Electroacupuncture improves peripheral neuropathy by up-regulating Sirt1/PGC-1α/TFAM pathway in type 2 diabetes rats with peripheral neuropathy. / 基于Sirt1/PGC-1α/TFAM通路探讨电针治疗2åž‹ç³–å°¿ç— å‘¨å›´ç¥žç»ç— å˜çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.

Foreign substance injection for esthetic purposes associated with delayed unilateral sciatic nerve impairment: A surgical case report.

Attempts at body contour modifications have led to the use of different alloplastic materials that can irreversibly damage health and risk patients' lives. These modeling substances can induce a general autoimmune inflammatory response, producing a very heterogeneous clinical spectrum ranging from mild and severe systemic to local symptoms that sometimes affect peripheral nerves. We report a unique case of a tumor-like sciatic nerve impairment produced months after the injection of a modeling substance into the buttocks for esthetic purposes. The patient was treated with a surgical decompression of the sciatic nerve that encompassed the removal of the injected mass. This approach ultimately yielded a complete neurological recovery of the affected nerve. We emphasize the diagnostic approach and surgical management employed in this unique case and review the current literature on this infrequent complication.

Individuals Diagnosed With Type 2 Diabetes Mellitus and the Status of Vitamin B12 Deficiency: A Review.

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder with a multifactorial etiology and a significant global burden. In recent years, emerging evidence has suggested a potential link between T2DM and vitamin B12 deficiency, raising concerns about its impact on disease progression, management, and associated complications. This comprehensive review critically examines the current understanding of the prevalence, risk factors, clinical implications, and management strategies related to vitamin B12 deficiency in individuals diagnosed with T2DM. The review begins by providing an overview of the epidemiology of T2DM and its associated complications, underscoring the need for comprehensive management approaches. Subsequently, it delves into the physiology of vitamin B12, including its sources, absorption mechanisms, and biological functions, laying the groundwork for understanding the potential implications of deficiency in T2DM. A thorough analysis of the literature is conducted to elucidate the prevalence and risk factors of vitamin B12 deficiency in individuals with T2DM, considering factors such as age, duration of diabetes, medication use (e.g., metformin), dietary patterns, and comorbidities. Special attention is given to the role of metformin, the first-line therapy for T2DM, in precipitating or exacerbating vitamin B12 deficiency through mechanisms involving alterations in the gut microbiota and intestinal absorption. The review further explores the clinical manifestations and diagnostic challenges associated with vitamin B12 deficiency in the context of T2DM, emphasizing the importance of recognizing subtle symptoms and implementing appropriate screening protocols. It discusses the potential implications of vitamin B12 deficiency on glycemic control, diabetic neuropathy, cognitive function, cardiovascular health, and overall quality of life in individuals with T2DM. In addressing the management of vitamin B12 deficiency in T2DM, the review examines various therapeutic strategies, including oral and parenteral supplementation, dietary modifications, and lifestyle interventions. It critically evaluates the evidence supporting routine screening for vitamin B12 deficiency in individuals with T2DM and discusses controversies surrounding optimal supplementation protocols, dosing regimens, and monitoring strategies. Furthermore, the review highlights gaps in current knowledge and identifies areas for future research, such as the long-term effects of vitamin B12 supplementation on clinical outcomes in T2DM, the impact of genetic factors on vitamin B12 metabolism, and the potential role of personalized interventions. Overall, this review consolidates existing evidence and provides insights into the complex relationship between T2DM and vitamin B12 deficiency, aiming to inform clinical practice, enhance patient care, and guide future research endeavors in this important area of metabolic medicine.

Efficacy of electro-acupuncture versus sham acupuncture for diabetic peripheral neuropathy: study protocol for a three-armed randomised controlled trial.

INTRODUCTION: Specific treatment for diabetic peripheral neuropathy (DPN) is still lacking, and acupuncture may relieve the symptoms. We intend to investigate the efficacy and safety of electro-acupuncture (EA) in alleviating symptoms associated with DPN in diabetes. METHODS AND ANALYSIS: This multicentre, three-armed, participant- and assessor-blind, randomised, sham-controlled trial will recruit 240 eligible participants from four hospitals in China and will randomly assign (1:1:1) them to EA, sham acupuncture (SA) or usual care (UC) group. Participants in the EA and SA groups willl receive either 24-session EA or SA treatment over 8 weeks, followed by an 8-week follow-up period, while participants in the UC group will be followed up for 16 weeks. The primary outcome of this trial is the change in DPN symptoms from baseline to week 8, as rated by using the Total Symptom Score. The scale assesses four symptoms: pain, burning, paraesthesia and numbness, by evaluating the frequency and severity of each. All results will be analysed with the intention-to-treat population. ETHICS AND DISSEMINATION: The protocol has been approved by the Ethics Committee of the Beijing University of Chinese Medicine (Identifier: 2022BZYLL0509). Every participant will be informed of detailed information about the study before signing informed consent. The results of this trial will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2200061408.

