BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have...BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.展开更多
Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of dia...Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.展开更多
BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent i...BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent information regulator type 2 homolog-1(SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α(PGC-1α)axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy(T2DPN),potentially breaking this harmful cycle.AIM To validate the effectiveness of electroacupuncture(EA)in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1αaxis.METHODS The effects of EA were evaluated through assessments of metabolic changes,morphological observations,and functional examinations of the sciatic nerve,along with measurements of inflammation and oxidative stress.Proteins related to the SIRT1/PGC-1αaxis,involved in the regulation of mitochondrial biogenesis and antioxidative stress,were detected in the sciatic nerve using Western blotting to explain the underlying mechanism.A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis.RESULTS In addition to diabetes-related metabolic changes,T2DPN rats showed significant reductions in pain threshold after 9 weeks,suggesting abnormal peripheral nerve function.EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats.The SIRT1/PGC-1αaxis,which was downregulated in the model group,was upregulated by EA intervention.The endogenous antioxidant system related to the SIRT1/PGC-1αaxis,previously inhibited in diabetic rats,was reactivated.A similar trend was observed in inflammatory markers.When SIRT1 was inhibited in diabetic rats,these beneficial effects were abolished.CONCLUSION EA can alleviate the symptoms of T2DNP in experimental rats,and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1αaxis.展开更多
Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diab...Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.展开更多
Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,th...Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.展开更多
Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However...Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.展开更多
AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and...AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus;however,other potential causes for PN may be co-existing in patients with diabetes.A prospective cohort study was performed to assess patients with diabetes and PN.We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities,performing clinical(Toronto Clinical Scoring System and the Utah Early Neuropathy Scale),laboratory and electrophysiological assessments in all patients.RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall.However,in patients with type 1 diabetes,presence of a lipid disorder was associated with greater PN severity.In type 2 diabetes patients,both a lipid disorder and cobalamin deficiency were associated with greater PN severity.There was no additive effect upon PN severity with presence of three or more comorbid etiologies.CONCLUSION: The presence of specific,and not general,comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity.展开更多
This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also in...This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also investigated the factors associated with the development of s DPN and compared factors between the sD PN and confirmed DPN(cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference(LSD) analysis or chi-square tests was used to compare parameters among DNP-free, s DPN and c DPN patients. Independent factors associated with s DPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease(DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease(PAD) and coronary artery disease(CAD). Our study suggests that a significant number of T2DM patients are affected by s DPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD.展开更多
The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II...The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB 1 and DQB 1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.展开更多
Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasc...Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasculopathy are main underlying cause of diabetic foot ulcers. Methodology: It was a cross-sectional non-interventional cohort study where all newly diagnosed treatment naïve type 2 diabetic patients were enrolled. Peripheral neuropathy and vasculopathy were detected by Michigan neuropathy screening instrument (MNSI) and ankle brachial index (ABI) respectively. Risk factors for peripheral neuropathy and vasculopathy were determined by univariate and multivariate logistic regression analysis. Statistical significance was considered with P value of Result: Fifty seven patients (37.7%) had early neuropathy with MNSI score of 3.3 ± 0.4. Thirty seven patients (20.6%) had vasculopathy with ABI score of 0.76 ± 0.11. Age (Odd ratio 1.07 (1.02 - 1.11), p 0.003), duration of symptoms (Odd ratio 1.11 95% CI: 1.05 - 1.17, p ≤ 0.001), high HbA1C % (Odd ratio 1.94 95% CI: 1.54 - 2.45, P ≤ 0.001), albumin creatinine ratio (Odd ratio 1.01, 95% CI: 1.00 - 1.01, P ≤ 0.001 ) and cholesterol level (Odd ratio 1.01 95% CI: 1.01 - 1.02, p = 0.001) were found as risk factors for early neuropathy and vasculopathy. Conclusion: Peripheral neuropathy and vasculopathy are frequently reported complications among newly diagnosed treatment naïve patients of type 2 DM. Age, duration of symptoms prior to diagnosis, metabolic parameters like raised HbA1C, hyperlipidemia and spot random albumin creatinine ratio are found to be risk factors for both peripheral neuropathy and vasculopathy.展开更多
Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited availab...Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease progression.The pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not address.Furthermore,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest effect.Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes.In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation.Although previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required.Overall,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.展开更多
