Sigma-1 receptor: a new player in neuroprotection against chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy is a very frequent neurological complication in cancer. Oxaliplatin（OXA） is a platinum analogue used as a first-line agent in the treatment of colorectal cancer. OXA induced peripheral neuropathy（OIN） is the main toxicity both during and after the completion of chemotherapy that presents as two distinct syndromes： acute and chronic neuropathy. None of the neuroprotective agents previously tested had prevented or limited the acute and/or chronic OIN. MR309（previously developed as E-52862） is a novel selective sigma-1 receptor（S1R） antagonist with preclinical analgesic activity in OXA-induced neuropathic pain in animal models. This review analyzes the results of the recently published phase Ⅱ, randomized, double-blind, placebo-controlled clinical trial including 124 patients with colorectal cancer（CRC） treated with MR309. This study shows encouraging findings in the setting of neuroprotection against OIN with an acceptable safety profile. The study demonstrated MR309 usefulness in decreasing acute OIN, by reducing cold hypersensitivity experienced by patients, and pointed to the amelioration of chronic OIN by lowering the proportion of patients who developed severe chronic OIN. In addition, we provide a summary and discussion on the pathways that can be modulated by the S1R to explain the observed clinical benefits in the OIN.

Psychosocial adaptation and influencing factors among patients with chemotherapy-induced peripheral neuropathy

BACKGROUND Chemotherapy-induced peripheral neuropathy(CIPN)is a severe and longlasting side effect caused by various anticancer agents that damage sensory,motor and autonomic nerves.It can cause maladaptive behaviors,including disease severity,anxiety,depression,sleep disorders,falls,and social impairment.These disorders have physical,psychological and social effects on patients and can seriously influence their quality of life.AIM To investigate the current situation of psychosocial adaptation to the disease and its influencing factor in patients with CIPN.METHODS A convenience sampling method was used to select 233 patients with CIPN in our hospital from February to August 2021.In addition,a cross-sectional survey was conducted using a sociodemographic questionnaire,the Self-Report Psychosocial Adjustment to Illness Scale,and the European Organisation for the Research and Treatment of Cancer Quality of Life CIPN20(QLQ-CIPN20).Factors influencing psychosocial adaptation in patients with CIPN were analyzed by t-test or one-way analysis of variance,correlation analysis,multiple stepwise regression analysis,and structural equation models.RESULTS The psychosocial adaptation score of patients with CIPN was 52.51±13.18.Multivariate analysis showed that autonomic nerves,tumor stage,motor nerves,education level,availability of caregivers,semi-retirement status,CIPN grade were independent risk factors for patients with CIPN(P<0.05).Structural equation models showed that QLQ-CIPN20 mediated the relationship between CIPN grade,tumor stage,and psychosocial adaptation.CONCLUSION Patients with CIPN have poor psychosocial adaptation and are affected by a variety of physiological,psychological,and social factors.Patients’adaptive responses should be assessed,and targeted interventions implemented.

Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathy via modulation of brain-derived neurotrophic factor expression

OBJECTIVE:Chemotherapeutic agents such as docetaxel(DTX)can trigger chemotherapy-induced peripheral neuropathy(CIPN),which is characterized by unbearable pain.This study was designed to investigate the analgesic effect and related neuronal mechanism of low-frequency median nerve stimulation(LFMNS)on DTX-induced tactile hypersensitivity in mice.METHODS:To produce CIPN,DTX was administered intraperitoneally 4 times,once every 2 d,to male ICR mice.LFMNS was performed on the wrist area,and the pain response was measured using von Frey filaments on both hind paws.Western blot and immunofluorescence staining were performed using dorsal root ganglion and spinal cord samples to measure the expression of brainderived neurotrophic factor(BDNF).RESULTS:Repeated LFMNS significantly attenuated the DTX-induced abnormal sensory response and suppressed the enhanced expression of BDNF in the DRG neurons and spinal dorsal area.CONCLUSIONS:LFMNS might be an effective nonpharmaceutical option for treating patients suffering from CIPN via regulating the expression of peripheral and central BDNF.

Clinical Efficacy of Ultrasonic Medicinal Penetration in the Removal of Blood Stasis and Alleviation of Zhuyu Juanbi Formula in the Treatment of Peripheral Neuropathy Induced by Paclitaxel