Diabetes in spotlight: current knowledge and perspectives of photobiomodulation utilization.

Introduction: Diabetes is a global health concern characterized by chronic hyperglycemia resulting from insulinopenia and/or insulin resistance. The rising prevalence of diabetes and its associated complications (ulcers, periodontitis, healing of bone defect, neuropathy, retinopathy, cardiopathy and nephropathy) necessitate innovative therapeutic approaches. Photobiomodulation (PBM), involves exposing tissues and cells to low-energy light radiation, leading to biological effects, largely via mitochondrial activation. Methods: This review evaluates preclinical and clinical studies exploring the potential of PBM in diabetes and its complications, as well all clinical trials, both planned and completed, available on ClinicalTrials database. Results: This review highlights the variability in PBM parameters across studies, hindering consensus on optimal protocols. Standardization of treatment parameters and rigorous clinical trials are needed to unlock PBM's full therapeutic potential. 87 clinical trials were identified that investigated PBM in diabetes mellitus (with 5,837 patients planned to be treated with PBM). Clinical trials assessing PBM effects on diabetic neuropathy revealed pain reduction and potential quality of life improvement. Studies focusing on wound healing indicated encouraging results, with PBM enhancing angiogenesis, fibroblast proliferation, and collagen density. PBM's impact on diabetic retinopathy remains inconclusive however, requiring further investigation. In glycemic control, PBM exhibits positive effects on metabolic parameters, including glucose tolerance and insulin resistance. Conclusion: Clinical studies have reported PBM-induced reductions in fasting and postprandial glycemia without an increased hypoglycemic risk. This impact of PBM may be related to its effects on the beta cells and islets in the pancreas. Notwithstanding challenges, PBM emerges as a promising adjunctive therapy for managing diabetic neuropathy, wound healing, and glycemic control. Further investigation into its impact on diabetic retinopathy and muscle recovery is warranted.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

BACKGROUND: Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. METHODS: The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. RESULTS: DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. CONCLUSION: DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Multi-feature, Chinese-Western medicine-integrated prediction model for diabetic peripheral neuropathy based on machine learning and SHAP.

BACKGROUND: Clinical studies have shown that diabetic peripheral neuropathy (DPN) has been on the rise, with most patients presenting with severe and progressive symptoms. Currently, most of the available prediction models for DPN are derived from general clinical information and laboratory indicators. Several Traditional Chinese medicine (TCM) indicators have been utilised to construct prediction models. In this study, we established a novel machine learning-based multi-featured Chinese-Western medicine-integrated prediction model for DPN using clinical features of TCM. MATERIALS AND METHODS: The clinical data of 1581 patients with Type 2 diabetes mellitus (T2DM) treated at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine were collected. The data (including general information, laboratory parameters and TCM features) of 1142 patients with T2DM were selected after data cleaning. After baseline description analysis of the variables, the data were divided into training and validation sets. Four prediction models were established and their performance was evaluated using validation sets. Meanwhile, the accuracy, precision, recall, F1 score and area under the curve (AUC) of ROC were calculated using ten-fold cross-validation to further assess the performance of the models. An explanatory analysis of the results of the DPN prediction model was carried out using the SHAP framework based on machine learning-based prediction models. RESULTS: Of the 1142 patients with T2DM, 681 had a comorbidity of DPN, while 461 did not. There was a significant difference between the two groups in terms of age, cause of disease, systolic pressure, HbA1c, ALT, RBC, Cr, BUN, red blood cells in the urine, glucose in the urine, and protein in the urine (p < 0.05). T2DM patients with a comorbidity of DPN exhibited diverse TCM symptoms, including limb numbness, limb pain, hypodynamia, thirst with desire for drinks, dry mouth and throat, blurred vision, gloomy complexion, and unsmooth pulse, with statistically significant differences (p < 0.05). Our results showed that the proposed multi-featured Chinese-Western medicine-integrated prediction model was superior to conventional models without characteristic TCM indicators. The model showed the best performance (accuracy = 0.8109, precision = 0.8029, recall = 0.9060, F1 score = 0.8511, and AUC = 0.9002). SHAP analysis revealed that the dominant risk factors that caused DPN were TCM symptoms (limb numbness, thirst with desire for drinks, blurred vision), age, cause of disease, and glycosylated haemoglobin. These risk factors were exerted positive effects on the DPN prediction models. CONCLUSIONS: A multi-feature, Chinese-Western medicine-integrated prediction model for DPN was established and validated. The model improves early-stage identification of high-risk groups for DPN in the diagnosis and treatment of T2DM, while also providing informative support for the intelligent management of chronic conditions such as diabetes.

