rats.Methods A single intraperitoneal injection of 1%streptozotonic(STZ,35 mg·kg-1)was used to replicate a type 2 diabetes mellitus(T2DM)rat model followed by the induction of diabetic peripheral neuropathy(DPN)in combination with a long-term(8 consecutive weeks)high-fat and high-sugar diet.SD rats were randomly divided into normal group,model group,Mecobalamin group and Xin-Gui Gel Plaster group,with 6 rats in each group.The rats in the Xin-Gui Gel Plaster group were given Xin-Gui Gel Plaster at acupoints once a day for 8 weeks;the rats in the Mecobalamin group were given Mecobalamin solution by gavage(0.045 mg·kg-1),and the rats in the normal group and the model group were given physiological saline by gavage.Body mass and fasting blood glucose(FBG)were measured at weeks 2,4,6 and 8;the latency of thermal withdrawal latency(TWL)was measured at weeks 4 and 8;nerve conduction velocities,including motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV),were measured at week 8;and serum total cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG)were measured using a fully automated biochemical analyzer.Fasting insulin(FINS)levels were detected by ELISA,and the index of insulin resistance(HOMA-IR)was calculated;and pathological changes in the sciatic nerve tissues of rats were observed by HE staining.Results Compared with the normal group,rats in the model group had significantly lower body mass and FINS levels(P＜0.01),significantly higher levels of FBG,TC,TG and HOMA-IR(P＜0.05,P＜0.01);TWL,MNCV and SNCV were significantly decreased(P＜0.01),and sciatic nerve fibres were disorganized and loosely aligned,with demyelination,axon atrophy and vacuole-like phenomenon.Compared with the model group,there was no significant change in body mass and levels of FBG,TC and TG in the Xin-Gui Gel Plaster group(P＞0.05),FINS level was significantly increased(P＜0.05),and HOMA-IR levels was significantly decreased(P＜0.05);TWL,MNCV and SNCV in the Mecobalamin group and Xin-Gui Gel Plaster group were significantly increased(P＜0.05,P＜0.01),sciatic nerve lesions were improved to different degrees,nerve fibre arrangement was more regular,myelin deficiency and axonal atrophy were significantly improved.Conclusion Xin-Gui Gel Plaster can improve insulin resistance,relieve thermal stimulation sensitivity,improve sciatic nerve conduction velocity to a certain extent in DPN rats,and have a protective effect on peripheral nerves in diabetic rats,but the hypoglycemic and hypolipidemic effects are not obvious.
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ObjectiveTo observe the effect of Buyang Huanwutang in treating diabetic peripheral neuropathy （DPN） by inhibiting pyroptosis through AMP-activated protein kinase （AMPK）/UNC-51-like kinase 1 （ULK1） mitophagy pathway. MethodSixty male SPF SD rats （6-7 weeks old） were used in animal experiments and numbered according to their body mass. They were then randomly divided into four groups by computer： normal group， model group， α-lipoic acid group（60 mg·kg-1）， and Buyang Huanwutang group（15 g·kg-1）， with 15 rats in each group. The diabetic model was established by injection of streptozocin （STZ）. After successful modeling， the α-lipoic acid group and the Buyang Huanwutang group were given corresponding drugs， and the normal group and the model group were given normal saline. Sensory nerve conduction velocity （SNCV） and paw withdrawal threshold （PWT） were measured at the end of administration for 12 weeks. Immunohistochemistry and Western blot were used to detect the expression of phosphorylated AMP activated protein kinase （p-AMPK）， phosphorylated UNC-51-like kinase 1 （p-ULK1）， protein involved in microtubule-associated protein 1 light chain 3 （LC3）， selective autophagy receptors （p62/SQSTM1）， Beclin1， NOD receptor protein structure domain-related proteins 3 （NLRP3）， Caspase-1 （Caspase-1）， and interleukin-1 beta （IL-1β） in dorsal root ganglia （DRG）. Immunofluorescence was used to detect the expression of the N-terminal gasdermin D （N-GSDMD）. ResultCompared with those in the normal group， rats in the model group had increased fasting blood glucose （P<0.01） and significantly reduced SNCV， PWT （P<0.01）， LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 （P<0.01）. In addition， p62， NLRP3， N-GSDMD/GSDMD， IL-1β， and cleaved Caspase-1/Caspase-1 were significantly increased （P<0.01）. Compared with those in the model group， SNCV and PWT were increased （P<0.01） in each administration group， and LC3Ⅱ/LC3Ⅰ， Beclin1， p-AMPK/AMPK， and p-ULK1/ULK1 were significantly increased （P<0.05， P<0.01）. p62， N-GSDMD/GSDMD， cleaved Caspase-1/Caspase-1， NLRP3， and IL-1β decreased （P<0.05， P<0.01）. Compared with the α-lipoic acid group， the Buyang Huanwutang group had significantly increased SNCV， PWT （P<0.05）， LC3Ⅱ/LC3Ⅰ， and p-ULK1/ULK1 （P<0.05） and significantly decreased NLRP3 and N-GSDMD/GSDMD （P<0.05）. ConclusionBuyang Huanwutang regulates mitophagy and inhibits pyroptosis through the AMPK/ULK1 pathway to prevent and treat DPN， and its therapeutic effect may be better than α-lipoic acid.
