Central Regulation of Branched-Chain Amino Acids Is Mediated by AgRP Neurons

Circulating branched-chain amino acids (BCAAs) are elevated in obesity and diabetes, and recent studies support a causal role for BCAAs in insulin resistance and defective glycemic control. The physiological mechanisms underlying BCAA regulation are poorly understood. Here we show that insulin signaling in the mediobasal hypothalamus (MBH) of rats is mandatory for lowering plasma BCAAs, most probably by inducing hepatic BCAA catabolism. Insulin receptor deletion only in agouti-related protein (AgRP)–expressing neurons (AgRP neurons) in the MBH impaired hepatic BCAA breakdown and suppression of plasma BCAAs during hyperinsulinemic clamps in mice. In support of this, chemogenetic stimulation of AgRP neurons in the absence of food significantly raised plasma BCAAs and impaired hepatic BCAA degradation. A prolonged fasting or ghrelin treatment recapitulated designer receptors exclusively activated by designer drugs–induced activation of AgRP neurons and increased plasma BCAAs. Acute stimulation of vagal motor neurons in the dorsal motor nucleus was sufficient to decrease plasma BCAAs. Notably, elevated plasma BCAAs were associated with impaired glucose homeostasis. These findings suggest a critical role of insulin signaling in AgRP neurons for BCAA regulation and raise the possibility that this control may be mediated primarily via vagal outflow. Furthermore, our results provide an opportunity to closely examine the potential mechanistic link between central nervous system–driven BCAA control and glucose homeostasis.     

Periadventitial dissection of the superior mesenteric artery for locally advanced pancreatic cancer: Surgical planning with the “halo sign” and “string sign”

Most patients diagnosed with pancreatic cancer are classified as nonoperative candidates based on the contemporary guidelines of resectability. The advent of more potent control of systemic disease using neoadjuvant chemotherapy has enabled more aggressive operative interventions. In our multidisciplinary practice, patients with Stage III, locally advanced pancreatic cancer and superior mesenteric artery (SMA) encasement are now carefully triaged with high quality, preoperative imaging to determine if they can be considered candidates for operative resection with periadventitial dissection of the SMA. Patients displaying a “halo sign,” where the encased SMA remains fully patent and free from arterial invasion, are now candidates for SMA periadventitial dissection. This procedure involves the surgical stripping of the infiltrated neurolymphatic tissue off the SMA leaving behind a bare “skeletonized artery.” Alternatively, the “string sign” involving the SMA confers a more likely case of arterial invasion, where a complete oncologic resection cannot be achieved successfully. This method of patient selection in case of SMA involvement abandons the traditional metrics of circumferential degrees of the arterial encasement to guide surgical decisions. Our institutional approach has allowed us to meaningfully expand our operative methods of resection with the potential for improved longitudinal outcomes to pancreatic cancer patients who were deprived historically from the more effective and possibly curative treatment.     

“治未病”思想在慢性便秘防治实践中的应用

“治未病”思想是中医学的重要组成部分,其核心思想分为3个方面:“未生先防”强调防患于未然,避免疾病的发生;“未盛防变”强调已病早治,防止其进展及传变,避免其他脏腑受累;“已衰防复”强调在疾病初愈之时,注意调摄,以防疾病复发。“治未病”思想在慢性便秘防治中发挥了重要作用,通过多样的手段干预慢性便秘患者各个病程阶段,对改善患者生命质量具有重要意义。     