The pathogenesis of diabetic peripheral neuropathy(DPN)has not been fully elucidated,and treatment options are limited.Currently,the main strategies for treating DPN are strict glycemic control and symptomatic pain re...The pathogenesis of diabetic peripheral neuropathy(DPN)has not been fully elucidated,and treatment options are limited.Currently,the main strategies for treating DPN are strict glycemic control and symptomatic pain relief.In this editorial,we comment on an article by Li et al,which suggested that modulating the gut microbiota using traditional Chinese medicine(TCM)may be a promising strategy for alleviating DPN symptoms.The regulation of the gut microbiota has received widespread attention in the study of various diseases.TCM can parti-cipate in the regulation of gut microbiota through multiple mechanisms,and this regulatory effect can alleviate the clinical symptoms of DPN.We briefly analyzed the promise of the gut microbiota in the early diagnosis,treatment,and clinical efficacy of TCM for DPN.The gut microbiota has potential value at multiple no-des in the occurrence and progression of DPN.展开更多
BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but...BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.展开更多
Diabetes mellitus (DM) is considered a major public health problem because of its high prevalence and progressive increase of incidence. DM chronic complications are major causes of morbidity and mortality, among whic...Diabetes mellitus (DM) is considered a major public health problem because of its high prevalence and progressive increase of incidence. DM chronic complications are major causes of morbidity and mortality, among which diabetic neuropathy (DN) stands out, affecting 30% - 50% of DM patients. An appropriate medical approach, involving anamnesis and thorough clinical examination, is extremely important for the early diagnosis of DN and, therefore, to the prevention of its complications, including the amputation of limbs. Despite of the importance of DN prevention and treatment, in order to provide improved quality of life and longevity to DM patients, current therapeutic options are very limited with respect to both symptom control and as effective disease therapies. Intensive glucose control is extremely important in order to prevent and avoid the progression of DN, as demonstrated in two large multicenter studies involving patients with type 1 DM, the DCCT (Diabetes Control and Complications Trial) and the EDIC (Epidemiology of Diabetes Interventions and Complications).展开更多
Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulat...Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.展开更多
Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022...Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.展开更多
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are ...BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are causative for hereditary sensory and autonomic neuropathy,which is clinical overlapping with diabetic peripheral neuropathy.Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity.Thus,it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.AIM To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.METHODS By whole-exome sequence analysis of a patient with T2D and his family members,an uncertain variant in SPTLC1 was identified.Bioinformation analysis was used to evaluate the influence of mutation,rare variant gene-level associations for SPTLC1 in T2D,and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724.The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney(HEK)293 cells.RESULTS A single nucleotide variation in SPTLC1(c.1111G>A:p.G371R)was identified in a family with T2D.The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software.This pathogenicity might be derived from the different amino acid properties.In HEK 293T cells,p.G371R of SPTLC1 induced the expression of tumor necrosis factor-αand the percent of apoptosis.Meanwhile,rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D(the overall odds ratio=2.4968,P=0.0164).Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets(P=0.046),and was as sociated with the decreased level of insulin mRNA expression(Spearman r=0.615,P=0.025).CONCLUSION The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.展开更多
Objective: To study the effects of -zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy. Methods: A total of 90 patients with type 2 diabetes...Objective: To study the effects of -zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy. Methods: A total of 90 patients with type 2 diabetes peripheral neuropathy in our hospital from September 2015 to September 2018 were enrolled in this study. The subjects were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group were treated with -zinc sulfate, the treatment group were treated with -zinc sulfate combined with yiqiyangyinghuoxue therapy, the two groups were treated for 3 months. The serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before treatment. After treatment, the serum NSE, UA, Hcy, hs-CRP, HMGB1, CysC, TGF-β1, ESM-1 and plasma ET, TNF of the two groups were significantly lower than before treatment, the serum BDNF, 25-(OH)D3, NO of the two groups were significantly higher than before treatment, and that of the treatment group after treatment were significantly better than the control group. Conclusion: α-zinc sulfate combined with yiqiyangyinghuoxue therapy on patients with type 2 diabetes peripheral neuropathy has a good efficacy, can improve the neuropathy and vascular endothelial damage, improve related factors, and it was worthy clinical application.展开更多
基金National Natural Science Foundation of China,No.82270881 and No.82200928National High-Level Hospital Clinical Research Funding,No.BJ-2023-124 and No.BJ-2023-130.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.