Evidence mapping of traditional Chinese medicine in diabetic peripheral neuropathy treatment.

Objective: Diabetic peripheral neuropathy (DPN) stands as a crucial complication of diabetes, significantly affecting patients' quality of life. This study aims to elucidate the evidence distribution from clinical randomized controlled trials (RCTs) on DPN treatment with traditional Chinese medicine (TCM) through evidence mapping. Methods: A comprehensive search was conducted from January 2017 to October 2022 in databases such as Wanfang (China Online Journals), CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), SinoMed (Chinese Biomedical Literature Database), PubMed, Web of Science, and Cochrane Library. Literature related to the treatment of DPN with TCM was selected. From the 1,229 RCTs identified over the past 6 years, relevant data were extracted. The evidence mapping approach was utilized, and trends in publications, study scales, intervention types, and evaluation indicators were analyzed using descriptive text combined with tables and bubble charts. Results: Research on the treatment of DPN with TCM is extensive. The publication trend remains relatively stable with predominantly smaller sample sizes. The main treatments encompass oral Chinese medicine and traditional external treatments. The most common evaluation indicators are neurophysiological, efficiency rate, symptom signs, neuropathy scores, and traditional Chinese symptoms, with less focus on psychological status and the ankle-brachial index (ABI). Conclusion: Shedding light on contemporary research, this study explores the current RCTs evaluating TCM's efficacy in treating DPN. The findings not only highlight the potential role of TCM in addressing diabetic complications but also underscore areas that could benefit from refined research approaches, expanded intervention methods, and broader assessment criteria. Our observations aim to inform and inspire future research directions and clinical practices concerning TCM's role in managing diabetes-associated complications.

Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong.

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.

Behavior of neuropathy symptom score and neuropathy disability score in patients with and without peripheral diabetic neuropathy: A retrospective cohort study.

BACKGROUND: This study aimed to stablish cut-off of early diagnosis of diabetic polyneuropathy (PDN) based on neuropathy symptom score (NSS) and neuropathy disability score (NDS); to determine the behavior of NDD and NDS in patients with and without PDN; and to verify the association between clinical and demographic variables with both tests. METHODS: This retrospective cohort included 86 patients with diabetes. The NSS and NDS evaluations were collected in medical records in two moments: initial (entry into service) and final (after three years). Individuals were categorized in three groups: G1- PDN in both evaluations (N = 27); G2- PDN only in the final evaluation (N = 16); G3-individuals without PDN (N = 43). A ROC curve was performed to evaluate the sensitivity and specificity of NSS and NDS for PDN diagnosis. ANOVA was used to compare NSS and NDS between groups and evaluations, and multiple regression was performed to find predictors of PDN. RESULTS: The NSS and NDS showed excellent sensitivity and specificity (NDS ≥1.5 and NSS ≥6.5) for PDN diagnosis. There was a significant difference between groups in initial (p = 0.000) and final (p = 0.000) NDS and NSS evaluations. There was an association between peripheral arterial disease (PAD) and increase in NSS (p = 0.024) in G2; and association between loss of protective sensation (LOPS) and increase in NSS in G3 (p < 0.001). CONCLUSION: NSS and NDS tests showed excellent sensitivity and specificity for early PDN diagnosis. Behavior of both tests can differ patients with and without PDN. Furthermore, PAD and LOPS can be a predictor of PDN evolution.

Study on the effect and mechanism of Zhenzhu Tongluo pills in treating diabetic peripheral neuropathy injury.

