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.     

Oropharyngeal shedding of herpesviruses before and after BNT162b2 mRNA vaccination against COVID-19

IntroductionConcerns were raised over an increase in Bell's palsy, herpes simplex and herpes zoster after BNT162b2 vaccination, all are manifestations of herpesviruses reactivation. As herpesviruses commonly reactivate in the oropharynx, we have hypothesized that oropharyngeal shedding of herpesviruses will increase after vaccination.MethodsImmune-competent Adults, excluding those using topical steroids or manifesting symptomatic herpesvirus infection, were sampled before BNT162b2 vaccination and one week after. Herpesviruses 1–7 shedding was tested with a multiplexed PCR.ResultsIn 103 paired samples the prevalence of herpesviruses was similar before and after vaccination: HSV1, 3.9% vs. 5.8% (p = 0.75); HSV2, 0% vs. 1% (p = not applicable, NA); VZV, 0% vs. 0% (p = NA); EBV, 14.6% vs. 17.5% (p = 0.63); CMV, 0% vs. 0% (p = NA); HHV6, 4.9% vs. 7.8% (p = 0.55); HHV7, 71.8% vs. 72.8% (p = 1); any herpesvirus, 73.8% vs. 74.8% (p = 1).DiscussionWe did not find evidence for increased oropharyngeal reactivation of herpesviruses one week after BNT162b2.     

Comparison of anatomic and non-anatomic resections for very early-stage hepatocellular carcinoma: The importance of surgical resection margin width in non-anatomic resection

BackgroundThe superiority of anatomic resection (AR) over non-anatomic resection (NAR) for very early-stage hepatocellular carcinoma (HCC) has remained a topic of debate. Thus, this study aimed to compare the prognosis after AR and NAR for single HCC less than 2 cm in diameter.MethodsConsecutive patients with single HCC of diameter less than 2 cm who underwent curative hepatectomy between 1997 and 2017 were included in this retrospective study.ResultsIn total, 159 patients were included in this study. Of these, 52 patients underwent AR (AR group) and 107 patients underwent NAR (NAR group). No significant differences were noted in recurrence-free survival (RFS) and overall survival (OS) between the AR and NAR groups (P = 0.236 and P = 0.363, respectively). Multivariate analysis revealed that low preoperative platelet count and presence of satellite nodules were independent prognostic factors of RFS and OS. Wide surgical resection margin did not affect RFS (P = 0.692) in the AR group; however, in the NAR group, RFS was found to be higher with surgical resection margin widths ≥1 cm than with surgical resection margin widths <1 cm (P = 0.038).ConclusionsPrognosis was comparable between the NAR and AR groups for very early-stage HCC with well-preserved liver function. For better oncologic outcomes, surgeons should endeavor in keeping the surgical resection margin widths during NAR ≥1 cm.     

Study on Adsorption Properties of Calcined Mg–Al Hydrotalcite for Sulfate Ion and Chloride Ion in Cement Paste

In the marine environment, sulfate ions and chloride ions are abundant. Therefore, sulfate attack and chloride ion attack are common failure forms of marine concrete. Mg–Al hydrotalcite is a layered bimetallic hydroxide, which can be used as guest molecular adsorbent. In this experiment, we synthesized Mg–Al hydrotalcite, and the crystal state, surface morphology, and composition of this adsorbent were investigated by modern micro-analysis technology. Mg–Al hydrotalcite was added into the prepared target ion solution, to explore the influence of various factors on the adsorption performance of Mg–Al hydrotalcite, and then calcined Mg–Al hydrotalcite was added into cement paste, to study the mechanical properties and durability of the paste samples. The experimental results show that the optimum conditions for adsorption of chloride ions by calcined Mg–Al hydrotalcite are an adsorption time of 4 h, temperature of 35 °C, LDO (calcined Mg-Al hydrotalcite) dosage of 3.5 g/L, and a pH of 8. The adsorption effect of sulfate ion is best when the adsorption time is 6 h, the temperature is 35 °C, the dosage of LDO is 4 g/L, and the pH = 8. The optimal adsorption conditions of calcined Mg–Al hydrotalcite for chloride ion and sulfate ion are not completely the same, and the adsorption of these two ions in mixed solution shows competitive adsorption. Compared with the common paste specimens without Mg–Al hydrotalcite, the mechanical properties and deformation properties of cement specimens can be significantly improved by adding Mg–Al hydrotalcite.     