文摘Neuromodulation for diabetic peripheral neuropathy represents a significant area of interest in the management of chronic pain associated with this condition.Diabetic peripheral neuropathy,a common complication of diabetes,is characterized by nerve damage due to high blood sugar levels that lead to symptoms,such as pain,tingling,and numbness,primarily in the hands and feet.The aim of this systematic review was to evaluate the efficacy of neuromodulatory techniques as potential therapeutic interventions for patients with diabetic peripheral neuropathy,while also examining recent developments in this domain.The investigation encompassed an array of neuromodulation methods,including frequency rhythmic electrical modulated systems,dorsal root ganglion stimulation,and spinal cord stimulation.This systematic review suggests that neuromodulatory techniques may be useful in the treatment of diabetic peripheral neuropathy.Understanding the advantages of these treatments will enable physicians and other healthcare providers to offer additional options for patients with symptoms refractory to standard pharmacologic treatments.Through these efforts,we may improve quality of life and increase functional capacity in patients suffering from complications related to diabetic neuropathy.
基金National Natural Science Foundation of China,No.82074532,No.82374577,No.82305375,No.82305376,and No.82405567The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘BACKGROUND Peripheral neuropathy caused by diabetes is closely related to the vicious cycle of oxidative stress and mitochondrial dysfunction resulting from metabolic abnormalities.The effects mediated by the silent information regulator type 2 homolog-1(SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator-1α(PGC-1α)axis present new opportunities for the treatment of type 2 diabetic peripheral neuropathy(T2DPN),potentially breaking this harmful cycle.AIM To validate the effectiveness of electroacupuncture(EA)in the treatment of T2DPN and investigate its potential mechanism based on the SIRT1/PGC-1αaxis.METHODS The effects of EA were evaluated through assessments of metabolic changes,morphological observations,and functional examinations of the sciatic nerve,along with measurements of inflammation and oxidative stress.Proteins related to the SIRT1/PGC-1αaxis,involved in the regulation of mitochondrial biogenesis and antioxidative stress,were detected in the sciatic nerve using Western blotting to explain the underlying mechanism.A counterevidence group was created by injecting a SIRT1 inhibitor during EA intervention to support the hypothesis.RESULTS In addition to diabetes-related metabolic changes,T2DPN rats showed significant reductions in pain threshold after 9 weeks,suggesting abnormal peripheral nerve function.EA treatment partially restored metabolic control and reduced nerve damage in T2DPN rats.The SIRT1/PGC-1αaxis,which was downregulated in the model group,was upregulated by EA intervention.The endogenous antioxidant system related to the SIRT1/PGC-1αaxis,previously inhibited in diabetic rats,was reactivated.A similar trend was observed in inflammatory markers.When SIRT1 was inhibited in diabetic rats,these beneficial effects were abolished.CONCLUSION EA can alleviate the symptoms of T2DNP in experimental rats,and its effects may be related to the mitochondrial biogenesis and endogenous antioxidant system mediated by the SIRT1/PGC-1αaxis.
基金supported by the Projects of the National Key R&D Program of China,Nos.2021YFC2400803(to YO),2021YFC2400801(to YQ)the National Natural Science Foundation of China,Nos.82002290(to YQ),82072452(to YO),82272475(to YO)+5 种基金the Young Elite Scientist Sponsorship Program by Cast,No.YESS20200153(to YQ)the Sino-German Mobility Programme,No.M-0699(to YQ)the Excellent Youth Cultivation Program of Shanghai Sixth People’s Hospital,No.ynyq202201(to YQ)the Shanghai Sailing Program,No.20YF1436000(to YQ)the Medical Engineering Co-Project of University of Shanghai for Science and Technology,10-22-310-520(to YO)a grant from Shanghai Municipal Health Commission,No.202040399(to YO).
文摘Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.
文摘Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82104827 and 82274336)the National High Level Hospital Clinical Research Funding,China(Grant No.:2022-PUMCH-A-265)the Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine(Grant No.:CACM-2022-QNRC2-B14).