BACKGROUND: As a traditional Mongolian medicine, Zhenzhu Tongluo pills has played a good neuroprotective function in clinic. However, the key mechanisms by which it works are poorly studied. OBJECTIVES: To study the effect and mechanism of Zhenzhu Tongluo pills in treating diabetic peripheral neuropathy injury. METHODS: Diabetic peripheral neuropathy model was established by injecting STZ into rats. Physiological, behavioral, morphological and functional analyses were used to evaluate that the overall therapeutic effect of rats, ELISA, qRT-PCR, Western blot, immunohistochemical staining, HE staining and TUNEL staining were used to further study the related mechanism. RESULTS: Zhenzhu Tongluo pills can significantly improve the physiological changes, behavioral abnormalities, structural and functional damage in diabetic peripheral neuropathy rats, which may be related to the anti-inflammatory and anti-apoptotic effects that realized by regulating PI3K/AKT, MAPK, NF-κB signaling pathways. CONCLUSIONS: Zhenzhu Tongluo pills has neuroprotective effect, and anti-inflammatory and anti-apoptosis may be the important way of its function.

Vitamin D Deficiency Participates in Depression of Patients with Diabetic Peripheral Neuropathy by Regulating the Expression of Pro-Inflammatory Cytokines.

Objective: Vitamin D deficiency is associated with patients with diabetic peripheral neuropathy (DPN), and low levels of vitamin D are common in patients with depression. Depression is common in DPN patients and the definite pathogenesis remains unclear. This study aimed to determine vitamin D deficiency in the onset of depression in DPN and evaluate the effect of vitamin D supplementation on depression. Methods: A total of 192 patients with DPN were enrolled in this study. Clinical and laboratory information was collected. Chemiluminescent immunoassay was used to measure the level of 25(OH)D. Enzyme-linked immunosorbent assay was employed to measure the concentrations of interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and IL-17A. Subjects with low 25(OH)D received 5000IU vitamin D daily for 12 weeks. Depression scores and levels of 25(OH)D, IL-1ß, TNF-α, and IL-17A were re-evaluated after supplementation. Results: The incidence of vitamin D deficiency and depression was high in DPN patients. Compared with vitamin D sufficient participants, Hamilton Depression Rating Scale (HAMD) scores and the levels of inflammatory markers IL-1ß, TNF-α, and IL-17A were significantly higher in insufficient group (all p<0.05). HAMD score, IL-1ß, TNF-α, and IL-17A were negatively correlated with 25(OH)D (all p<0.05). A linear relationship existed among IL-1ß, TNF-α, IL-17A, and 25(OH)D (p<0.05). HAMD scores, IL-1ß, TNF-α, and IL-17A were all reduced significantly after supplementation of vitamin D (p<0.05). Binary logistic analysis revealed that vitamin D insufficiency was an independent risk factor for depression in patients with DPN. Receiver operating characteristic (ROC) curve analysis showed a high sensitivity (87.20%) of 25(OH)D in discriminating DPN patients with depression. Conclusion: Vitamin D deficiency participated in occurrence of depression in DPN patients and could be mediated, at least in part, by upregulation of pro-inflammatory cytokines. Vitamin D supplementation may be effective in improving depressive symptoms in DPN patients.

Research progress of the effective active ingredients of Astragalus mongholicus in the treatment of diabetic peripheral neuropathy.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent consequences of diabetes, with a high incidence and disability rate. The DPN's pathogenesis is extremely complex and yet to be fully understood. Persistent high glucose metabolism, nerve growth factor deficiency, microvascular disease, oxidative stress, peripheral nerve cell apoptosis, immune factors, and other factors have been implicated in the pathogenesis of DPN. Astragalus mongholicus is a commonly used plant used to treat DPN in clinical settings. Its rich chemical components mainly include Astragalus polysaccharide, Astragalus saponins, Astragalus flavones, etc., which play a vital role in the treatment of DPN. This review aimed to summarize the pathogenesis of DPN and the studies on the mechanism of the effective components of Astragalus mongholicus in treating DPN. This is of great significance for the effective use of Chinese herbal medicine and the promotion of its status and influence on the world.

Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS: Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS: The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION: The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.