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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.
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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.
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Diabetic peripheral neuropathy is a common diabetic complication.Presently,our understanding of its pathogenesis is incomplete,and there are no effective treatment options.In-depth research requires the use of animal experiments.The criteria for modeling success and the evaluation method for peripheral nerve function recovery are critical for carrying out animal experiments into type 2 diabetic peripheral neuropathy.However,but there has been a lack of systematic interrogation and analysis of the evaluation method used with type 2 diabetic peripheral neuropathy models.Therefore,the author reviewed the recent data,summarized and analyzed the evaluation method used for animal models of type 2 diabetic peripheral neuropathy of small and large nerve fibers,and proposed future directions for development,providing a reference for related research.
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Objective To explore the correlation between blood uric acid/HDL-C ratio(UHR)and peripheral neuropathy(DPN)in T2DM.Methods A total of 127 T2DM patients admitted to the Endocrinology Department of Wujin Traditional Chinese Medicine Hospital in Changzhou City from August 2022 to August 2023 were selected.They were divided into a simple T2DM group(n=62)and a combined DPN group(DPN,n=65)based on whether or not they had DPN.Compare two groups of general information,biochemical indicators,and UHR.Results Compared with the T2DM group,DPN group DM course of disease,HbA1c,FPG,FIns,HOMA-IR,TG,vibration sensation threshold(VPT),hypersensitive C-reactive protein(hs-CRP),blood uric acid(SUA),and UHR(P＜0.05),HDL-C,tibial nerve motor nerve conduction velocity(mNCV),and superficial peroneal nerve sensory nerve conduction velocity (sNCV)decreased(P＜0. 05). Spearman correlation analysis showed that UHR was positively DM duration of disease,HbA1c,FPG,HOMA?IR,TG,VPT,hs?CRP,and SUA(P＜0. 05),negatively correlated with mNCV,sNCV,and HDL?C(P＜0. 05). Logistic regression analysis showed that UHR,DM duration, hs?CRP,and HbA1c were the influencing factors of DPN. Conclusion Elevated UHR is a influencing factor for the occurrence of DPN in T2DM patients and has good predictive value for DPN.
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Painful diabetic peripheral neuropathy(PDPN)is a chronic complication of diabetes mellitus.The proportion of patients with PDPN is relatively high in China.At present,the latest guidelines recommend a batch of first-line analgesic drugs for PDPN treatment.Many large-scale randomized trials have confirmed the effectiveness of combination therapy.However,the pathological and physiological mechanisms of PDPN are not fully understood.The clinical treatment effect is still not ideal.This article reviews the research progress on the mechanism of PDPN occurrence.
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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.
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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.
