Bond durability when applying phosphate ester monomer–containing primers vs. self-adhesive resin cements to zirconia: Evaluation after different aging conditions

PurposeThis study aimed to evaluate bond durability when applying 2 phosphate ester monomer-containing self-adhesive resin cements alone, versus a combination of phosphate ester monomer-containing primer conditioning plus 2 conventional resin cements requiring primers, to zirconia after different artificial aging methods.MethodsWe cemented air-abraded zirconia plates to composite resin cylinders with self-adhesive resin cements (MS; RU) alone or cemented them with traditional resin cements (ZRV; ZVN) after pre-conditioning with a zirconia primer. A shear bond strength (SBS) test were performed after subjecting them to 19 different aging conditions (n = 15) comprising 30,000× thermocycles, air storage at room temperature (RT), water storage at RT, or at 37 °C for 24 h, 1 week, 1, 3, 6, and 12 months. Zirconia powders mixed with zirconia primer or 2 self-adhesive resin cements were characterized by X-ray photoelectron spectroscopy.ResultsGroups MS and ZVN obtained the highest SBS after all of aging methods. SBS after 6 months of storage was similar to SBS after 24 h of storage, while both were higher than SBS after 1 year of storage. Water storage at 37 °C provided higher SBS than RT water storage did. We detected a Zr–O–P bond in both self-adhesive resin cement/zirconia powder mixtures.ConclusionsApplication of self-adhesive resin cements alone could be an alternative to pre-conditioning with a zirconia primer followed by the application of conventional resin cements. Formation of Zr–O–P bonds contributed to the bonding improvement of self-adhesive resin cements. Different aging conditions affected SBS values.     

黏膜下注射不同剂量地塞米松改善下颌第三磨牙拔除术后症状的疗效观察

目的研究不同剂量地塞米松黏膜下注射对下颌第三磨牙拔除术后症状的临床疗效。方法选取2016年8月—2016年11月复旦大学附属中山医院和上海市静安区牙病防治所收治的拔除下颌第三磨牙患者156例,随机分为对照组(53例)、地塞米松4 mg组(51例)和地塞米松8 mg组(52例)。对照组术前于下颌第三磨牙黏膜周围1 cm范围内注射生理盐水。地塞米松4 mg组术前于下颌第三磨牙黏膜周围1 cm范围内注射地塞米松磷酸钠注射液4 mg。地塞米松8 mg组术前于下颌第三磨牙黏膜周围1 cm范围内注射地塞米松磷酸钠注射液8 mg。观察3组的第三磨牙拔除术后症状严重度(Po SSe)量表评分,比较3组的术后肿胀程度和最大张口程度。结果治疗后,地塞米松4 mg组和地塞米松8 mg组饮食、言语、肿胀、疼痛、日常生活评分和总评分明显低于对照组,3组比较差异有统计学意义(P0.05);且地塞米松8 mg组这些观察指标下降程度明显优于地塞米松4 mg组,两组比较差异具有统计学意义(P0.05)。治疗后,地塞米松8 mg组1级肿胀占比明显高于对照组和地塞米松4 mg组,而3、4级肿胀明显低于对照组和地塞米松4 mg组,3组比较差异具有统计学意义(P0.05)。术后1周,地塞米松4 mg组和地塞米松8 mg组最大张口程度明显大于对照组,3组比较差异具有统计学意义(P0.05)。结论黏膜下注射地塞米松可改善下颌第三磨牙拔除术后症状,可减少术后肿胀程度,增加术后1周最大张口程度,且地塞米松8 mg优于地塞米松4 mg,具有一定的临床推广应用价值。     

熊去氧胆酸胶囊联合地塞米松治疗老年肝内胆汁淤积性肝炎的疗效观察

目的探讨熊去氧胆酸胶囊联合地塞米松磷酸钠注射液治疗老年肝内胆汁淤积性肝炎的临床疗效。方法选取2014年12月—2016年12月重庆市大足区人民医院收治的老年肝内胆汁淤积性肝炎患者70例,按随机数字法将所有患者分为对照组和治疗组,每组各35例。对照组口服熊去氧胆酸胶囊,1粒/次,3次/d;治疗组在对照组的基础上静脉滴注地塞米松磷酸钠注射液,5 mg加入到10%葡萄糖500 m L中,1次/d。两组连续治疗2周。观察两组的临床疗效,比较两组的肝功能和生活质量评分情况。结果治疗后,对照组和治疗组的总有效率分别为71.43%、94.29%,两组比较差异具有统计学意义(P0.05)。治疗后,两组总胆汁酸(TBA)、直接胆红素(DBIL)、天冬氨酸氨基转氨酶(AST)和丙氨酸氨基转移酶(ALT)均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组腹部症状、全身症状、乏力、活动、焦虑和情感功能评分均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。结论熊去氧胆酸胶囊联合地塞米松磷酸钠注射液治疗老年肝内胆汁淤积性肝炎具有较好的临床效果,可改善肝功能,提高生活质量,安全性较好,具有一定的临床推广应用价值。     

The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy

Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3⁺PD-1⁺ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3⁺PD-1⁺ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.     