Ursolic acid alleviates paclitaxel-induced peripheral neuropathy through PPARγ activation.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) reduces the overall quality of life and leads to interruption of chemotherapy. Ursolic acid, a triterpenoid naturally which presents in fruit peels and in many herbs and spices, can function as a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and has been widely used as an herbal medicine with a wide spectrum of pharmacological activities, including anti-cancer, anti-inflammatory and neuroprotective effect. METHODS: We used a phenotypic drug screening approach to identify ursolic acid as a potential neuroprotective drug in vitro and in vivo and carried out additional biochemical experiments to identify its mechanism of action. RESULTS: Our study demonstrated that ursolic acid reduced neurotoxicity and cell apoptosis induced by pacilitaxel, resulting in an improvement of CIPN. Moreover, we explored the potential mechanisms of ursolic acid on CIPN. As a result, ursolic acid inhibited CHOP (C/EBP Homologous Protein) expression, indicating the endoplasmic reticulum (ER) stress suppression, and regulating CHOP related apoptosis regulator (the Bcl2 family) to reverse pacilitaxel induced apoptosis. Moreover, we showed that the therapeutic effect of ursolic acid on the pacilitaxel-induced peripheral neuropathy is PPARγ dependent. CONCLUSIONS: Taken together, the present study suggests ursolic acid has potential as a new PPARγ agonist targeting ER stress-related apoptotic pathways to ameliorate pacilitaxel-induced peripheral neuropathic pain and nerve injury, providing new clinical therapeutic method for CIPN.

Therapeutic Interventions to Improve Static Balance in Type 2 DiabetesMellitus: A Systematic Review and Meta-Analysis.

INTRODUCTION: Diabetes mellitus (DM) is a metabolic disorder characterized by an abnormal increase in blood glucose levels resulting from insulin secretion and/or dysfunctional activity that can lead to several serious complications in addition to decreased postural balance. OBJECTIVE: This study aimed to identify and analyze the main interventions used to improve static balance in patients with DM. METHODS: For the selection of articles, a bibliographic search was performed using PubMed, Scopus, Web of Science, Embase, and Cochrane databases. Only clinical trials that investigated the effect of training on static balance in adults with type 2 DM were selected, and 34 studies were included. RESULTS: The search resulted in the identification of 2681 articles, and of these, 31 were eligible for the study. The identified interventions were proprioceptive, aerobic, resistance training on platforms, in virtual reality, and Tai Chi. The main results obtained were an increase in time in the one-leg stance, Romberg test, and tandem position, a significant increase in the Berg Balance Scale score and balance index, and a reduction in the variables of postural sway. CONCLUSION: There are a variety of effective training methods for improving static balance, and the choice of intervention to be applied goes beyond proven effectiveness, depending on reproducibility and/or financial cost.

Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology.

Background: Xuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic. Purpose: The primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN. Study design and Methods: The active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN. Results: The study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets. Conclusion: In summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.

Mobile Mindfulness Meditation for Cancer-Related Anxiety and Neuropathy: Protocol for a Randomized Controlled Trial.

BACKGROUND: Anxiety- and cancer-related neuropathy are two persistent effects related to treatment for cancer. Mindfulness meditation has been used with substantial impact as a nonpharmacologic intervention to mitigate side and late effects of treatment. Mobile apps are ubiquitous for most of the general population, yet have a particular relevance for cancer survivors, given that physical and geographic limitations can be present. OBJECTIVE: This study aims to describe an ongoing trial of the Mindfulness Coach mobile app for cancer survivors. METHODS: In this randomized waitlist controlled trial, cancer survivors experiencing anxiety- or cancer-related neuropathy (200 for neuropathy and 200 for anxiety) and who had finished primary cancer treatment were invited to participate. Data were collected at 3 time points regardless of randomization condition: baseline, 8 weeks, and 16 weeks. Both face-to-face and web-based recruitment strategies were used. The trial was opened for 2 separate primary outcomes (anxiety- or cancer-related neuropathy). The goal was not to compare these groups but to compare treatment and waitlist groups for each condition. In addition to evaluating the impact of mobile mindfulness on reported anxiety- or cancer-related neuropathy, other pain, fatigue, trauma, sleep, and satisfaction with the Mindfulness Coach app will also be assessed. RESULTS: Outcomes of the study are expected in early 2024. CONCLUSIONS: Mindfulness meditation has become widely practiced, and the use of mobile technology has become ubiquitous. Finding ways to deliver mindfulness meditation to people who have been treated for cancer allows for the intervention to be accessible to a larger number of survivors. The results of this intervention could have implications for further understanding the impact of mindfulness meditation on 2 persistent side and late effects of treatment of cancer, namely anxiety- and cancer-related neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT03581357; https://ClinicalTrials.gov/study/NCT03581357. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/47745.

