Diffusion Tensor Imaging Evaluates Effects of Acupoint Injection at Zusanli (ST36) for Type 2 Diabetic Peripheral Neuropathy.

BACKGROUND Acupoint injection is a therapeutic method that combines acupuncture and Western medicine and shows good curative effects for neuropathies. This study aimed to explore the efficacy of acupoint injection for treating diabetic peripheral neuropathy (DPN) by magnetic resonance neuroimaging (MRN). MATERIAL AND METHODS Forty patients with DPN were randomly divided into an acupoint injection group (AI; n=20) and intramuscular injection group (MI; n=20). The AI group received an acupoint injection of mecobalamin at acupoint Zusanli (S36); the MI group received intramuscular injection of mecobalamin. The curative effect was evaluated by the Toronto Clinical Neuropathy Score and diffusion tensor imaging (DTI). RESULTS The neuropathy scores of both groups decreased from baseline (AI 9.31±2.36; MI 9.34±2.54) to after the 2-week treatment (AI 7.12±1.87; MI 7.86±2.11); the differences were not significant. The fractional anisotropy (FA) value showed significant differences on the common peroneal nerve (AI 0.36±0.04; MI 0.31±0.05; P<0.05) and tibial nerve (AI 0.38±0.07; MI 0.34±0.06; P<0.05) after treatment. Likewise, apparent diffusion coefficient (ADC) values between groups showed significant differences for the common peroneal nerve (AI 1.44±0.17×10⁻³ mm²/s; MI 1.61±0.20×10⁻³ mm²/s; P<0.05) and tibial nerve (AI 1.54±0.22×10-3 mm²/s; MI 1.60±0.17 10⁻³ mm²/s; P<0.05). CONCLUSIONS Patients with DPN showed lower nerve FA and higher ADC in DTI-MRN. The acupoint injection of mecobalamin could treat DPN and repair the damaged nerves, which was shown by elevated FA and lowered ADC. Our study provides clinical evidence for the application of acupoint injection therapy and the evaluation of DPN by MRN.

Improvement of the Clinical and Psychological Profile of Patients with Autism after Methylcobalamin Syrup Administration.

(1) Background: Autism, also known as autism-spectrum disorder, is a pervasive developmental disorder affecting social skills and psychological status in particular. The complex etiopathogenesis of autism limits efficient therapy, which leads to problems with the normal social integration of the individual and causes severe family distress. Injectable methylcobalamin was shown to improve the clinical status of patients via enhanced cell oxidative status and/or methylation capacity. Here we tested the efficiency of a syrup form of methylcobalamin in treating autism. (2) Methods: Methylcobalamin was administered daily at 500 µg dose to autistic children and young adults (n = 25) during a 200-day period. Clinical and psychological status was evaluated by parents and psychologists and plasma levels of reduced and oxidized glutathione, vitamin B12, homocysteine, and cysteine were determined before the treatment, and at day 100 and day 200 of the treatment. (3) Results: Good patient compliance was reported. Methylcobalamin treatment gradually improved the overall clinical and psychological status, with the highest impact in the social domain, followed by the cognitive, behavioral and communication characteristics. Changes in the clinical and psychological status were strongly associated with the changes in the level of reduced glutathione and reduced/oxidized glutathione ratio. (4) Conclusion: A high dose of methylcobalamin administered in syrup form ameliorates the clinical and psychological status of autistic individuals, probably due to the improved oxidative status.

Based on proteomics to explore the mechanism of mecobalamin promoting the repair of injured peripheral nerves.

