人参内生菌的研究进展

内生菌由细菌、真菌、古菌和原生生物组成，它们生活在植物的活体组织中，具有丰富的次级代谢产物多样性。人参内生菌在人参的生长发育、次级代谢产物的生成和环境适应等方面均有重要的促进作用，对人参的产量和品质有较大影响。随着人们在微生物领域研究的深入，高通量测序技术已经成为研究植物内生菌的重要方法。文章主要从人参内生菌分离与鉴定研究方法、人参内生菌的多样性、人参内生菌及其次级代谢产物的活性、人参内生菌对宿主的影响等4个方面对人参内生菌近年来的研究进展进行讨论，并对其发展方向提出展望，以期为药用植物内生菌研究和品质改良提供新思路、新方法。     

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.     

Enlarged high frequency oscillations of the median nerve somatosensory evoked potential and survival in amyotrophic lateral sclerosis

ObjectiveA large N20 and P25 of the median nerve somatosensory evoked potential (SEP) predicts short survival in amyotrophic lateral sclerosis (ALS). We investigated whether high frequency oscillations (HFOs) over N20 are enlarged and associated with survival in ALS.MethodsA total of 145 patients with ALS and 57 healthy subjects were studied. We recorded the median nerve SEP and measured the onset-to-peak amplitude of N20 (N20o-p), and peak-to-peak amplitude between N20 and P25 (N20p-P25p). We obtained early and late HFO potentials by filtering SEP between 500 and 1 kHz, and measured the peak-to-peak amplitude. We followed up patients until endpoints (death or tracheostomy) and analyzed the relationship between SEP or HFO amplitudes and survival using a Cox analysis.ResultsPatients showed larger N20o-p, N20p-P25p, and early and late HFO amplitudes than the control values. N20p-P25p was associated with survival periods (p = 0.0004), while early and late HFO amplitudes showed no significant association with survival (p = 0.4307, and p = 0.6858, respectively).ConclusionsThe HFO amplitude in ALS is increased, but does not predict survival.SignificanceThe enlarged HFOs in ALS might be a compensatory phenomenon to the hyperexcitability of the sensory cortex pyramidal neurons.     

2010—2016年重庆市中毒病例流行病学特征及影响因素分析

对2010年1月—2016年7月重庆市中毒救治指定医疗机构收治的2 497例中毒患者进行回顾性分析。结果显示，中毒患者中男性1 230例（49.3%）、女性1 267例（50.7%）；分布最多的3个年龄段依次是41~50岁（18.5%）、≤10岁（16.4%）和21~30岁（13.0%）；死亡16例，病死率0.6%。中毒类型构成排前三位的是细菌（33.8%）、化学品（32.2%）、植物（14.8%）。中毒预后多因素Logistic回归分析结果显示重度中毒患者结局死亡的可能性是轻度患者的1 102倍。提示重庆市应重点关注农村地区41~50岁人群的细菌、化学品、药物中毒，同时应该加强儿童中毒防控工作。     

股骨转子间骨折的稳定性重建概念演化与研究进展

目的总结近年来股骨转子间骨折在稳定性重建方面的概念演化与研究进展。方法查阅国内外相关文献并结合自身经验，从股骨转子间骨折的解剖特点、稳定型骨折与不稳定型骨折分类、稳定性复位与不稳定性复位、术中加压初始稳定与术后滑动二次稳定、内固定术后稳定性评估、早期下地站立负重等方面进行总结分析。结果股骨转子间骨折发生于股骨颈干骺端转换区，具有天然的内翻不稳定倾向。骨折复位质量是影响后续内固定物安放的最重要前提因素。判断骨折复位质量有对线和对位两方面，对线采用 Garden 指数；在对位方面，随着皮质对位理念（正性、中性、负性）的提出，特别强调前内侧皮质的相互砥住支撑（解剖、正性），是获得骨折稳定性复位的关键，而不再强调后内侧小转子骨块的作用。术后影像学的稳定性评分为早期下地站立负重提供了量化指标。但术中的前内侧皮质支撑复位，在术后头颈骨块滑动获得二次稳定的过程中，仍有皮质对位丢失现象，需研究其危险因素和防范措施。结论股骨转子间骨折在取得良好对线的基础上，只要获得了前内侧皮质的相互砥住和支撑，并用内固定器械维持住，就获得了术后稳定性。术后稳定性评分优良者，可以安全地早期下地负重、站立行走活动。     

Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.