前牙区不翻瓣即刻牙种植术后软硬组织变化的研究

目的:评测前牙区不翻瓣即刻牙种植的近期临床效果及软硬组织变化。方法:2008-07—2012-11于同济大学附属口腔医院种植科就诊的患者中,选择上颌前牙无法保留,适合采取即刻不翻瓣种植的患者纳入实验。于术中,术后3个月、6个月分别测量缺失牙近、远中骨高度及牙龈乳头的高度。结果:共18例患者22颗患牙纳入本研究。X线结果表明种植体均形成良好骨结合。种植后3个月,牙槽骨唇颊侧骨板近、远中吸收分别为(0.47±0.03)mm和(0.56±0.06)mm;6个月时骨吸收分别为(1.60±0.05)mm和(1.73±0.04)mm。种植3个月时,近、远中牙龈附着退缩为(0.41±0.05)mm和(0.53±0.03)mm,6个月牙龈时附着退缩分别为(0.51±0.03)mm和(0.62±0.04)mm。结论:前牙区不翻瓣即刻牙种植能良好地保存种植体周围骨组织及软组织高度,在选择合适适应证的条件下,能在减少手术创伤的基础上获得良好的修复效果。     

Amyloid-β Induces Hepatic Insulin Resistance In Vivo via JAK2

Amyloid-β (Aβ), a natural product of cell metabolism, plays a key role in the pathogenesis of Alzheimer’s disease (AD). Epidemiological studies indicate patients with AD have an increased risk of developing type 2 diabetes mellitus (T2DM). Aβ can induce insulin resistance in cultured hepatocytes by activating the JAK2/STAT3/SOCS-1 signaling pathway. Amyloid precursor protein and presenilin 1 double-transgenic AD mouse models with increased circulating Aβ level show impaired glucose/insulin tolerance and hepatic insulin resistance. However, whether Aβ induces hepatic insulin resistance in vivo is still unclear. Here we show C57BL/6J mice intraperitoneally injected with Aβ42 exhibit increased fasting blood glucose level, impaired insulin tolerance, and hepatic insulin signaling. Moreover, the APPswe/PSEN1dE9 AD model mice intraperitoneally injected with anti-Aβ neutralizing antibodies show decreased fasting blood glucose level and improved insulin sensitivity. Injection of Aβ42 activates hepatic JAK2/STAT3/SOCS-1 signaling, and neutralization of Aβ in APPswe/PSEN1dE9 mice inhibits liver JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by tail vein injection of adenovirus inhibits JAK2/STAT3/SOCS-1 signaling and improves glucose/insulin tolerance and hepatic insulin sensitivity in APPswe/PSEN1dE9 mice. Our results demonstrate that Aβ induces hepatic insulin resistance in vivo via JAK2, suggesting that inhibition of Aβ signaling is a new strategy toward resolving insulin resistance and T2DM.More than 250 million people worldwide were diagnosed with type 2 diabetes mellitus (T2DM) in 2011, and this number is expected to double within the next 20 years (1). Insulin resistance is a key element in the pathogenesis of T2DM, defined as a state of reduced responsiveness to normal circulating levels of insulin in insulin-target liver, skeletal muscle, and adipose tissues (2). Many states give rise to insulin resistance, and all are explained by numerous mechanisms in which insulin signaling is decreased (3). Interestingly, it has been reported that brains from Alzheimer’s disease (AD) patients display impaired insulin signaling (4,5), and some AD patients exhibit impaired glucose metabolism and hyperinsulinemia (6,7). Furthermore, an epidemiological study indicates patients with AD have an increased risk of developing T2DM (8), and experimental studies demonstrate AD model mice also exhibit diabetic phenotype (9,10). These studies together reveal a strong correlation between AD and insulin resistance/T2DM.Amyloid-β (Aβ) is a natural product during cell metabolism and originates from proteolysis of the amyloid precursor protein (APP) by the sequential enzymatic actions of β-site amyloid precursor protein–cleaving enzyme 1 (BACE-1) and γ-secretase (11). According to the amyloid cascade hypothesis, Aβ has an early and vital role in the pathogenesis of AD (11,12). In the central nervous system, Aβ has been reported to impair neuronal synaptic function in early AD by compromising insulin signaling (13–16). Interestingly, Aβ can be detected in the peripheral circulation and tissues (17–19).We have previously reported that Aβ induces insulin resistance in cultured hepatocytes mainly through the JAK2/STAT3/SOCS-1 signaling pathway (10), indicating that Aβ is an inducer of insulin resistance in vitro. On the other hand, animal studies demonstrate that the crossbred mice of APP23 transgenic AD model mice and ob/ob mice showed an accelerated diabetic phenotype (20). Moreover, APPswe/PS1^(A246E) transgenic AD model mice with increased plasma Aβ42 level exhibit impaired glucose tolerance when fed a chow diet (9,21). Consistently, we have recently reported that APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice with increased plasma Aβ40/42 levels show impaired glucose/insulin tolerance and hepatic insulin signaling, hyperinsulinemia, and upregulation of SOCS-1 and phosphorylated JAK2 and STAT3 in the liver (10). However, it is still possible that the insulin resistance in AD model mice might be due to the overexpression of presenilin 1, APP, and/or APP cleavage products except Aβ. Thus, whether Aβ itself can induce insulin resistance in vivo is yet to be elucidated. In addition, we previously showed that Aβ induces insulin resistance by activating the JAK2/STAT3/SOCS-1 signaling pathway in cultured hepatocytes (10). Whether Aβ also induces hepatic insulin resistance in vivo by activating the JAK2/STAT3/SOCS-1 signaling pathway is still unclear.In this study, we investigated the effect of Aβ on insulin sensitivity in vivo by injection of Aβ42 into wild-type mice and injection of Aβ-neutralizing antibodies or adenovirus expressing JAK2 small interfering (si)RNA into APP/PS1 AD model mice. We found that injection of Aβ42 into C57BL/6J mice induces insulin resistance and activates hepatic JAK2/STAT3/SOCS-1 signaling. Moreover, APP/PS1 mice treated with anti–Aβ-neutralizing antibodies show improved insulin sensitivity and attenuated hepatic JAK2/STAT3/SOCS-1 signaling. Furthermore, knockdown of hepatic JAK2 by adenovirus inhibited JAK2/STAT3/SOCS-1 signaling and improved insulin sensitivity in APP/PS1 mice.     