文摘Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.
文摘AIM: To analyze a large population of patients with diabetes and peripheral neuropathy(PN) to determine other meaningful comorbid etiologies for PN.METHODS: Peripheral Neuropathy is a common complication of type 1 and 2 diabetes mellitus;however,other potential causes for PN may be co-existing in patients with diabetes.A prospective cohort study was performed to assess patients with diabetes and PN.We compared patients having PN due solely to diabetes with patients possessing co-existing comorbidities,performing clinical(Toronto Clinical Scoring System and the Utah Early Neuropathy Scale),laboratory and electrophysiological assessments in all patients.RESULTS: Patients with either type 1 or 2 diabetes mellitus and co-existing comorbidities did not have more severe clinical or electrophysiological PN phenotypes overall.However,in patients with type 1 diabetes,presence of a lipid disorder was associated with greater PN severity.In type 2 diabetes patients,both a lipid disorder and cobalamin deficiency were associated with greater PN severity.There was no additive effect upon PN severity with presence of three or more comorbid etiologies.CONCLUSION: The presence of specific,and not general,comorbidities in patients with type 1 or 2 diabetes corresponds with greater PN severity.
基金supported by the Scientific Research Grants from the Ministry of Education of China[No.005-383(6-144)]
文摘This study determined the prevalence of diabetic peripheral neuropathy(DPN) and subclinical DPN(s DPN) in patients with type 2 diabetes mellitus(T2DM) using nerve conduction study(NCS) as a diagnostic tool. We also investigated the factors associated with the development of s DPN and compared factors between the sD PN and confirmed DPN(cDPN). This cross-sectional study involved 240 T2DM patients who were successively admitted to the endocrinology wards of Wuhan Union Hospital over the period of January to December 2014. Data on the medical history, physical and laboratory examinations were collected. DPN was diagnosed using NCS. One-way ANOVA with least significant difference(LSD) analysis or chi-square tests was used to compare parameters among DNP-free, s DPN and c DPN patients. Independent factors associated with s DPN were determined using logistic regression. The results showed that 50.8% of the participants had DPN, and among them, 17.1% had sDPN. sDPN showed significant independent associations with age, height, HbA1c, presence of atherosclerosis and diabetic retinopathy. Patients with DPN differed significantly from those without DPN with respect to age, duration of disease(DOD), HbA1c, presence of atherosclerosis, diabetic retinopathy, nephropathy and hypertension. Patients with cDPN, relative to those with sDPN, had significantly longer DOD and higher prevalence of peripheral artery disease(PAD) and coronary artery disease(CAD). Our study suggests that a significant number of T2DM patients are affected by s DPN, and the development of this condition is associated with advanced age, tall stature, poor glycaemic control, presence of diabetic retinopathy and atherosclerosis. On the other hand, patients with cDPN tend to have a longer DOD and are more likely to suffer from PAD and CAD.
基金funded by Vice-chancellor for Research and Technology,Hamadan University of Medical Sciences of Iran,No.9208072467
文摘The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB 1 and DQB 1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients.
文摘Background: The prevalence of diabetes in Pakistan is 11.45%. The reported prevalence of diabetic foot ulceration in Pakistan is between 4% and 10%, with the amputation rate of 8% - 21%. Peripheral neuropathy and vasculopathy are main underlying cause of diabetic foot ulcers. Methodology: It was a cross-sectional non-interventional cohort study where all newly diagnosed treatment naïve type 2 diabetic patients were enrolled. Peripheral neuropathy and vasculopathy were detected by Michigan neuropathy screening instrument (MNSI) and ankle brachial index (ABI) respectively. Risk factors for peripheral neuropathy and vasculopathy were determined by univariate and multivariate logistic regression analysis. Statistical significance was considered with P value of Result: Fifty seven patients (37.7%) had early neuropathy with MNSI score of 3.3 ± 0.4. Thirty seven patients (20.6%) had vasculopathy with ABI score of 0.76 ± 0.11. Age (Odd ratio 1.07 (1.02 - 1.11), p 0.003), duration of symptoms (Odd ratio 1.11 95% CI: 1.05 - 1.17, p ≤ 0.001), high HbA1C % (Odd ratio 1.94 95% CI: 1.54 - 2.45, P ≤ 0.001), albumin creatinine ratio (Odd ratio 1.01, 95% CI: 1.00 - 1.01, P ≤ 0.001 ) and cholesterol level (Odd ratio 1.01 95% CI: 1.01 - 1.02, p = 0.001) were found as risk factors for early neuropathy and vasculopathy. Conclusion: Peripheral neuropathy and vasculopathy are frequently reported complications among newly diagnosed treatment naïve patients of type 2 DM. Age, duration of symptoms prior to diagnosis, metabolic parameters like raised HbA1C, hyperlipidemia and spot random albumin creatinine ratio are found to be risk factors for both peripheral neuropathy and vasculopathy.