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Diabetes Mellitus , Philippinesالملخص
This study aimed to explore the efficacy and safety of Tangmaikang Granules in the treatment of diabetic peripheral neuropathy(DPN). PubMed, Cochrane Library, EMbase, SinoMed, CNKI, Wanfang and VIP were retrieved for randomized controlled trial(RCT) of Tangmaikang Granules in the treatment of DPN. Cochrane handbook 5.3 was used to evaluate the quality of the inclu-ded studies, and RevMan 5.4.1 and Stata 15.1 were employed to analyze data and test heterogeneity. GRADEpro was used to assess the quality of each outcome index. Clinical effective rate was the major outcome index, while the improvement in numbness of hands and feet, pain of extremities, sluggishness or regression of sensation, sensory conduction velocity(SCV) and motor conduction velocity(MCV) of median nerve and peroneal nerve, fasting blood glucose(FBG), 2 h postprandial blood glucose(2hPBG), and glycated hemoglobin(HbA1c) and incidence of adverse reactions were considered as the minor outcome indexes. A total of 19 RCTs with 1 602 patients were eventually included. The Meta-analysis showed that the improvements in clinical effective rate(RR=1.45, 95%CI[1.32, 1.61], P<0.000 01), pain of extremities(RR=1.70, 95%CI[1.27, 2.27], P=0.000 3), MCV of peroneal nerve(MD=4.08, 95%CI[3.29, 4.86], P<0.000 01) and HbA1c(SMD=-1.23, 95%CI[-1.80,-0.66], P<0.000 1) of Tangmaikang Granules alone or in combination in the experimental group were better than those in the control group. Compared with the conditions in the control group, numbness of hands and feet(RR=1.42, 95%CI[1.12, 1.80], P=0.003), sluggishness or regression of sensation(RR=1.41, 95%CI[1.05, 1.91], P=0.02), SCV of median nerve(MD=4.59, 95%CI[0.92, 8.27], P=0.01), SCV of peroneal nerve(MD=4.68, 95%CI[3.76, 5.60], P<0.000 01) and MCV of median nerve(MD=5.58, 95%CI[4.05, 7.11], P<0.000 01) of Tangmaikang Granules in combination in the experimental group were improved by subgroup analysis. The levels of FBG(MD=-0.57, 95%CI[-1.27, 0.12], P=0.11) and 2hPBG(MD=-0.69, 95%CI[-1.70, 0.33], P=0.18) in the experimental group were similar to those in the control group after treatment with Tangmaikang Granules alone or in combination. There was no difference in the safety(RR=1.28, 95%CI[0.58, 2.82], P=0.54) of Tangmaikang Granules in the treatment of DPN between the experimental group and the control group. Tangmaikang Granules could significantly increase clinical effective rate and nerve conduction velocity as well as improve symptoms of peripheral nerve and blood glucose level, and no serious adverse reactions were identified yet. Further validation was needed in future in large-sample, multicenter, high-quality RCTs.
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Humans , Blood Glucose , Diabetic Neuropathies/drug therapy , Drugs, Chinese Herbal/therapeutic use , Glycated Hemoglobin , Hypesthesia/drug therapy , Multicenter Studies as Topic , Pain/etiology , Treatment Outcome , Peripheral Nervous System Diseases/etiologyالملخص
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.
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Objective To systematically retrieve and integrate the clinical randomized controlled trials(RCTs)and systematic reviews/Meta-analyses of traditional Chinese medicine in the treatment of diabetic peripheral neuropathy(DPN)in recent 10 years,aiming to summarize the overall evidence distribution of traditional Chinese medicine in the treatment of DPN.Methods CNKI,WANFANG,VIP,CBM,PubMed,Web of Science,Embase and the Cochrane Library were used as retrieval database.The retrieval time was from January 1,2012 to October 23,2022.RCTs and systematic reviews/Meta-analyses were included.The distribution of evidence was displayed in the form of charts.AMSTAR-1 was used for the methodological quality evaluation of systematic reviews/Meta-analyses.Results A total of 1648 RCTs and 59 systematic reviews/Meta-analyses were included.The overall number of RCTs were on the rise,but most of the scale of the RCTs were relatively small,with 68％of the samples size of a single study concentrated between 50-100;The Duration of intervention was 4-8 weeks;Multi-therapy was the most commonly used intervention,among which the most involved intervention was the combination of TCM decoction;Traditional Chinese medicine monotherapy was mainly oral traditional Chinese medicine decoction.The evaluation indexes of clinical efficacy paid much attention to the total effective rate,nerve conduction velocity,TCM diseases and syndromes;economic index,quality of life,long-term efficacy and other indicators had attracted less attention of researchers.The overall methodological quality of systematic reviews/Meta-analyses was not high,most of which show good clinical efficacy,but lack sufficient evidence support.Conclusion The research results show that the treatment of diabetes peripheral neuropathy with TCM have good characteristics and advantages,the shortcomings are mainly reflected in the low quality of the overall methodology of systematic reviews/Meta-analyses.Suggesting that more high-quality clinical RCTs with breadth and depth are still needed in the future to verify the characteristics and advantages of traditional Chinese medicine in the treatment of diabetic peripheral neuropathy and provide data information support for evidence-based medicine.
