Preliminary Risk assessment for Acrylamide and Peripheral Neuropathy

Acrylamide (ACM) is a high-volume industrial chemical with diverse uses in manufacturing, construction and laboratory research. ACM is a well-established neurotoxic agent causing peripheral neuropathy with impairment in the arms and legs of exposed workers, most thoroughly studied in Swedish tunnel workers exposed to ACM grouting. A quantitative risk assessment was performed to assess ACM risk to workers. Using data from a published paper investigating peripheral neuropathies in Chinese chemical workers, estimates of exposure response for vibration perception threshold and nerve conduction velocities were calculated, based on hemoglobin adducts and air concentrations as exposure metrics. The benchmark dose procedure was applied in order to calculate excess risks of impairment, defined as adverse performance exceeding the 95^th percentile in unexposed populations, at various concentrations of airborne ACM exposure. Under the assumptions in this risk assessment, after three years of inhalation exposure at 0.3 mg/m³, the excess attributable impairment manifest in vibration perception and nerve conduction velocity is estimated to occur in 1-2% of workers. For 10 years at 0.3 mg/m³ ACM inhalation (equivalent to 3 years at 1.0 mg/m³) the excess prevalence of impairment would be 2-14% of workers, assuming the effect continues to accrue linearly in time. Using published data, the risks of impairment from peripheral neuropathy attributable to exclusively airborne ACM exposure can be predicted for exposure periods less than 10 years. The risks associated with dermal and airborne ACM exposures can be estimated by characterizing working process environments using ACM Hb-adduct levels and possibly monitored with urinary biomarkers.     

甲状腺癌术后复发再手术中甲状旁腺和神经保护

甲状腺癌是一种十分常见的恶性肿瘤，其病理类型大多数为分化型甲状腺癌，经规范化治疗，预后较好，但仍有部分病人复发，且长期随访，可有高达30%以上的复发或转移率。因此，再次手术是甲状腺外科医师不可避免的问题，甚至在未来一段时间会成为一个临床常见情况。再次手术，尤其是Ⅵ区淋巴结复发的再次手术，往往有较高的手术难度和风险，需要谨慎地选择手术时机和入路，术中应用神经监测与传统显露技术相结合以保护喉返神经，运用传统识别和保护手法，选择性应用纳米炭、甲状旁腺素试纸、近红外自体荧光显像等技术以保护甲状旁腺功能。     

KDM6B epigenetically regulated-interleukin-6 expression in the dorsal root ganglia and spinal dorsal horn contributes to the development and maintenance of neuropathic pain following peripheral nerve injury in male rats

The lysine specific demethylase 6B (KDM6B) has been implicated as a coregulator in the expression of proinflammatory mediators, and in the pathogenesis of inflammatory and arthritic pain. However, the role of KDM6B in neuropathic pain has yet to be studied. In the current study, the neuropathic pain was determined by assessing the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) following lumbar 5 spinal nerve ligation (SNL) in male rats. Immunohistochemistry, Western blotting, qRT-PCR, and chromatin immunoprecipitation (ChIP)-PCR assays were performed to investigate the underlying mechanisms. Our results showed that SNL led to a significant increase in KDM6B mRNA and protein in the ipsilateral L4/5 dorsal root ganglia (DRG) and spinal dorsal horn; and this increase correlated a markedly reduction in the level of H3K27me3 methylation in the same tissue. Double immunofluorescence staining revealed that the KDM6B expressed in myelinated A- and unmyelinated C-fibers in the DRG; and located in neuronal cells, astrocytes, and microglia in the dorsal horn. Behavioral data showed that SNL-induced mechanical allodynia and thermal hyperalgesia were impaired by the treatment of prior to i.t. injection of GSK-J4, a specific inhibitor of KDM6B, or KDM6B siRNA. Both microinjection of AAV2-EGFP-KDM6B shRNA in the lumbar 5 dorsal horn and sciatic nerve, separately, alleviated the neuropathic pain following SNL. The established neuropathic pain was also partially attenuated by repeat i.t. injections of GSK-J4 or KDM6B siRNA, started on day 7 after SNL. SNL also resulted in a remarkable increased expression of interleukin-6 (IL-6) in the DRG and dorsal horn. But this increase was dramatically inhibited by i.t. injection of GSK-J4 and KDM6B siRNA; and suppressed by prior to microinjection of AAV2-EGFP-KDM6B shRNA in the dorsal horn and sciatic nerve. Results of ChIP-PCR assay showed that SNL-induced enhanced binding of STAT3 with IL-6 promoter was inhibited by prior to i.t. injection of GSK-J4. Meanwhile, the level of H3K27me3 methylation was also decreased by the treatment. Together, our results indicate that SNL-induced upregulation of KDM6B via demethylating H3K27me3 facilitates the binding of STAT3 with IL-6 promoter, and subsequently mediated-increase in the expression of IL-6 in the DRG and dorsal horn contributes to the development and maintenance of neuropathic pain. Targeting KDM6B might a promising therapeutic strategy to treatment of chronic pain.     