Objective: To observe the clinical efficacy and differences of the Zhuyu Juanbi formula delivered through ultrasound at Zusanli on patients with chemotherapy-induced peripheral neuropathy (CIPN) due to paclitaxel injection. Methods: A total of 72 breast cancer patients with CIPN were randomly divided into two groups. The treatment group (36 cases) was treated with oral methylcobalamin plus ultrasonic medicine permeating Zhuyu Juanbi formulae, while the control group (36 cases) was treated with oral methylcobalamin alone. Following two 2 cycles of continuous treatment, the efficacy of peripheral neurotoxicity, TCM syndrome score, FACT/GOG-Ntx score, total neuropathy score, and safety indicators of gynecological cancer patients were observed in the two groups. Result: In the treatment of CIPN, the addition of ultrasonic medicine permeating Zhuyu Juanbi formulae was more effective than oral methylcobalamin alone in reducing peripheral neurotoxicity and improving the quality of life of patients. The difference between the two groups was statistically significant (P < 0.05), and ultrasound drug penetration Zhuyu Juanbi formulae significantly reduced the FACT/ GOG-Ntx score and TNS score in the treatment group. In terms of drug safety, it rarely caused adverse reactions such as grade 3 and 4 leukopenia, and the safety profile was therefore good. Conclusion: The combination of ultrasonic medicine permeating Zhuyu Juanbi formulae and methylcobalamin has been demonstrated to be an effective treatment for peripheral neurotoxicity in patients with PIPN. It has been shown to significantly improve the clinical symptoms of PIPN patients, improve the quality of life of patients, and have a good safety profile.

Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

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.

Clinical efficacy of acupoint injection for chemotherapy-induced peripheral neuropathy of patients with breast cancer

Objective To observe the clinical efficacy of acupoint injection for chemotherapy-induced peripheral neuropathy （ClPN）. Methods Ninety ClPN patients with breast cancer conforming to inclusive criteria were randomly divided into an acupuncture group （group A）, a mecobalamin group （group B） and an acupoint injection group （group C） according to random number table, with 30 cases in each group. In group A, acupuncture was conducted at bilateral Q0chi （I~ LI 11）, H6g6 （~ LI 4）, Z0s^nlT （~__~ ST 36）, S^nyinji^o （^-- ~ SP 6） and Xu^h~i （J~ SP 10）; in group B, intramuscular injection with I mL of mecobalamin injection was conducted; and in group C, acupoint selection was the same as group A, and 0.1 mL of mecobalamin injection was injected into each acupoint, respectively. The treatment was conducted once every three days in each group, and the changes of clinical efficacy, nerve electrophysiology and hemorrheology indicators after treatment for 10 times were observed. Result The total effective rate of group C was 93.1% （27/29）, which was higher than 78.6% （22/28） in group A and 83.3% （25/30） in group B, and the differences among three groups were statistically significant （all P〈0.01）; conduction velocity of lesion nerves was improved in group B and group C, the improvement in group C was obviously superior to the other two groups （all P〈0.01）, hemorrheology indicator was improved in group A and group C （both P〈0.05）. Conclusion The efficacy of acupoint injection with mecobalamin for breast cancer CIPN was significant, which can not only improve the nerve conduction velocity, but also improve the hemorrheology indicator.

A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among individuals.Genetic factor may play an important role in BIPN.Methods:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib therapy.mRNA expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM patients.BIPN is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

Diabetic peripheral neuropathy and neuromodulation techniques:a systematic review of progress and prospects

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.

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.

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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.

Systematic investigation of Radix Salviae for treating diabetic peripheral neuropathy disease based on network Pharmacology

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.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine

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.

Clinical Efficacy of Pentoxifylline Combined with Thioctic Acid in the Treatment of Painful Diabetic Peripheral Neuropathy

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.

Effect of electroacupuncture on chemotherapy-induced peripheral neuropathy in patients with malignant tumor：a single-blinded,randomized controlled trial

OBJECTIVE:To evaluate the effect of electroacupuncture on chemotherapy-induced peripheral neuropathy(CIPN), quality of life and immune status of patients with malignant tumors.METHODS:From Jan, 2013 to May, 2014, 37 patients with malignant tumors were included in this prospective single-blinded study, and randomized to receive either electroacupuncture or acupuncture treatment on basis of chemotherapy.The chemotherapy was continued for 2 courses as previous before the treatments, with 21 days as a course of treatment.Patients received acupuncture and electroacupuncture once per day starting at the day before chemotherapy for consecutive 7 days followed by 14 days off, with 21 days as a course of treatment, and continued for two courses of treatment.Then CIPN, traditional Chinese clinical symptoms,quality of life and immune status were all evaluated for each patient prior treatment and after two courses of treatment.RESULTS:The gender, age, cancer species as well as incidence(83.3% vs 84.2%) and grades of CIPN before treatments were all similar in patients receiving acupuncture or electroacupuncture(all P >0.05).After treatments, most patients with peripheral neuropathy were cured by two courses of electroacupuncture(84.2% vs 21.1%), whereas the other group of patients had similar incidences of peripheral neuropathy compared with prior-acupuncture(83.3% vs 72.2%).Besides, patients receiving electroacupuncture had lower incidence of peripheral neuropathy than those receiving acupuncture treatment(χ~2= 9.745, P = 0.002).The grades of peripheral neuropathy were significantly different in the two groups post-treatment(χ~2= 13.983, P =0.007).The total effective rates for traditional Chinese clinical symptoms were 16.7% and 84.2% in acupuncture and electroacupuncture groups, respectively(Z =-4.239, P < 0.001).The electroacupuncture treatment provided a more satisfactory life for patients compared with acupuncture(Z =-4.76, P < 0.001).Both electroacupuncture and acupuncture had no effects on immune function.CONCLUSION:Electroacupuncture could alleviate CIPN, and improve traditional Chinese clinical symptoms and quality of life, but did not affect immune function.