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Objective:To investigate the correlation between diabetic peripheral neuropathy(DPN)and the tumor markers in patients with type 2 diabetes(T2DM).Methods:A total of 956 patients with T2DM aged 40 to 70 years were hospitalized in the Department of Endocrinology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2018 to December 2020. There were 347 patients suffered from DPN and 609 patients were not. The differences of serum tumor markers between the two groups were analyzed. We explored the influencing factors independently related to DPN, determined the cutoff points of the tumor markers affecting DPN, and investigated the influencing factors of this tumor marker.Results:The levels of serum carcinoembryonic antigen(CEA), carbohydrate antigen(CA)125, and CA211 were significantly higher in T2DM patients with DPN than those without DPN(all P<0.05). CEA, CA211, age, HbA 1C, and diabetic duration were independent risk factors of DPN. The 2 h postprandial C-peptide was the independent protective factor of the DPN. We found the cutoff points of serum CEA and CA211 when the DPN happened were 2.915 ng/mL and 2.115 ng/mL. When the CEA and CA211 levels were above the cutoff points, the incidence risk of DPN was 1.803(95% CI 1.160-2.802)and 1.741(95% CI 1.150-2.635)times respectively, compared to below cutoff values. Conclusion:Serum CEA, CA125, and CA211 levels were significantly higher in T2DM patients with DPN than those without DPN. CEA and CA211 were independent risk factors of DPN and could potentially serve as markers for screening diabetic microvascular complications of diabetes mellitus.
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[Objective]To investigate the relationship between platelet activation and traditional Chinese medicine(TCM)syndrome distribution in patients with diabetic peripheral neuropathy(DPN).[Methods]A total of 188 DPN patients admitted to our hospital from February 2020 to December 2022 were collected.The TCM syndrome type usesd the index cluster analysis to draw the cluster diagram.The correspondence between TCM syndrome type and lesion degree was analyzed by simple correspondence analysis,and shown on the two-dimensional plan.It compared the general clinical data,platelet parameters and platelet activation of different TCM syndrome types,so as to explore the relationship between platelet activation and the distribution of TCM syndrome types.[Results]The syndrome types summarized in different positions of the cluster map were different.Among them,D-point interception could be divided into five syndrome types:Qi deficiency syndrome,Yin deficiency syndrome,Yang deficiency syndrome,stagnation of blood stasis syndrome and phlegm-dampness blocking collaterals syndrome.Among the 188 DPN patients,phlegm-dampness blocking collaterals syndrome was found in 18 cases(9.57％),stagnation of blood stasis syndrome in 53 cases(28.19％),Yang deficiency syndrome in 28 cases(14.89％),Yin deficiency syndrome in 39 cases(20.74％),and Qi deficiency syndrome in 50 cases(26.60％).The grade of DPN lesion was grade Ⅰ in 56 cases(29.79％),grade Ⅱ in 76 cases(40.43％),and grade Ⅲ in 56 cases(29.79％).The syndrome of phlegm-dampness blocking collaterals and stagnation of blood stasis in the middle of the two-dimensional projection map did not deviate to a certain grade of DPN lesion degree;Yang deficiency syndrome inclined to grade Ⅲ,Yin deficiency syndrome to grade Ⅱ,and Qi deficiency syndrome to grade Ⅰ.Compared with Qi deficiency syndrome,platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW),granular membrane protein-140(GMP-140),platelet activating factor(PAF)and E26 transformation specific-l(ETS-l)in patients with Yin deficiency syndrome and Yang deficiency syndrome were significantly higher(P＜0.05),and PLT,MPV,PDW,GMP-140,PAF and ETS-1 in patients with Yang deficiency syndrome were higher than those of Yin deficiency syndrome(P＜0.05).[Conclusion]DPN can be routinely divided into five basic syndrome types:Qi deficiency,Yin deficiency,Yang deficiency,stagnation of blood stasis and phlegm-dampness blocking collaterals.With the development of DPN,TCM syndromes are transformed from Qi deficiency to Yin deficiency to Yang deficiency,while blood stasis and phlegm-dampness blocking collaterals are accompanied by various stages of DPN patients.In the progress of DPN,platelet activation may be involved in the transformation of TCM syndrome types.
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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.
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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.