A型肉毒素在皮肤科的应用

A型肉毒素是由肉毒梭状芽胞杆菌在其繁殖过程中产生的细菌外毒素,可抑制神经末梢乙酰胆碱的释放,使肌肉松弛,在整形外科、神经内科、眼科等多个科室均有应用。随着医学实践及科研实验的不断深入,发现A型肉毒素还具有抑制纤维细胞增生、阻止支配汗腺的神经末梢释放乙酰胆碱、阻断相关疼痛介质的释放或传导及抑制炎性神经递质等作用,在防疤、止汗、止痛、抗瘙痒、减少皮脂腺分泌等方面均有一定的疗效。基于此,文章从美容医疗及疾病治疗两方面分析A型肉毒素在皮肤科的应用。     

Phase I Dose-Escalation Study of SCB01A,a Microtubule Inhibitor with Vascular Disrupting Activity,in Patients with Advanced Solid Tumors

Lessons Learned

• SCB01A is a novel microtubule inhibitor with vascular disrupting activity.
• This first‐in‐human study demonstrated SCB01A safety, pharmacokinetics, and preliminary antitumor activity.
• SCB01A is safe and well tolerated in patients with advanced solid malignancies with manageable neurotoxicity.

BackgroundSCB01A, a novel microtubule inhibitor, has vascular disrupting activity.MethodsIn this phase I dose‐escalation and extension study, patients with advanced solid tumors were administered intravenous SCB01A infusions for 3 hours once every 21 days. Rapid titration and a 3 + 3 design escalated the dose from 2 mg/m² to the maximum tolerated dose (MTD) based on dose‐limiting toxicity (DLT). SCB01A‐induced cellular neurotoxicity was evaluated in dorsal root ganglion cells. The primary endpoint was MTD. Safety, pharmacokinetics (PK), and tumor response were secondary endpoints.ResultsTreatment‐related adverse events included anemia, nausea, vomiting, fatigue, fever, and peripheral sensorimotor neuropathy. DLTs included grade 4 elevated creatine phosphokinase (CPK) in the 4 mg/m² cohort; grade 3 gastric hemorrhage in the 6.5 mg/m² cohort; grade 2 thromboembolic event in the 24 mg/m² cohort; and grade 3 peripheral sensorimotor neuropathy, grade 3 elevated aspartate aminotransferase, and grade 3 hypertension in the 32 mg/m² cohort. The MTD was 24 mg/m², and average half‐life was ~2.5 hours. The area under the curve‐dose response relationship was linear. Nineteen subjects were stable after two cycles. The longest treatment lasted 24 cycles. SCB01A‐induced neurotoxicity was reversible in vitro.ConclusionThe MTD of SCB01A was 24 mg/m² every 21 days; it is safe and tolerable in patients with solid tumors.     

Expressions of conventional vitellogenin and vitellogenin-like A in worker brains are associated with a nursing task in a ponerine ant

In eusocial insect colonies, non-reproductive workers often perform different tasks. Tasks of an individual worker are shifted depending on various factors, e.g., age and colony demography. Although a vitellogenin (Vg) gene play regulatory roles in both reproductive and non-reproductive division of labours in a honeybee, it has been shown that the insect Vg underwent multiple gene duplications and sub-functionalisation, especially in apical ant lineages. The regulatory roles of duplicated Vgs were suggested to change evolutionarily among ants, whereas such roles in phylogenetically basal ants remain unclear. Here, we examined the expression patterns of conventional Vg (CVg), Vg-like A, Vg-like B and Vg-like C, as well as Vg receptor, during the task shift in an age-dependent manner and under experimental manipulation of colony demography in a primitive ant Diacamma sp. Expressions of CVg and Vg-like A in a brain were associated with a nursing task. It is suggested that associations of brain expressions of these Vgs with worker tasks were acquired in the basal ant lineage, and that such Vg functions could have sub-functionalised in the derived ant lineage.     

