响应面法优化牛蒡根多糖的提取工艺及含量预测

目的 牛蒡根中多糖的提取工艺优化及含量预测。方法 牛蒡根中多糖和葡萄糖标准品的紫外可见光谱和多糖含量数据结合R语言进行偏最小二乘法(partical least squares,PLS)建模,并进行定性和定量分析;采用响应面法优化牛蒡根多糖的提取工艺。结果 模型拟合结果表明,散点集中分布在主对角线上故最终模型的拟合效果较好,偏最小二乘法-分光光度法可用于多糖含量的快速预测;响应面法优化的最佳提取条件为提取时间55.45 min、乙醇体积分数50.78%、料液比1∶40.31;在此条件下,牛蒡根多糖的提取率为10.33%。结论 建立了预测牛蒡根多糖含量的偏最小二乘-光度法,采用响应面法优化了牛蒡根多糖的提取工艺,为提高牛蒡根资源的综合利用提供依据。     

Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice

Spinal cord astrocytes are critical in the maintenance of neuropathic pain. Connexin 43 (Cx43) expressed on spinal dorsal horn astrocytes modulates synaptic neurotransmission, but its role in nociceptive transduction has yet to be fully elaborated. In mice, Cx43 is mainly expressed in astrocytes, not neurons or microglia, in the spinal dorsal horn. Hind paw mechanical hypersensitivity was observed beginning 3 days after partial sciatic nerve ligation (PSNL), but a persistent downregulation of astrocytic Cx43 in ipsilateral lumbar spinal dorsal horn was not observed until 7 days post-PSNL, suggesting that Cx43 downregulation mediates the maintenance and not the initiation of nerve injury-induced hypersensitivity. Downregulation of Cx43 expression by intrathecal treatment with Cx43 siRNA also induced mechanical hypersensitivity. Conversely, restoring Cx43 by an adenovirus vector expressing Cx43 (Ad-Cx43) ameliorated PSNL-induced mechanical hypersensitivity. The sensitized state following PSNL is likely maintained by dysfunctional glutamatergic neurotransmission, as Cx43 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of glutamate receptor antagonists MK801 and CNQX, but not neurokinin-1 receptor antagonist CP96345 or the Ca²⁺ channel subunit α₂δ₁ blocker gabapentin. The source of this dysfunctional glutamatergic neurotransmission is likely decreased clearance of glutamate from the synapse rather than increased glutamate release into the synapse. Astrocytic expression of glutamate transporter GLT-1, but not GLAST, and activity of glutamate transport were markedly decreased in mice intrathecally injected with Cx43-targeting siRNA but not non-targeting siRNA. Glutamate release from spinal synaptosomes prepared from mice treated with either Cx43-targeting siRNA or non-targeting siRNA was unchanged. Intrathecal injection of Ad-Cx43 in PSNL mice restored astrocytic GLT-1 expression. The cytokine tumor necrosis factor (TNF) has been implicated in the induction of central sensitization, particularly through its actions on astrocytes, in the spinal cord following peripheral injury. Intrathecal injection of TNF in naïve mice induced the downregulation of both Cx43 and GLT-1 in spinal dorsal horn, as well as hind paw mechanical hypersensitivity, as observed in PSNL mice. Conversely, intrathecal treatment of PSNL mice with the TNF inhibitor etanercept prevented not only mechanical hypersensitivity but also the downregulation of Cx43 and GLT-1 expression in astrocytes. The current findings indicate that spinal astrocytic Cx43 are essential for the maintenance of neuropathic pain following peripheral nerve injury and suggest modulation of Cx43 as a novel target for developing analgesics for neuropathic pain.     

针刀结合局部阻滞治疗陈旧性半月板损伤的探索

陈旧性慢性半月板损伤在临床上为多发病,常见病,一直得不到有效的治疗,长期以往,患者的伤侧膝关节的力学平衡失调,膝关节退变速度加快,严重的出现膝关节破坏,关节僵直.我院门诊在2009年2月至2010年2月这期间采用小针刀疗法结合局部阻滞治疗陈旧性半月板损伤55例,取得了较为理想的效果,现报告如下.     

Application of Everolimus in Preoperative Neoadjuvant Therapy of Tuberous Sclerosis Complex Associated With Renal Angiomyolipoma: A Single-Center Report of 5 Cases