Risk assessment of excess drug and sunscreen absorption via skin with ablative fractional laser resurfacing

The ablative fractional laser is a new modality used for surgical resurfacing. It is expected that laser treatment can generally deliver drugs into and across the skin, which is toxicologically relevant. The aim of this study was to establish skin absorption characteristics of antibiotics, sunscreens, and macromolecules via laser-treated skin and during postoperative periods. Nude mice were employed as the animal model. The skin received a single irradiation of a fractional CO₂ laser, using fluences of 4–10 mJ with spot densities of 100–400 spots/cm². In vitro skin permeation using Franz cells was performed. Levels of skin water loss and erythema were evaluated, and histological examinations with staining by hematoxylin and eosin, cyclooxygenase-2, and claudin-1 were carried out. Significant signs of erythema, edema, and scaling of the skin treated with the fractional laser were evident. Inflammatory infiltration and a reduction in tight junctions were also observed. Laser treatment at 6 mJ increased tetracycline and tretinoin fluxes by 70- and 9-fold, respectively. A higher fluence resulted in a greater tetracycline flux, but lower skin deposition. On the other hand, tretinoin skin deposition increased following an increase in the laser fluence. The fractional laser exhibited a negligible effect on modulating oxybenzone absorption. Dextrans with molecular weights of 4 and 10 kDa showed increased fluxes from 0.05 to 11.05 and 38.54 μg/cm²/h, respectively. The optimized drug dose for skin treated with the fractional laser was 1/70–1/60 of the regular dose. The skin histology and drug absorption had recovered to a normal status within 2–3 days. Our findings provide the first report on risk assessment of excessive skin absorption after fractional laser resurfacing.     