神经营养因子家族与宫颈癌

近年研究中，神经营养因子家族及其受体在肿瘤发生发展中的作用日益受到重视。神经营养因子家族在宫颈癌中高表达，在肿瘤发展进程中，被视为宫颈癌进展的早期事件；同时，神经营养因子促进宫颈癌细胞的增殖，增强肿瘤细胞的转移能力，并作用于宫颈癌细胞，诱导肿瘤细胞合成血管内皮生长因子，从而促进肿瘤癌灶中血管生成。本文就神经营养因子在宫颈癌发生发展中作用的最新研究进展作一综述。     

Early axonal loss predicts long-term disability in chronic inflammatory demyelinating polyneuropathy

ObjectiveTo investigate early pre-treatment nerve fiber loss as a predictor of long-term clinical outcome in chronic inflammatory demyelinating polyneuropathy (CIDP).MethodsIn 14 patients, motor and sensory conduction studies of the median, fibular, and sural nerves were performed at pre-treatment and follow-up 11–28 years later. Z-scores of amplitudes were combined as biomarkers of axonal loss and Z-scores of conduction properties as demyelination scores. The axonal loss was further examined by electromyography (EMG) and motor unit number estimation. Axonal and demyelination scores were compared to clinical outcomes in the Inflammatory Rasch-built Overall Disability Scale, the Neuropathy Impairment Score, and dynamometry.ResultsAt follow-up 12 patients walked independently, one needed support and one could not walk. The initial and follow-up axonal and demyelination scores were markedly abnormal. The initial axonal loss but not demyelination was strongly associated with both the follow-up axonal loss and the clinical measures. Moreover, delay of treatment initiation negatively influenced the axonal scores and clinical outcomes.ConclusionIn this hypothesis generating limited study, we found that axonal loss at early CIDP was highly predictive for long-term nerve fiber loss and disability.SignificanceThe study indicates that prompt initiation of treatment to prevent nerve fiber loss is necessary for outcome in CIDP.     

Clinical Study on CT-guided Modified Akupotomye in the Treatment of Lumbar Nerve Posterior Branch Compression

Objective: To observe the clinical effect of modified akupotomye closed lysis under CT guidance on compression of posterior lumbar nerve branch.Methods: Patients were diagnosed by HRCT 3-D reconstruction combined with clinical symptoms and signs.After HRCT three-dimensional reconstruction combined with clinical symptoms and signs, the patients were confirmed as posterior lumbar nerve compression.After CT accurate surface positioning, CT-guided modified akupotomye was used for closed lysis of the posterior lumbar nerve branch.Oswestry Dysfunction Index Questionnaire(ODI) was used for quantitative scoring, 7 days before and after treatment and 6 months after treatment.Results: In 62 cases, 20 cases were cured, with 25 cases markedly effective, 11 cases effective, and 36 cases ineffective.The total effective rate was 90.3%.ODI score: Self-paired t test 7 days before after treatment, P < 0.01;Before treatment and 6 months after treatment, self-paired t test(P < 0.01);Self-paired t-test was performed 7 days after treatment and 6 months after treatment(P > 0.05).Conclusion: With CT precise positioning, the modified akupotomye can be used to do closed lysis, to relieve the adhesion and compression, so that the low back pain can be relieved, with good clinical.The akupotomye closed lysis, combined with modern imaging technology has not only achieved good clinical effect, but also can improve the accuracy, safety and scientificity of akupotomye treatment.