文摘Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease progression.The pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not address.Furthermore,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest effect.Acupuncture is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain syndromes.In their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment cessation.Although previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are required.Overall,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.
基金Supported by National Natural Science Foundation of China,No.82104862Scientific Research Project Foundation of Zhejiang Chinese Medical University,No.2023FSYYZZ01 and No.2023RCZXZK49Scientific Research Project Foundation of Zhejiang Association of Rehabilitation Medicine,No.ZKKY2024018.
文摘The pathogenesis of diabetic peripheral neuropathy(DPN)has not been fully elucidated,and treatment options are limited.Currently,the main strategies for treating DPN are strict glycemic control and symptomatic pain relief.In this editorial,we comment on an article by Li et al,which suggested that modulating the gut microbiota using traditional Chinese medicine(TCM)may be a promising strategy for alleviating DPN symptoms.The regulation of the gut microbiota has received widespread attention in the study of various diseases.TCM can parti-cipate in the regulation of gut microbiota through multiple mechanisms,and this regulatory effect can alleviate the clinical symptoms of DPN.We briefly analyzed the promise of the gut microbiota in the early diagnosis,treatment,and clinical efficacy of TCM for DPN.The gut microbiota has potential value at multiple no-des in the occurrence and progression of DPN.
文摘BACKGROUND Diabetic peripheral neuropathy(DPN)is a debilitating complication of diabetes mellitus with limited available treatment options.Radix Salviae,a traditional Chinese herb,has shown promise in treating DPN,but its therapeutic mech-anisms have not been systematically investigated.AIM Radix Salviae(Danshen in pinin),a traditional Chinese medicine(TCM),is widely used to treat DPN in China.However,the mechanism through which Radix Salviae treats DPN remains unclear.Therefore,we aimed to explore the mechanism of action of Radix Salviae against DPN using network pharmacology.METHODS The active ingredients and target genes of Radix Salviae were screened using the TCM pharmacology database and analysis platform.The genes associated with DPN were obtained from the Gene Cards and OMIM databases,a drug-com-position-target-disease network was constructed,and a protein–protein inter-action network was subsequently constructed to screen the main targets.Gene Ontology(GO)functional annotation and pathway enrichment analysis were performed via the Kyoto Encyclopedia of Genes and Genomes(KEGG)using Bioconductor.RESULTS A total of 56 effective components,108 targets and 4581 DPN-related target genes of Radix Salviae were screened.Intervention with Radix Salviae for DPN mainly involved 81 target genes.The top 30 major targets were selected for enrichment analysis of GO and KEGG pathways.CONCLUSION These results suggested that Radix Salviae could treat DPN by regulating the AGE-RAGE signaling pathway and the PI3K-Akt signaling pathway.Therefore,Danshen may affect DPN by regulating inflammation and apoptosis.
文摘Diabetes mellitus (DM) is considered a major public health problem because of its high prevalence and progressive increase of incidence. DM chronic complications are major causes of morbidity and mortality, among which diabetic neuropathy (DN) stands out, affecting 30% - 50% of DM patients. An appropriate medical approach, involving anamnesis and thorough clinical examination, is extremely important for the early diagnosis of DN and, therefore, to the prevention of its complications, including the amputation of limbs. Despite of the importance of DN prevention and treatment, in order to provide improved quality of life and longevity to DM patients, current therapeutic options are very limited with respect to both symptom control and as effective disease therapies. Intensive glucose control is extremely important in order to prevent and avoid the progression of DN, as demonstrated in two large multicenter studies involving patients with type 1 DM, the DCCT (Diabetes Control and Complications Trial) and the EDIC (Epidemiology of Diabetes Interventions and Complications).