Mecobalamin is commonly used in the adjuvant intervention of various peripheral nerve injuries. Actin cytoskeleton plays a role in the regeneration of myelin and axon. Therefore, the purpose of this study was to explore the possibility of mecobalamin regulating actin cytoskeleton in repairing nerve injury. In this study, a crush injury on the right sciatic nerve of two groups of rats (12 in each group) was established. The control group was only given normal saline (i.g.), and the intervention group was given mecobalamin 1 mg/kg (i.g.). The rats were sacrificed on 28th day and the injured nerves were collected for proteomics. The result shows that regulation of actin cytoskeleton pathway changed significantly. The expression of protein Vav1 was verified by Western blot and immunofluorescence. In the intervention group, the nerve fiber structure was complete, the axons were dense and symmetrical, and the myelin sheath was compact and uniform in thickness. The positive rate of myelin basic protein and ßⅢ-tubulin was higher than that in the control group. The findings of the study show that mecobalamin regulates the actin cytoskeleton in the repair of nerve damage and upregulates Vav1 in the regulation of actin cytoskeleton pathway.

Methylcobalamin Alleviates Neuronal Apoptosis and Cognitive Decline Induced by PM2.5 Exposure in Mice.

BACKGROUND: Fine particulate matter (particulate matter 2.5, PM2.5) is considered one of the harmful factors to neuronal functions. Apoptosis is one of the mechanisms of neuronal injury induced by PM2.5. Methylcobalamine (MeCbl) has been shown to have anti-apoptotic and neuroprotective effects. OBJECTIVE: The current work tried to explore the neuroprotective effects and mechanisms that MeCbl protects mice against cognitive impairment and neuronal apoptosis induced by chronic real-time PM2.5 exposure. METHODS: Twenty-four 6-week-old male C57BL/6 mice were exposed to ambient PM2.5 and fed with MeCbl for 6 months. Morris water maze was used to evaluate the changes of spatial learning and memory ability in mice. PC12 cells and primary hippocampal neurons were applied as the in vitro model. Cell viability, cellular reactive oxygen species (ROS) and the expressions of apoptosis-related proteins were examined. And cells were stained with JC-1 and mitochondrial membrane potential was evaluated. RESULTS: In C57BL/6 mice, MeCbl supplementation alleviated cognitive impairment and apoptosis-related protein expression induced by PM2.5 exposure. In in vitro cell model, MeCbl supplementation could effectively rescue the downregulation of cell viability induced by PM2.5, and inhibited the increased levels of ROS, cellular apoptosis, and the expressions of apoptosis related proteins related to PM2.5 treatment, which may be associated with modulation of mitochondrial function. CONCLUSION: MeCbl treatment alleviated cognitive impairment and neuronal apoptosis induced by PM2.5 both in vivo and in vitro. The mechanism for the neuroprotective effects of MeCbl may at least be partially dependent on the regulation of mitochondrial apoptosis.

The efficacy of acoustic therapy versus oral medication for chronic tinnitus: A meta-analysis.

PURPOSE: To compare the efficacy of acoustic therapy (AT) and drug therapy (DT) for chronic tinnitus. METHODS: We searched Pubmed, ScienceDirect, Chinese Journal Full-text Database (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Embase, and Cochrane Library from the establishment of the database to December 2019. Meta-analysis was performed on the Tinnitus Handicap Inventory (THI) score and Visual Analogue Scale (VAS) with included literature using Revman 5.3 software. RESULTS: A total of 18 documents were included, including 16 Chinese documents and 2 English documents, with 1774 patients (including 962 patients treated with AT and 812 patients treated with DT). The effect of AT (by the number of cases or ears) is better than that of DT (P < 0.05). After treatment, the THI value of AT was more evident than that of DT (WMD = -4.25, (-13.24, -5.29)). And the VAS value of AT was significantly lower than that of DT (WMD = -0.73, (-1.31, -0.15)). CONCLUSION: Compared with DT, AT can significantly improve the efficacy of tinnitus and reduce the symptoms of tinnitus patients. Clinically, it can vigorously promote the application value of treating tinnitus by sound.

Redox-Linked Coordination Chemistry Directs Vitamin B12 Trafficking.