Mechanism of electroacupuncture on “Zusanli( ST 36) ”for chemotherapy-induced peripheral neuropathy

Objective To observe the effects and duration of electroacupuncture on the mechanical pain threshold induced by paclitaxel and explore its analgesic mechanism.Methods Sixty-four C57BL/6J male mice were randomly divided into 4 groups,a normal+sham EA group,a normal+EA group,a medicine+sham EA(Med+sham EA)group,a medicine+EA(Med+EA)group。

Potential application of the Kampo medicine goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy （CIPN） is one of the most common and severe adverse effects related to cancer treatment. Unfortunately, although several agents and protocols have been proposed, no prophylactic strategies have yet to be proven useful. Therefore, new alternative therapies have been considered for CIPN prevention. Herbal medicine in Japan, called Kampo medicine, is derived from traditional Chinese medicine. Goshajinkigan （GJG） is a Kampo medicine, that is comprised of ten herbs. The aim of this work is to analyse the results of pre-clinical and clinical studies on the potential applications of GJG in CIPN prevention.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy

Circular RNAs(circRNAs)play a vital role in diabetic peripheral neuropathy.However,their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood.Here,we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls.Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group.Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation.A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs.circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy.Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin(PLLP)expression.Moreover,overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function.The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p,while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration.These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients,improving myelin sheath structure and nerve function.Thus,this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Autophagy-targeting modulation to promote peripheral nerve regeneration

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.

Acupuncture in diabetic peripheral neuropathy-neurological outcomes of the randomized acupuncture in diabetic peripheral neuropathy trial

BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of diabetes mellitus and can lead to serious complications.Therapeutic strategies for pain control are available but there are few approaches that influence neurological deficits such as numbness.AIM To investigate the effectiveness of acupuncture on improving neurological deficits in patients suffering from type 2 DPN.METHODS The acupuncture in DPN(ACUDPN)study was a two-armed,randomized,controlled,parallel group,open,multicenter clinical trial.Patients were randomized in a 1:1 ratio into two groups:The acupuncture group received 12 acupuncture treatments over 8 wk,and the control group was on a waiting list during the first 16 wk,before it received the same treatment as the other group.Both groups received routine care.Outcome parameters were evaluated after 8,16 and 24 wk and included neurological scores,such as an 11-point numeric rating scale(NRS)11 for hypesthesia,neuropathic pain symptom inventory(NPSI),neuropathy deficit score(NDS),neuropathy symptom score(NSS);nerve conduction studies(NCS)were assessed with a handheld point-of-care device.RESULTSSixty-two participants were included.The NRS for numbness showed a difference of 2.3(P<0.001)in favor of theacupuncture group,the effect persisted until week 16 with a difference of 2.2(P<0.001)between groups and 1.8points at week 24 compared to baseline.The NPSI was improved in the acupuncture group by 12.6 points(P<0.001)at week 8,the NSS score at week 8 with a difference of 1.3(P<0.001);the NDS and the TNSc score improvedfor the acupuncture group in week 8,with a difference of 2.0 points(P<0.001)compared to the control group.Effects were persistent in week 16 with a difference of 1.8 points(P<0.05).The NCS showed no meaningfulchanges.In both groups only minor side effects were reported.CONCLUSION Study results suggest that acupuncture may be beneficial in type 2 diabetic DPN and seems to lead to a reductionin neurological deficits.No serious adverse events were recorded and the adherence to treatment was high.Confirmatory randomized sham-controlled clinical studies with adequate patient numbers are needed to confirmthe results.

Advances in cardiovascular-related biomarkers to predict diabetic peripheral neuropathy

Diabetic peripheral neuropathy(DPN)is a common chronic complication of diabetes mellitus.One of the most common types is distal symmetric polyneuropathy,which begins as bilateral symmetry pain and hyperesthesia and gradually progresses into hypoesthesia with nerve fibre disorder and is frequently accompanied by depression and anxiety.Notably,more than half of patients with DPN can be asymptomatic,which tends to delay early detection.Furthermore,the study of adverse outcomes showed that DPN is a prominent risk factor for foot ulceration,gangrene and nontraumatic amputation,which decreases quality of life.Thus,it is essential to develop convenient diagnostic biomarkers with high sensitivity for screening and early intervention.It has been reported that there may be common pathways for microvascular and macrovascular complications of diabetes.The pathogenesis of both disorders involves vascular endothelial dysfunction.Emerging evidence indicates that traditional and novel cardiovascularrelated biomarkers have the potential to characterize patients by subclinical disease status and improve risk prediction.Additionally,beyond traditional cardiovascular-related biomarkers,novel cardiovascular-related biomarkers have been linked to diabetes and its complications.In this review,we evaluate the association between major traditional and nontraditional car-diovascular-related biomarkers of DPN,such as cardiac troponin T,B-type natriuretic peptide,Creactive protein,myeloperoxidase,and homocysteine,and assess the evidence for early risk factor-based management strategies to reduce the incidence and slow the progression of DPN.