Electroacupuncture efficacy in diabetic polyneuropathy: Study protocol for a double-blinded randomized controlled multicenter clinical trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is the most common complication of type 2 diabetes mellitus (T2DM); its diagnosis and treatment are based on symptomatic improvement. However, as pharmacological therapy causes multiple adverse effects, the implementation of acupunctural techniques, such as electroacupuncture (EA) has been suggested as an alternative treatment. Nonetheless, there is a lack of scientific evidence, and its mechanisms are still unclear. We present the design and methodology of a new clinical randomized trial, that investigates the effectiveness of EA for the treatment of DPN. METHODS: This study is a four-armed, randomized, controlled, multicenter clinical trial (20-week intervention period, plus 12 weeks of follow-up after concluding intervention). A total of 48 T2DM patients with clinical signs and symptoms of DPN; and electrophysiological signs in the Nerve Conduction Study (NCS); will be treated by acupuncture specialists in outpatient units in Mexico City. Patients will be randomized in a 1:1 ratio to one of the following four groups: (a) short fibre DPN with EA, (b) short fibre DPN with sham EA, (c) axonal DPN with EA and (d) axonal DPN with sham EA treatment. The intervention will consist of 32 sessions, 20 min each, per patient over two cycles of intervention of 8 weeks each and a mid-term rest period of 4 weeks. The primary outcome will be NCS parameters, and secondary outcomes will include DPN-related symptoms and pain by Michigan Neuropathy Screening Instrument (MNSI), Michigan Diabetic Neuropathy Score (MDNS), Dolour Neuropatique Score (DN-4), Semmes-Westein monofilament, Numerical Rating Scale (NRS) for pain assessment, and the 36-item Short Form Health Survey (SF-36). To measure quality of life and improve oxidative stress, the inflammatory response; and genetic expression; will be analysed at the beginning and at the end of treatment. DISCUSSION: This study will be conducted to compare the efficacy of EA versus sham EA combined with conventional diabetic and neuropathic treatments if needed. EA may improve NCS, neuropathic pain and symptoms, oxidative stress, inflammatory response, and genetic expression, and it could be considered a potential coadjutant treatment for the management of DPN with a possible remyelinating effect. TRIAL REGISTRATION: ClinicalTrials.gov. NCT05521737 Registered on 30 August 2022. International Clinical Trials Registry Platform (ICTRP) ISRCTN97391213 Registered on 26 September 2022 [2b].

Effect and Safety of Herbal Medicine Foot Baths in Patients with Diabetic Peripheral Neuropathy: A Multicenter Double-Blind Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of foot baths with Tangbi Waixi Decoction (TW) in treating patients with diabetic peripheral neuropathy (DPN). METHODS: It is a multicenter double-blinded randomized controlled trial. Participants with DPN were recruited between November 18, 2016 and May 30, 2018 from 8 hospitals in China. All patients received basic treatments for glycemic management. Patients received foot baths with TW herbal granules either 66.9 g (intervention group) or 6.69 g (control group) for 30 min once a day for 2 weeks and followed by a 2-week rest, as a therapeutic course. If the Toronto Clinical Scoring System total score (TCSS-TS) ⩾6 points, the patients received a total of 3 therapeutic courses (for 12 weeks) and were followed up for 12 weeks. The primary outcome was change in TCSS-TS score at 12 and 24 weeks. Secondary outcomes included changes in bilateral motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV) of the median and common peroneal nerve. Safety was also assessed. RESULTS: Totally 632 patients were enrolled, and 317 and 315 were randomized to the intervention and control groups, respectively. After the 12-week intervention, patients in both groups showed significant declines in TCSSTS scores, and significant increases in MNCV and SNCV of the median and common peroneal nerves compared with pre-treatment (P<0.05). The reduction of TCSS-TS score at 12 weeks and the increase of SNCV of median nerve at 24 weeks in the control group were greater than those in the intervention group (P<0.05). The number of adverse events did not differ significantly between groups (P>0.05), and no serious adverse event was related with treatment. CONCLUSION: Treatment of TW foot baths was safe and significantly benefitted patients with DPN. A low dose of TW appeared to be more effective than a high dose. (Registry No. ChiCTR-IOR-16009331).