Metals are partners for an estimated one-third of the proteome and vary in complexity from mononuclear centers to organometallic cofactors. Vitamin B12 or cobalamin represents the epitome of this complexity and is the product of an assembly line comprising some 30 enzymes. Unable to biosynthesize cobalamin, mammals rely on dietary provision of this essential cofactor, which is needed by just two enzymes, one each in the cytoplasm (methionine synthase) and the mitochondrion (methylmalonyl-CoA mutase). Brilliant clinical genetics studies on patients with inborn errors of cobalamin metabolism spanning several decades had identified at least seven genetic loci in addition to the two encoding B12 enzymes. While cells are known to house a cadre of chaperones dedicated to metal trafficking pathways that contain metal reactivity and confer targeting specificity, the seemingly supernumerary chaperones in the B12 pathway had raised obvious questions as to the rationale for their existence.With the discovery of the genes underlying cobalamin disorders, our laboratory has been at the forefront of ascribing functions to B12 chaperones and elucidating the intricate redox-linked coordination chemistry and protein-linked cofactor conformational dynamics that orchestrate the processing and translocation of cargo along the trafficking pathway. These studies have uncovered novel chemistry that exploits the innate chemical versatility of alkylcobalamins, i.e., the ability to form and dismantle the cobalt-carbon bond using homolytic or heterolytic chemistry. In addition, they have revealed the practical utility of the dimethylbenzimidazole tail, an appendage unique to cobalamins and absent in the structural cousins, porphyrin, chlorin, and corphin, as an instrument for facilitating cofactor transfer between active sites.In this Account, we navigate the chemistry of the B12 trafficking pathway from its point of entry into cells, through lysosomes, and into the cytoplasm, where incoming cobalamin derivatives with a diversity of upper ligands are denuded by the ß-ligand transferase activity of CblC to the common cob(II)alamin intermediate. The broad reaction and lax substrate specificity of CblC also enables conversion of cyanocobalamin (technically, vitamin B12, i.e., the form of the cofactor in one-a-day supplements), to cob(II)alamin. CblD then hitches up with CblC via a unique Co-sulfur bond to cob(II)alamin at a bifurcation point, leading to the cytoplasmic methylcobalamin or mitochondrial 5'-deoxyadenosylcobalamin branch. Mutations at loci upstream of the junction point typically affect both branches, leading to homocystinuria and methylmalonic aciduria, whereas mutations in downstream loci lead to one or the other disease. Elucidation of the biochemical penalties associated with individual mutations is providing molecular insights into the clinical data and, in some instances, identifying which cobalamin derivative(s) might be therapeutically beneficial.Our studies on B12 trafficking are revealing strategies for cofactor sequestration and mobilization from low- to high-affinity and low- to high-coordination-number sites, which in turn are regulated by protein dynamics that constructs ergonomic cofactor binding pockets. While these B12 lessons might be broadly relevant to other metal trafficking pathways, much remains to be learned. This Account concludes by identifying some of the major gaps and challenges that are needed to complete our understanding of B12 trafficking.

Salviae miltiorrhizae and ligustrazine hydrochloride injection combined with mecobalamin for treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

OBJECTIVE: Currently, it is unclear whether the salviae miltiorrhizae (Danshen Salvia) and ligustrazine hydrochloride (Chuanxiong Chuanxiong) (SMLH) injection combined with mecobalamin can improve diabetic peripheral neuropathy (DPN). We conducted a systematic analysis to evaluate the clinical effects of SMLH injection combined with mecobalamin for treating DPN. METHODS: Seven databases, including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Database (Wang Fang), Chinese Biomedical Literature Database (CBM), and VIP Database for Chinese Technical Periodicals (VIP) were searched for systematic literature retrieval. Each database was searched up to 2020 to identify randomized controlled trials on DPN treated with SMLH injection combined with mecobalamin. We used the RevMan 5.3 and Stata 14.0 software to assess the risk of bias in the included trials. RESULTS: A total of 15 publications, including 1349 samples, were reviewed. The total effective rate of SMLH injection combined with mecobalamin was 31% higher than that of mecobalamin alone (95% confidence interval [CI] = 1.23-1.38; P < .00001). The experimental group showed a significant increase in the motor conduction velocity (MCV) of the peroneal nerve (weighted mean difference [WMD] = 4.81, 95% CI 3.53-6.09; P < .00001). In addition, SMLH injection combined with mecobalamin showed a statistical significant effect on the sensory conduction velocity (SCV) of the peroneal nerve (WMD = 5.03, 95% CI = 4.16-5.90; P < .00001), and MCV of the median nerve (WMD = 5.38, 95% CI = 4.05-6.72; P < .00001). The WMD for the change in SCV in the median nerve was 4.89 m/s (95% CI = 3.88-5.89; P < .00001). The P-values of the Egger and Begg tests were 0.967 and 0.961, respectively, indicating no publication bias. Subgroup and sensitivity analyses indicated that the results for MCV and SCV of the peroneal nerve and the median nerve were stable. CONCLUSION: SMLH injection combined with mecobalamin can improve DPN, compared with mecobalamin alone.

Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial.

AIM: To investigate the effect of normalizing vitamin B12 (B12) levels with oral B12 (methylcobalamin) 1000 µg/day for one year in patients with diabetic neuropathy (DN). PATIENTS AND METHODS: In this prospective, double-blind, placebo-controlled trial, 90 patients with type 2 diabetes on metformin for at least four years and both peripheral and autonomic DN were randomized to an active treatment group (n = 44) receiving B12 and a control group (n = 46) receiving a placebo. All patients had B12 levels less than 400 pmol/L. Subjects underwent measurements of sural nerve conduction velocity (SNCV), sural nerve action potential (amplitude) (SNAP), and vibration perception threshold (VPT), and they performed cardiovascular autonomic reflex tests (CARTs: mean circular resultant (MCR), Valsalva test, postural index, and orthostatic hypotension). Sudomotor function was assessed with the SUDOSCAN that measures electrochemical skin conductance in hands and feet (ESCH and ESCF, respectively). We also used the Michigan Neuropathy Screening Instrument Questionnaire and Examination (MNSIQ and MNSIE, respectively) and questionnaires to evaluate quality of life (QoL) and level of pain (pain score). RESULTS: B12 levels increased from 232.0 ± 71.8 at baseline to 776.7 ± 242.3 pmol/L at follow-up, p < 0.0001, in the active group but not in the control group. VPT, MNSIQ, QoL, pain score, SNCV, SNAP, and ESCF significantly improved in the active group (p < 0.001, p = 0.002, p < 0.0001, p < 0.000, p < 0.0001, p < 0.0001, and p = 0.014, respectively), whereas CARTS and MNSIE improved but not significantly. MCR, MNSIQ, SNCV, SNAP, and pain score significantly deteriorated in the control group (p = 0.025, p = 0.017, p = 0.045, p < 0.0001, and p < 0.0001, respectively). CONCLUSIONS: The treatment of patients with DN with 1 mg of oral methylcobalamin for twelve months increased plasma B12 levels and improved all neurophysiological parameters, sudomotor function, pain score, and QoL, but it did not improve CARTS and MNSIE.

Myeloradiculoneuropathy due to vitamin B12 deficiency: an unusual clinical and radiological presentation.

A 42-year-old man from rural India presented with asymmetric progressive paraparesis mimicking compressive dorsal myelopathy, followed by distal upper limb, truncal and neck-flexor weakness, further complicated by acute urinary retention. His sensory deficits were marked by loss of joint position sense (JPS) and graded loss of vibration sense, along with a definite sensory level. Deep tendon jerks were hypo-to-areflexic, plantar was bilaterally extensor. He had become less attentive and occasionally failed to keep track with conversations. A syndromic diagnosis of myeloradiculoneuropathy with cognitive impairments was made. Further tailored investigations revealed vitamin B12 deficiency with positive anti-parietal cell antibody. Diagnosis of subacute combined cord degeneration (SACD) was confirmed. Neuro-imaging revealed intramedullary intensity changes only along lateral aspect of spinal cord instead of characteristic posterior involvement. Following parenteral vitamin B12 supplementation, patient started showing improvement in motor power and subjective sensory symptoms. His bladder symptoms persisted initially, however recovered finally after 6 months.

Efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy: A protocol for systematic review and meta-analysis.

BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. METHODS: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. RESULTS: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. CONCLUSION: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KPW5E.