盆筋膜解剖及其与直肠固有筋膜关系研究

目的 探讨盆筋膜的结构、范围及其与直肠固有筋膜的层次关系。方法 2020年12月至2021年3月对由广东药科大学生命与生物制药学院人体解剖与胚胎学系及中山大学中山医学院人体解剖学教研室提供的12具（男性5具、女性7具）骨盆标本进行大体观察，并对Denonvilliers筋膜进行组织学观察。结合2019年12月至2021年3月中山大学附属第三医院胃肠外科收治的20例直肠癌病人（男性10例、女性10例）的盆腔磁共振图像和手术视频进行解剖学印证。结果 12具骨盆大体标本显示，盆筋膜与Gerota筋膜相延续，部分纤维于S4水平构成直肠骶骨筋膜，向下与直肠固有筋膜融合终止于联合纵肌；部分纤维与后方骶前筋膜融合构成肛提肌上筋膜及肌间纤维。Denonvilliers筋膜在盆腔前外侧约2点、10点处与盆筋膜相延续构成完整筒状结构，包绕内层由直肠固有筋膜封套的直肠系膜；除“侧韧带”处有盆腔自主神经直肠支、淋巴管、直肠中动脉相连外，两层筋膜形成完整的双筒状结构，横断面呈同心圆状。除直肠支进入直肠固有筋膜外，盆腔自主神经主要分支均位于盆筋膜内层及Denonvilliers筋膜以外，沿直肠固有筋膜轮廓游离能够避免损伤盆腔自主神经。在7具女性骨盆标本中均能见到菲薄的Denonvilliers筋膜结构。直肠癌病人的横断面磁共振图像能够看到直肠固有筋膜与外侧盆筋膜、Denonvilliers筋膜的轮廓和间隙，手术视频资料也可见到完整盆壁筋膜和Denonvilliers筋膜的轮廓。结论 直肠癌手术中，在盆筋膜、Denonvilliers筋膜与直肠固有筋膜两层结构的间隙进行分离，并保持两层筋膜的完整性，对于保证肿瘤根治性和保护排尿及性功能至关重要。     

Black beans and red kidney beans induce positive postprandial vascular responses in healthy adults: A pilot randomized cross-over study

Background and aimsConsuming pulses (dry beans, dry peas, chickpeas, lentils) over several weeks can improve vascular function and decrease cardiovascular disease risk; however, it is unknown whether pulses can modulate postprandial vascular responses. The objective of this study was to compare different bean varieties (black, navy, pinto, red kidney) and white rice for their acute postprandial effects on vascular and metabolic responses in healthy individuals.Methods and resultsThe study was designed as a single-blinded, randomized crossover trial with a minimum 6 days between consumption of the food articles. Vascular tone (primary endpoint), haemodynamics and serum biochemistry (secondary endpoints) were measured in 8 healthy adults before and at 1, 2, and 6 h after eating ¾ cup of beans or rice. Blood pressure and pulse wave velocity (PWV) were lower at 2 h following red kidney bean and pinto bean consumption compared to rice and navy bean, respectively (p < 0.05). There was greater vasorelaxation 6 h following consumption of darker-coloured beans, as shown by decreased vascular tone: PWV was lower after consuming black bean compared to pinto bean, augmentation pressure was lower after consuming black bean compared to rice and pinto bean, and wave reflection magnitude was lower after consuming red kidney bean and black bean compared to rice, navy bean, and pinto bean (p < 0.05). LDL-cholesterol concentrations were lower 6 h after black bean consumption compared to rice (p < 0.05).ConclusionOverall, red kidney and black beans, the darker-coloured beans, elicited a positive effect on the tensile properties of blood vessels, and this acute response may provide insight for how pulses modify vascular function.