Peripheral blood inflammatory markers in predicting prognosis in patients with COVID‐19. Some differences with influenza A

BackgroundTo evaluate the ability of peripheral blood inflammatory markers in predicating the typing of COVID‐19, prognosis, and some differences between COVID‐19 and influenza A patients.MethodsClinical data on 285 cases laboratory‐confirmed as SARS‐CoV‐2 infection were obtained from a Wuhan local hospital''s electronic medical records according to previously designed standardized data collection forms. Additional 446 Influenza A outpatients’ hematologic data were enrolled for comparison.ResultsNLR, SII, RLR, PLR, HsCRP, and IL‐6 were significant higher and LMR was lower in severe COVID‐19 patients than in mild COVID‐19 patients (p < .001). PLR and LMR were lower in the individuals with influenza A than those with COVID‐19 (p < .01). COVID‐19 patients with higher levels of NLR, SII, RLR, PLR, HsCRP, and IL‐6 and lower LMR were significantly associated with the severe type. AUC of NLR (0.76) was larger while the specificity of IL‐6 (86%) and sensitivity of HsCRP (89%) were higher than other inflammatory markers in predicating the typing of COVID‐19. PT had obvious correlation with all the inflammatory markers except RPR. NLR showed positive correlations with AST, TP, BUN, CREA, PT, and D‐dimer. Patients with high IL‐6 levels have a relatively worse prognosis (HR = 2.30).ConclusionPeripheral blood inflammatory markers reflected the intensity of inflammation and associated with severity of COVID‐19.NLR was more useful to predict severity as well as IL‐6 to predict prognosis of COVID‐19. PLR and LMR were initially found to be higher in SARS‐CoV‐2 virus‐infected group than in influenza A.     

A modality-specific somatosensory evoked potential test protocol for clinical evaluation: A feasibility study

ObjectiveWe aimed to establish an objective neurophysiological test protocol that can be used to assess the somatosensory nervous system.MethodsIn order to assess most fiber subtypes of the somatosensory nervous system, repetitive stimuli of seven different modalities (touch, vibration, pinprick, cold, contact heat, laser, and warmth) were synchronized with the electroencephalogram (EEG) and applied on the cheek and dorsum of the hand and dorsum of the foot in 21 healthy subjects and three polyneuropathy (PNP) patients. Latencies and amplitudes of the modalities were assessed and compared. Patients received quantitative sensory testing (QST) as reference.ResultsWe found reproducible evoked potentials recordings for touch, vibration, pinprick, contact-heat, and laser stimuli. The recording of warm-evoked potentials was challenging in young healthy subjects and not applicable in patients. Latencies were shortest within Aβ-fiber-mediated signals and longest within C-fibers. The test protocol detected function loss within the Aβ-fiber and Aδ-fiber-range in PNP patients. This function loss corresponded with QST findings.ConclusionIn this pilot study, we developed a neurophysiological test protocol that can specifically assess most of the somatosensory modalities. Despite technical challenges, initial patient data appear promising regarding a possible future clinical application.SignificanceEstablished and custom-made stimulators were combined to assess different fiber subtypes of the somatosensory nervous system using modality-specific evoked potentials.     

A型肉毒素在皮肤科疾病治疗中的进展

A型肉毒素是肉毒梭状芽孢杆菌在繁殖过程中分泌的A型毒性蛋白质,具有很强的神经毒性。其在皮肤美容方面的疗效显著而被熟知。除皮肤美容外,临床实践和前期研究均证实A型肉毒素在治疗皮肤病方面亦有明显疗效,且部分疾病经治疗预后明显优于传统治疗,如瘢痕与多汗症等。     