基金supported by the National Natural Science Foundation of China,Nos.82271411(to RG),51803072(to WLiu)grants from the Department of Finance of Jilin Province,Nos.2022SCZ25(to RG),2022SCZ10(to WLiu),2021SCZ07(to RG)+2 种基金Jilin Provincial Science and Technology Program,No.YDZJ202201ZYTS038(to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University,No.2022qnpy11(to WLuo)The Project of China-Japan Union Hospital of Jilin University,No.XHQMX20233(to RG)。
文摘Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular mechanisms.Past studies have focused on factors that stimulate axonal outgrowth and myelin regeneration.However,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic injuries.Consequently,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve regeneration.Our current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and inflammation.These actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve injuries.This review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this process.We hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.
文摘Objective:To observe the efficacy of pentoxifylline+thioctic acid in the treatment of patients with painful diabetic peripheral neuropathy(PDPN).Methods:70 patients with PDPN admitted from October 2019 to October 2022 were selected and randomly grouped,with pentoxifylline+thioctic acid treatment in Group A and thioctic acid treatment in Group B,and the treatment efficacy was compared.Results:The treatment efficacy in Group A was higher than that of Group B,P<0.05;the points of each symptom of PDPN in Group A were lower than that of Group B,P<0.05;the C-reactive protein and electromyography indexes of PDPN patients in Group A were better than that of Group B,P<0.05.Conclusion:PDPN patients treated with pentoxifylline+thioctic acid can optimize nerve function,inhibit inflammation progression,and reduce PDPN symptoms,which is an efficient and feasible treatment option.
基金Supported by the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
文摘BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are causative for hereditary sensory and autonomic neuropathy,which is clinical overlapping with diabetic peripheral neuropathy.Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity.Thus,it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.AIM To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.METHODS By whole-exome sequence analysis of a patient with T2D and his family members,an uncertain variant in SPTLC1 was identified.Bioinformation analysis was used to evaluate the influence of mutation,rare variant gene-level associations for SPTLC1 in T2D,and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724.The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney(HEK)293 cells.RESULTS A single nucleotide variation in SPTLC1(c.1111G>A:p.G371R)was identified in a family with T2D.The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software.This pathogenicity might be derived from the different amino acid properties.In HEK 293T cells,p.G371R of SPTLC1 induced the expression of tumor necrosis factor-αand the percent of apoptosis.Meanwhile,rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D(the overall odds ratio=2.4968,P=0.0164).Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets(P=0.046),and was as sociated with the decreased level of insulin mRNA expression(Spearman r=0.615,P=0.025).CONCLUSION The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.
文摘Objective: To study the effects of -zinc sulfate combined with yiqiyangyinghuoxue therapy on related factors in patients with type 2 diabetes peripheral neuropathy. Methods: A total of 90 patients with type 2 diabetes peripheral neuropathy in our hospital from September 2015 to September 2018 were enrolled in this study. The subjects were divided into the control group (n=45) and the treatment group (n=45) randomly. The control group were treated with -zinc sulfate, the treatment group were treated with -zinc sulfate combined with yiqiyangyinghuoxue therapy, the two groups were treated for 3 months. The serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum NSE, UA, Hcy, hs-CRP, BDNF, HMGB1, CysC, TGF-β1, 25-(OH)D3, ESM-1, NO and plasma ET, TNF of the two groups before treatment. After treatment, the serum NSE, UA, Hcy, hs-CRP, HMGB1, CysC, TGF-β1, ESM-1 and plasma ET, TNF of the two groups were significantly lower than before treatment, the serum BDNF, 25-(OH)D3, NO of the two groups were significantly higher than before treatment, and that of the treatment group after treatment were significantly better than the control group. Conclusion: α-zinc sulfate combined with yiqiyangyinghuoxue therapy on patients with type 2 diabetes peripheral neuropathy has a good efficacy, can improve the neuropathy and vascular endothelial damage, improve related factors, and it was worthy clinical application.