BackgroundThe purpose of the study was to investigate the efficacy and safety of everolimus in preoperative neoadjuvant therapy of tuberous sclerosis complex (TSC) associated with renal angiomyolipoma (RAML).Patients and MethodsThe clinical data of 5 patients with TSC associated with RAML who were admitted to our hospital from May 2014 to December 2017 were analyzed. All patients received once per day everolimus 10 mg oral treatment for 3 months, and the efficacy and safety were evaluated at 1 month and 3 months after drug treatment, respectively. All patients received partial nephrectomy (PN) 1 week after drug withdrawal.ResultsAfter 1 month of treatment with everolimus, the median greatest tumor diameter (GTD) decrease was 1.8 cm (range, 1.0-4.5 cm). After 3 months of treatment, the median GTD reduction was 2.5 cm (range, 1.0-5.0 cm). The main adverse reactions included oral mucositis in 4 cases, menstrual disorder in 2 cases, and urinary tract infection in 1 case. The median surgery time was 110 minutes (range, 80-130 minutes), the median intraoperative blood loss was 70 mL (range, 50-400 mL), and the median postoperative hospital stay was 6 days (range, 5-7 days). After a median follow-up of 24 months (range, 6-30 months), no tumor with a diameter of >4 cm was found except for 1 recurrence.ConclusionThe preservation of renal function is the most important thing for patients with TSC associated with bilateral RAML. For some patients who cannot receive PN, neoadjuvant therapy with everolimus might be considered before the surgery so as to give patients the chance of PN.     

Respirator usage protects brain white matter from welding fume exposure: A pilot magnetic resonance imaging study of welders

Welding fume exposure has been associated with structural brain changes and a wide variety of clinical and sub-clinical outcomes including cognitive, behavioral and motor abnormalities. Respirator use has been shown to decrease exposure to welding fumes; however, the associations between respirator use and health outcomes, particularly neurologic health, have been understudied. In this preliminary study, we used diffusion tensor imaging (DTI) to investigate the effectiveness of respirator use in protecting workers’ white matter (WM) from the harmful effects related to welding fume exposure. Fractional anisotropy (FA), a common DTI measurement of water diffusion properties, was used as a marker of WM microstructure integrity. We hypothesized that FA in brain regions involved in motor and neurocognitive functions would differ between welders reporting respirator use compared to those not using a respirator. We enrolled a pilot cohort of 19 welders from labor unions in the New York City area. All welders completed questionnaires to assess welding history and occupational health. All completed a DTI acquisition on a 3 T Siemens scanner. Partial least squares discriminant analysis (PLS-DA), a bioinformatic analytical strategy, was used to model the divergence of WM microstructures in 48 regions defined by the ICBM-DTI-81 atlas between respirator users compared to non-users. This yielded an effective discrimination of respirator users from non-users, with the uncinate fasciculus, the cerebellar peduncle and the superior longitudinal fasciculus contributing most to the discrimination of these groups. These white matter tracts are involved in widespread motor and cognitive functions. To our knowledge, this study is the first to suggest a protective effect of respirator on WM microstructure, indicating that the lack of respirator may present unsafe working conditions for welders. These preliminary findings may inform a larger, longitudinal intervention study that would be more appropriate to investigate the potential protective effect of respirator usage on brain white matter in welders.     

Aripiprazole (Abilify™) Overdose in a Child

Aripiprazole, 7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl] butyloxy}-3,4-dihydro-2(1H)-quinolinone, is an atypical antipsychotic medication inaugurating the newest class of atypical antipsychotics: the partial dopamine agonist. It has a particularly long half-life of elimination and variable metabolism secondary to genetic polymorphism. We report an unintentional overdose of 195 mg (17.1 mg/kg) of aripiprazole in a 2.5 year-old child. This patient exhibited CNS depression not requiring respiratory support and without significant cardiovascular effects. CNS effects persisted for almost 2 weeks postingestion.     

Clinical Significance of Downstaging in Patients With Limited-Disease Small-Cell Lung Cancer

BackgroundWe investigated the effect of downstaging on OS in LD-SCLC patients treated with first-line treatment.Patients and MethodsWe retrospectively reviewed 210 LD-SCLC patients who were treated with first-line treatment at Seoul National University Hospital between April 1999 and November 2012. Compared with initial tumor, node, metastases (TNM) stage, cases that showed a lower TNM stage after treatment were defined as ‘downstaging.’ The relationship between downstaging and OS was analyzed, and a subgroup analysis on the responders was performed.ResultsAfter first-line treatment, 78 (37.1%) patients achieved complete response, 97 (46.2%) achieved PR, and 35 (16.7%) experienced stable disease or progressive disease. A hundred and fifty one patients (71.9%) showed downstaging of their diseases, and the remaining 59 patients (28.1%) showed no change or upstaging. The median OS for patients achieving downstaging and no change/upstaging were 32.8 months and 13.1 months, respectively (P < .001). Of the 97 patients who achieved PR, the OS was significantly longer in patients who showed downstaging than those who did not (25.8 months vs. 13.8 months, respectively; P = .004). In multivariate analyses, female sex, downstaging, lower initial TNM stage, and prophylactic cranial irradiation were independent good prognostic factors for OS.ConclusionDownstaging might be an independent good prognostic factor in LD-SCLC. Specifically, downstaging is expected to be useful for stratification of patients achieving PR. Further prospective studies are warranted to verify whether patients who achieved PR without downstaging can be candidates for consolidation treatments after first-line treatment.