Use of a 'microecological technique' to study crime incidents around methadone maintenance treatment centers

Aims Concern about crime is a significant barrier to the establishment of methadone treatment centers (MTCs). Methadone maintenance reduces crime among those treated, but the relationship between MTCs and neighborhood crime is unknown. We evaluated crime around MTCs. Setting Baltimore City, MD, USA. Participants We evaluated crime around 13 MTCs and three types of control locations: 13 convenience stores (stores), 13 residential points and 10 general medical hospitals. Measures We collected reports of Part 1 crimes from 1 January 1999 to 31 December 2001 from the Baltimore City Police Department. Design Crimes and residential point locations were mapped electronically by street address (geocoded), and MTCs, hospitals and stores were mapped by visiting the sites with a global positioning satellite (GPS) locator. Concentric circular ‘buffers’ were drawn at 25‐m intervals up to 300 m around each site. We used Poisson regression to assess the relationship between crime counts (incidents per unit area) and distance from the site. Findings There was no significant geographic relationship between crime counts and MTCs or hospitals. A significant negative relationship (parameter estimate ?0.3127, P < 0.04) existed around stores in the daytime (7 am–7 pm), indicating higher crime counts closer to the stores. We found a significant positive relationship around residential points during daytime (0.5180, P < 0.0001) and at night (0.3303, P < 0.0001), indicating higher crime counts further away. Conclusions Methadone treatment centers, in contrast to convenience stores, are not associated geographically with crime.     

高糖对小鼠足细胞表型转化的诱导作用及机制探讨

目的观察高糖对小鼠足细胞表型转化的诱导作用,并探讨其机制。方法将传代培养后的小鼠足细胞随机分为A、B、C三组,A组常规培养,B组加入终浓度为30 mmol/L的葡萄糖、C组加入终浓度为30 mmol/L的葡萄糖及10μmol/L的蛋白质酪氨酸激酶(JAK2)特异性阻断剂α-氰-(3,4-二羟基)-N-苄基肉桂酰胺(AG490)进行培养,48 h后收集细胞,采用Western blot法检测足细胞中自身标志物人肾病蛋白(Nephrin)、间充质细胞标志物α-平滑肌肌动蛋白(α-SMA)及磷酸化蛋白质酪氨酸激酶(p-JAK2)蛋白,采用RT-PCR检测足细胞中的Nephrin、α-SMA mRNA。结果 A组足细胞中Nephrin、α-SMA、p-JAK2蛋白积分光密度值分别为0.96±0.01、0.21±0.02、0.39±0.01,B组分别为0.58±0.01、0.66±0.07、0.71±0.02,C组分别为0.87±0.04、0.35±0.02、0.41±0.04;A组足细胞中Nephrin、α-SMA mRNA的相对表达量为1.53±0.04、0.57±0.01,B组分别为0.82±0.09、0.89±0.03,C组分别为1.30±0.04、0.78±0.03。B组与A组比较,P均<0.05;C组与B组比较,P均<0.05。结论高糖可通过激活JAK/STAT信号途径诱导足细胞发生表型转化。     