《临证指南医案》痹证用药特点分析

目的探讨《临证指南医案》痹证用药特点。方法 运用数据挖掘技术统计药物使用频次、性味归经并进行关联规则、聚类、复杂网络分析等。结果 筛选出83首处方,共涉及中药125味，使用频次前5位依次为桂枝、茯苓、白术、当归、苦杏仁，功效类别以补虚药为主，性味以甘温最多，归经主要涉及肺、脾、肝、心、肾、胃；关联规则得到10对常见组合，高频中药聚为4类，复杂网络分析得到1个核心组合。结论 叶氏常从络病角度治痹，或通、或补、或通补皆施，重视肺脾，注重调和气血营卫，擅长通补奇经治法。     

乳腺原发癌和淋巴结转移癌中ALDH1A1和TGF-β1的表达及预后价值

目的 探讨乳腺原发癌和相应淋巴结转移癌中乙醛脱氢酶1(ALDH1A1)和转化生长因子-β1(TGF-β1)的表达情况及与患者预后的相关性,并探讨ALDH1A1与TGF-β1之间的相关性。方法 收集有淋巴结转移的乳腺非特殊型浸润性癌197例,采用免疫组化方法检测ALDH1A1和TGF-β1在原发癌及相应淋巴结转移癌中的表达情况,并对临床病理参数及预后进行统计学分析。结果 ALDH1A1和TGF-β1在乳腺原发癌和相应淋巴结转移癌中表达的一致率分别为87.82%和86.80%,两者呈明显的正相关(P＜0.05);Kaplan-Meier生存曲线结合Log-rank检验显示,在原发癌和淋巴结转移癌中,ALDH1A1和TGF-β1均为不良预后因素(P＜0.05);单因素Cox比例风险回归模型分析显示,组织学分级、肿块大小、阳性淋巴结个数、原发癌和转移癌中ALDH1A1和TGF-β1均是患者预后的危险因素(P＜0.05),多因素分析结果显示原发癌ALDH1A1、转移癌TGF-β1及阳性淋巴结个数是患者预后的独立危险因素(P＜0.05);Spearman相关性分析显示,在乳腺原发癌和相应淋巴结转移癌中,ALDH1A1和TGF-β1均呈明显正相关(P＜0.05)。结论 ALDH1A1和TGF-β1的表达在原发癌和相应淋巴结转移癌中呈正相关,且均与预后相关。ALDH1A1和TGF-β1的表达存在正相关,原发癌ALDH1A1和转移癌TGF-β1是判断乳腺癌预后的独立影响因素。     

不同照射方式下核黄素-A波紫外线兔巩膜胶原交联术对兔巩膜成纤维细胞生物力学特性的影响

目的　研究不同照射方式下核黄素-A波紫外线兔巩膜胶原交联术对兔巩膜成纤维细胞生物力学特性的影响。方法　取健康新西兰大白兔24只，随机将兔平均分为A、B两组，每组选取左眼为实验眼，右眼为对照眼。麻醉后暴露左眼鼻上方巩膜。在该处巩膜滴加5-磷酸核黄素5 min后，用波长为370 nm的紫外线灯照射。A组的照射时间为30 min，能量密度为3.0 mW·cm^-2；B组的照射时间为9 min，能量密度为10.0 mW·cm^-2。照射期间，每2 min滴加1次5-磷酸核黄素溶液，以保持巩膜的湿润。术后60 d，处死实验兔，培养实验眼交联部位及对照眼相应部位的巩膜成纤维细胞，用细胞微管吸吮实验检测巩膜成纤维细胞的杨氏模量、表观黏性。结果　A、B两组实验眼巩膜细胞的杨氏模量、表观黏性均较各自对照眼显著增强，差异均有统计学意义（均为P＜0.05）；而A、B两组实验眼间、及对照眼间巩膜细胞的杨氏模量、表观黏性差异无统计学意义（均为P＞0.05）。以上结果表明，交联术后巩膜细胞的黏弹性发生了明显的变化，黏弹性显著升高。而两种照射方式之间巩膜细胞的黏弹性无显著差异。结论　两种不同的照射方式，均能使巩膜成纤维细胞的生物力学性能发生显著增强，而两种照射方式之间并未见明显的差别。