Ecological evaluation of heavy metal pollution in the soil of Pb-Zn mines

Ecotoxicology - Soil heavy metal pollution evaluations are a necessary measure for mine ecological control projects. In this study, the heavy metals Pb, Zn and Cd were studied in mining areas,...     

基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

脑血管介入治疗患者穿刺点压迫方法的研究进展

综述了脑血管介入术穿刺点压迫方法（包括人工压迫、弹力带加压、压迫器加压、血管闭合装置压迫、止血敷料压迫、气囊加压6种）、止血压力以及压迫时间，提出由于穿刺点和压迫方法的不同，其压迫时间、减压时间和压力大小等需要进一步探讨，为脑血管介入术后患者穿刺点的临床护理提供参考。     

China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

寰枢椎后路柔性固定的生物力学研究

目的分析细棒、PEEK棒固定对寰枢关节稳定性的影响。方法采用6具新鲜成人枕骨(occipital bone,Oc)~颈椎C4节段进行测试,模拟以下手术及固定状态:①完整状态;②损伤状态:枢椎齿状突II型骨折;③坚强固定:寰枢椎均采用普通椎弓根螺钉固定,直径3.5 mm钛棒连接;④PEEK棒:直径3.5 mm的PEEK棒连接;⑤细棒:直径2.0 mm钛棒连接。采用重复测量实验设计,在完整、损伤和不同的固定状态下,通过脊柱试验机对标本分别施加1.5 N·m的前屈/后伸、左/右侧弯和左/右轴向旋转的纯力偶矩。采用Optotrak三维运动测量系统连续采集标本运动,分析寰枢椎之间角度运动范围和中性区。结果采用直径3.5 mm的钛棒,2.0 mm的细棒以及3.5 mm的PEEK棒固定后,在前屈、后伸、侧弯和旋转方向上均显著减小了固定节段的运动范围(P<0.05)。直径3.5 mm和2.0 mm的棒固定后的运动范围,在各个方向上无显著性差异。PEEK棒固定的运动范围仅在侧弯方向上大于坚强固定(P=0.005),其他方向无显著性差异。3种固定方式在屈伸、侧弯和旋转方向上均显著减小了固定节段的中性区(P<0.05)。各种固定方式之间相比较,无显著性差异(P>0.05)。结论在寰枢关节采用直径2.0 mm的细棒固定,与坚强固定的稳定性相当。采用直径3.5 mm的PEEK棒固定,在前屈、后伸、旋转方向上与坚强固定的稳定性相当,在侧弯方向上弱于坚强固定。     

Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Genomic variants within chromosome 14q32.32 regulate bone mass through MARK3 signaling in osteoblasts

Bone mineral density (BMD) is a highly heritable predictor of osteoporotic fracture. GWAS have identified hundreds of loci influencing BMD, but few have been functionally analyzed. In this study, we show that SNPs within a BMD locus on chromosome 14q32.32 alter splicing and expression of PAR-1a/microtubule affinity regulating kinase 3 (MARK3), a conserved serine/threonine kinase known to regulate bioenergetics, cell division, and polarity. Mice lacking Mark3 either globally or selectively in osteoblasts have increased bone mass at maturity. RNA profiling from Mark3-deficient osteoblasts suggested changes in the expression of components of the Notch signaling pathway. Mark3-deficient osteoblasts exhibited greater matrix mineralization compared with controls that was accompanied by reduced Jag1/Hes1 expression and diminished downstream JNK signaling. Overexpression of Jag1 in Mark3-deficient osteoblasts both in vitro and in vivo normalized mineralization capacity and bone mass, respectively. Together, these findings reveal a mechanism whereby genetically regulated alterations in Mark3 expression perturb cell signaling in osteoblasts to influence bone mass.