青黛表面改性对口腔溃疡双层膜质量与药效的影响

目的 采用溶剂浇铸法制备口腔溃疡双层膜剂,研究青黛表面改性前后对膜剂质量与药效的影响。方法 通过单因素实验设计和响应面优化法优选膜剂最佳处方,并对膜剂表面形貌、黏附时间、抗拉强度、含量测定以及体外药物释放等性能进行评估。进一步采用化学灼烧法建立大鼠口腔溃疡模型,考察膜剂对溃疡组织肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）、白细胞介素-1β（interleukin-1β,IL-1β）、IL-6以及口腔溃疡组织形态的影响。结果 空白隔离层确定为25 mg/mL的乙基纤维素乙醇溶液,载药膜最佳处方为63 mg/mL PVA17-88、55 mg/mL PVP K30、3.0 mg/mL明胶与0.047 mL/mL甘油。青黛表面改性后,双层膜剂比未改性双层膜剂具有更加光滑均一的外观、更高的含量均匀性和有效成分靛蓝释放率。药效学结果表明,与模型组相比,阳性组与青黛改性膜剂组显著降低了溃疡组织TNF-α、IL-1β、IL-6的含量（P＜0.05）,并减少了炎症细胞的浸润,溃疡组织愈合程度较高。结论 青黛改性之后的口腔溃疡双层膜剂具有更好的质量与更佳的疗效,具有较好的应用前景。     

李彦民治疗类风湿关节炎经验

类风湿关节炎(RA)在中医学中属于“痹病”范畴,是临床中常见的难治性疾病,且呈年轻化趋势,迁延难愈。目前现代医学对RA的发病病因及机制尚不完全清楚。《素问·痹论》提出风寒湿三邪致痹,还有学者提出痰瘀致痹、肝肾亏虚等观点。李彦民主任医师根据多年临床经验提出RA的病机关键是络脉痹阻,其病机特点是虚实夹杂,临床辨证分为寒湿阻络型、湿热蕴结型、痰瘀互结型、气血两虚型、肝肾亏虚型等五型。分别采用祛邪通络和补虚通络等不同治则,辨证施法。李老师善用川乌、鸡血藤以及乌梢蛇等药以通络止痛,并主张辨证用药,内外兼治,多取良效。临床采用经验方仙龙汤,配合外用舒筋活络洗剂,且取得理想疗效。     

双相生物钙磷陶瓷生物相容性及异位骨诱导的实验研究

目的检测运用羟基磷灰石及β-磷酸三钙制备的双相钙磷陶瓷的生物相容性及其异位骨诱导效率。方法采用化学共沉淀法及过氧化氢发泡法,将羟基磷灰石及β-磷酸三钙以6∶4的比例在1 100 ℃条件下烧结3 h获得双相钙磷陶瓷,利用X线衍射评估材料组成成分。分离SD大鼠骨髓间充质干细胞,接种于双相钙磷陶瓷,通过扫描电镜、鬼笔环肽及DAPI染色观察细胞的黏附,CCK8法评估细胞增殖,碱性磷酸酶测定法评估骨髓间充质干细胞的碱性磷酸酶表达活性。将不含骨髓间充质干细胞的双相钙磷陶瓷置入比格犬竖脊肌内,于4、8、12周对样本行大体检测、组织染色,测算新骨生成率,从而评估双相钙磷陶瓷的异位骨诱导效率。结果成功制备双相钙磷陶瓷,X线衍射分析可见羟基磷灰石及β-磷酸三钙特异性的衍射峰。扫描电镜可见双相钙磷陶瓷表面广泛分布大孔及连通孔,孔壁粗糙不平,孔内可见均匀分布的微孔。鬼笔环肽及DAPI染色显示,骨髓充质干细胞在材料表面伸展黏附,共培养后逐渐从不规则形转变为均一的长梭形。CCK8法提示共培养后第1天,细胞活力降低,而第3、4、5、7天,细胞增殖活力逐渐增加。碱性磷酸酶活性检测提示,与对照组相比,共培养后第1、7天,双相钙磷陶瓷组的骨髓间充质干细胞可分泌更多的碱性磷酸酶。双相钙磷陶瓷顺利置入比格犬竖脊肌内,术后8周材料孔隙内可见骨样组织沉积,术后12周大孔成骨比例为0.77±0.11,孔内成骨面积比例为0.71±0.14。结论双相钙磷陶瓷具有良好的生物相容性及异位骨诱导效率。