前白蛋白变化率对肝衰竭预后的预测作用

目的探讨血清前白蛋白(PALB)变化率与肝衰竭预后的关系。方法回顾性分析98例肝衰竭患者的临床资料,对患者进行Child-Pugh分级,并把患者分为好转组与未愈组,收集住院期间初始及末次PALB及其他主要肝功能指标的数值,并计算出PALB及其他主要肝功能指标的变化率。结果入院时患者的初始PALB数值明显下降,且Child-Pugh分级越高,数值越低。好转组与未愈组患者的初始PALB数值相近,当血清PALB数值快速升高时,好转组人数明显多于未愈组;当数值下降时,好转组人数明显少于未愈组;当数值升高不明显时,未愈组与好转组差异无统计学意义,但未愈组人数要多于好转组。PALB变化率的敏感度最高,特异度较总胆红素、凝血酶原活动度、国际标准化比值变化率低,而ROC曲线下面积最大。结论肝衰竭患者初始PALB明显比正常值低,而且病情越重,血清中PALB数值越低,但患者预后与初始PALB无相关性,而与PALB变化率相关。大部分PALB快速升高者,预后好;大部分PALB下降或升高缓慢者,预后差。而且PALB变化率对于预后的预测价值要高于其他主要肝功能指标。     

非淤胆型婴儿巨细胞病毒性肝炎治疗68例

目的:探讨非淤胆型婴儿巨细胞病毒性肝炎的治疗方法.方法:选择2008-01/2010-07本院儿科住院的68例非淤胆型婴儿巨细胞病毒性肝炎患儿,随机分为治疗组34例和对照组34例,均予复方甘草酸苷2 mL/(kg.次),1次/d,共3 wk.治疗组加用更昔洛韦5 mg/(kg.次),2次/d,2 wk;1次/d,1 wk.结果:治疗组和对照组总有效率分别为94.1%和91.1%,治疗3 wk复查肝功能指标结果提示丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(total bilirubin,T B I L)、谷氨酰转肽酶(g a m m a g l u t a m y ltranspeptidase,GGT)和碱性磷酸酶(alkalinephosphatase,ALP)指标较治疗前均明显下降,差异有显著意义(P<0.05);直接胆红素(directbilirubin,DBIL)、总胆汁酸(total bile acid,TBA)指标较治疗前均无明显变化,差异无显著意义(P>0.05).治疗前或治疗后2组间比较上述指标差异无显著意义(P>0.05).随访1年,失访5人,余患儿肝功能均正常;尿CMV-DNA,治疗组18人(54.5%)阳性,对照组15人(50.0%)阳性,差异无显著意义(P>0.05).结论:非淤胆型婴儿巨细胞病毒性肝炎不建议常规予更昔洛韦抗病毒治疗.     

TEAS复合药物全麻行控制性降压后胃血流的变化

目的:探讨经皮穴位电刺激(transcutaneous electrical acupoint stimulation,TEAS)复合药物全麻行控制性降压至不同血压水平的胃血流变化,从而明确针药复合麻醉的胃保护机制.方法:54只,♂,比格犬随机分为9组:单纯全麻组、60%对照组、60%实验组、50%对照组、50%实验组、40%对照组、40%实验组、30%对照组、30%实验组,每组6只,后8组动物均以异氟醚联合硝普钠行控制性降压,将动脉血压降至60%、50%、40%、30%基础平均动脉血压水平并维持60min,单纯全麻组不行控制性降压.实验组采用TEAS干预处理,采用激光多普勒组织血流仪监测不同水平相应时间点胃表面血流的变化.结果:在行控制性降压至目标低血压水平(T0)时,所有对照组胃血流均显著低于各自基础水平(P<0.05),而60%实验组、50%实验组胃血流未明显降低,在维持10min(T1)时,除50%实验组外,其他各控压组胃血流均显著低于各自基础水平和同期单纯全麻组水平(P<0.05),50%实验组与同水平对照组相比有显著统计学差异(P<0.05),在血压回升阶段,50%、30%、40%实验组胃血流先后恢复至基础水平和同期单纯全麻组水平,而同水平对照组未明显恢复.结论:轻度控压时(尤其是50%水平),TEAS的胃保护效应明显.重度控压时(尤其是30%水平),TEAS基本无保护效应,但在血压回升结束时,TEAS可促进胃血流的较快恢复.