Design and synthesis of selective sphingosine-1-phosphate receptor 1 agonists with increased phosphorylation rates

FTY720 and IMMH002, prodrugs for sphingosine-1-phosphate receptor 1 (S1P₁) agonists, show inadequate and inconsistent levels of phosphorylation in humans compared to that in rats. In this study, FTY720 or IMMH002 analogues (21–24) were designed and synthesized with modified head pieces to improve the biotransformation of the prodrugs to the active phosphorylated forms. Target compounds were synthesized via a convergent route using the key and optically pure building block 9, which was first synthesized via asymmetrically catalyzed amination. The phosphorylation rates of these analogues in rat or human blood were compared. The new methyl-substituted analogue compound 21 showed higher phosphorylation rates in both rats and humans than the parent compound, whereas compound 23 showed improvements in rats, but not in humans. In pharmacokinetics studies of rats, compounds 21 and 23 both had higher levels of phosphorylation than FTY720 and IMMH002. Thus, our study not only yielded new compounds with therapeutic potential, but also showed species differences between rats and humans in response to the structural modifications, which might be useful for predicting the biotransformation behavior and efficacy of this class of prodrugs in the clinic.     

磷酸钙作为佐剂应用在乙肝核酸疫苗中的可能性研究

目的：研究使用磷酸钙作为乙ＤＮＡ疫苗的佐剂,诱导机体免疫反应的可能性,方法：磷酸钙与疫苗ＤＮＡ制备出磷酸钙－ＤＮＡ共沉物,免疫小鼠,检测外周血抗体,观察免疫应答反应,结果：磷酸钙－ＤＮＡ共沉物能激发机体免疫应答反应。结论：佐剂在核酸疫苗的应用值得进一步研究。     

高效液相色谱法测定克林霉素磷酸酯片的溶出度

目的:用高效液相色谱法测定克林霉素磷酸酯片的溶出度.方法:采用转篮法测定克林霉素磷酸酯片的溶出度,以高效液相色谱法测定其浓度.色谱柱为RP-C18柱(5μm,200 mm×4.6 mm),流动相为0.1 mol/L磷酸二氢钾溶液-乙腈(775:225),流速为1.0 mL/min,检测波长为210 nm,室温下测定.结果:在0.04～1.00 mg/mL的浓度范围内,线性关系良好(r=0.999 2),平均回收率为100.0%,RSD为0.88%.结论:高效液相色谱法分析速度快,结果准确,适用于克林霉素磷酸酯片溶出度的测定.     

磷酸川芎嗪羧甲基壳聚糖纳米粒的制备及体外释放研究

目的:制备磷酸川芎嗪羧甲基壳聚糖纳米粒(CMC-TMP-NP),并对其体外释放行为进行研究。方法:采用乳化交联法制备CMC-TMP-NP,以包封率为评价指标,通过正交设计实验对处方和工艺进行优化;通过测定CMC-TMP-NP的包封率、载药量、粒径、形态和体外释放率评价其质量。结果:优选出CMC浓度为4mg/mL、投药比为1:2、交联度为3,进行制备CMC-TMP-NP;制备出的纳米粒粒径分布均匀且表面呈圆整球形,平均粒径为192.6nm、多分散系数为0.219、平均包封率为(85.17±1.25)%、平均载药量为(9.38±1.28)%。结论:实验制备的CMC-TMP-NP包封率高,粒径分布均匀,体外能显著延缓药物释放。     

Neurotoxic injury pathways in differentiated mouse motor neuron-neuroblastoma hybrid (NSC-34D) cells in vitro--limited effect of riluzole on thapsigargin, but not staurosporine, hydrogen peroxide and homocysteine neurotoxicity

The neuroblastoma-spinal motor neuron fusion cell line, NSC-34, in its differentiated form, NSC-34D, permits examining the effects of riluzole, a proven treatment for amyotrophic lateral sclerosis (ALS) on cell death induction by staurosporine (STS), thapsigargin (Thaps), hydrogen peroxide (H₂O₂) and homocysteine (HCy). These neurotoxins, applied exogenously, have mechanisms of action related to the various proposed molecular pathogenetic pathways in ALS and are differentiated from endogenous cell death that is associated with cytoplasmic aggregate formation in motor neurons. Nuclear morphology, caspase-3/7 activation and high content imaging were used to assess toxicity of these neurotoxins with and without co-treatment with riluzole, a benzothiazole compound with multiple pharmacological actions. STS was the most potent neurotoxin at killing NSC-34D cells with a toxic concentration at which 50% of maximal cell death is achieved (TC₅₀ = 0.01 μM), followed by Thaps (TC₅₀ = 0.9 μM) and H₂O₂ (TC₅₀ = 15 μM) with HCy requiring higher concentrations to kill at the same level (TC₅₀ = 2200 μM). Riluzole provided neurorescue with a 20% absolute reduction (47.6% relative reduction) in apoptotic cell death against Thaps-induced NSC-34D cell (p ≤ 0.05), but had no effect on STS-, H₂O₂- and HCy-induced NSC-34D cell death. This effect of riluzole on Thaps induction of cell death was independent of caspase-3/7 activation. Riluzole mitigated a toxin that can cause intracellular calcium dysregulation associated with endoplasmic reticulum (ER) stress but not toxins associated with other cell death mechanisms.     

顶空气相色谱法测定双氢青蒿素哌喹片中乙醇残留含量

目的建立双氢青蒿素哌喹片中乙醇残留检测方法。方法采用顶空气相色谱法,色谱柱:HP-Innowax(0.32 mm×30 m,0.5μm),柱温:程序升温,初始温度50℃,保持7 min,以每分钟10℃速率升温至150℃,保持2min;进样口温度180℃,FID检测器温度250℃,正丙醇为内标物,载气为氮气。顶空平衡温度:85℃,平衡时间,25min。结果乙醇、正丙醇分离度良好,乙醇在0.065 07¹.041 2 mg·mL-1范围内线性关系良好(r=0.999 9),平均加样回收率为102.0%,其RSD为2.20%。结论该方法操作简便快速,灵敏度高,准确度好,可作为双氢青蒿素哌喹片中乙醇残留测定。