RB1 dual role in proliferation and apoptosis: Cell fate control and implications for cancer therapy

Inactivation of the retinoblastoma (RB1) tumor suppressor is one of the most frequent and early recognized molecular hallmarks of cancer. RB1, although mainly studied for its role in the regulation of cell cycle, emerged as a key regulator of many biological processes. Among these, RB1 has been implicated in the regulation of apoptosis, the alteration of which underlies both cancer development and resistance to therapy. RB1 role in apoptosis, however, is still controversial because, depending on the context, the apoptotic cues, and its own status, RB1 can act either by inhibiting or promoting apoptosis. Moreover, the mechanisms whereby RB1 controls both proliferation and apoptosis in a coordinated manner are only now beginning to be unraveled. Here, by reviewing the main studies assessing the effect of RB1 status and modulation on these processes, we provide an overview of the possible underlying molecular mechanisms whereby RB1, and its family members, dictate cell fate in various contexts. We also describe the current antitumoral strategies aimed at the use of RB1 as predictive, prognostic and therapeutic target in cancer. A thorough understanding of RB1 function in controlling cell fate determination is crucial for a successful translation of RB1 status assessment in the clinical setting.     

Co-expression of CXCL8 and HIF-1α is associated with metastasis and poor prognosis in hepatocellular carcinoma

Hypoxia inducible factor-1α (HIF-1α), induces cytokines such as CXCL8 and tumor dissemination, chemo- and radio-resistance. We analyzed correlation between HIF-1α and CXCL8 levels, tumor characteristics and overall survival in 102 hepatocellular carcinoma (HCC) patients. Levels of HIF-1α and CXCL8 were increased in HCC tissues and cell lines. Patients with high levels of HIF-1α and CXCL8 had worse outcome and poorer prognosis than those with lower levels. Co-overexpression of HIF-1α and CXCL8 was an independent negative prognostic factor for overall and disease-free survival. HIF-1α silencing and CXCL8 siRNA decreased migration under hypoxic conditions in vitro. Hypoxia-induced activation of AKT/mTOR/STAT3 pathways was reversed by depletion of CXCL8. We conclude that HIF-1α and CXCL8 induce HCC progression and metastasis, associated with activation of AKT/mTOR/STAT3. Co-expression of HIF-1α and CXCL8 is a prognostic marker and a potential therapeutic target in HCC.     

柠檬酸碳酸氢盐透析液安全性评估及其对淋巴细胞亚群的影响

目的 研究柠檬酸碳酸氢盐透析液的安全性及其对维持性血液透析（MHD）患者外周血淋巴细胞亚群（CD4^＋、CD8^＋）和HLA-DR的影响。方法 选择西安交通大学第二医院肾内科30例2HD患者进行前后自身对照，前4周使用常规碳酸氢盐透析液（对照组），后4周使用柠檬酸酸碳酸氢盐透析液（实验组）。观察患者首次透析过程中生命体征。测定实验组首次透析前、透析后、透析后1h及第4周透析后1h血清离子钙（iCa^2＋）和柠檬酸的水平。两组首次透析前和第4周透析结束时分别测定CD4^＋、CD8^＋和HLA-DR表达率。结果 两组透析过程中生命体征平稳；实验组血清柠檬酸透析前后基本保持不变，iCa^2＋在透析后明显增高（P〈0．05）；两组透析后外周血淋巴细胞亚群（CD4^＋／CD8^＋比值）活性均增高，但对照组以CD4^＋升高为主，实验组以CD8^＋降低为主；HLA-DR在实验组透析后明显升高（P〈0．05），而对照组改变不明显。结论 柠檬酸碳酸氢盐透析液有其独特的优点，具有临床推广应用的价值。     

Glutamate neurons in the substantia nigra compacta and retrorubral field

Dopaminergic neurons of the substantia nigra compacta (SNC), ventral tegmental area (VTA) and retrorubral field (RRF) play a role in reward, motivation, learning, memory, and movement. These neurons are intermingled with GABAergic neurons. Recent evidence shows that the VTA contains glutamatergic neurons expressing vesicular glutamate transporter type 2 (VGluT2); some of them co‐express tyrosine hydroxylase (TH). Here, we used a combination of radioactive in situ hybridisation and immunohistochemistry to explore whether any of the vesicular glutamate transporters [vesicular glutamate transporter type 1 (VGluT1), VGluT2, or vesicular glutamate transporter type 3 (VGluT3)] were encoded by neurons in the SNC or RRF. We found expression of VGluT2 mRNA, but not of VGluT1 or VGluT3, in the SNC and RRF. These VGluT2 neurons rarely showed TH immunoreactivity. Within the SNC, the VGluT2 neurons were infrequently found at the rostral level, but were often seen at the medial and caudal levels intercalated in the mediolateral portion of the dorsal tier, at a ratio of one VGluT2 neuron per 4.4 TH neurons. At this level, VGluT2 neurons were also found in the adjacent substantia nigra reticulata and substantia nigra pars lateralis. Within the RRF, the VGluT2 neurons showed an increasing rostrocaudal gradient of distribution. The RRF proportion of VGluT2 neurons in relation to TH neurons was constant throughout the rostrocaudal levels, showing an average ratio of one VGluT2 neuron per 1.7 TH neurons. In summary, we provide evidence indicating that the SNC and RRF, which are traditionally considered to be dopaminergic areas, have neurons with the ability to participate in glutamate signaling.     

牙槽突裂植骨前后上颌扩弓对上颌牙槽骨位移影响的三维有限元分析

目的模拟比较牙槽突裂植骨前后上颌扩弓对上颌牙槽骨位移影响。方法在已建立的植骨前上颌骨有限元模型上，采用ANSYS软件模拟牙槽突裂植骨，形成植骨后上颌骨模型。在2组模型上分别施加相同上颌扩弓力，观察比较牙槽骨区域三维方向位移形变情况。结果三维方向位移量比较，植骨前扩弓组均显著大于植骨后扩弓组（P<0.05）。水平向位移：植骨前扩弓，由前向后牙槽骨区域位移量逐渐降低；植骨后扩弓，由前向后牙槽骨区域位移量逐渐升高；植骨前后扩弓健侧牙槽骨位移量均显著大于患侧（P<0.05）。垂直向位移：植骨前后扩弓，牙槽骨前内侧均向下移动，牙槽骨后外侧均向上移动。矢状向位移：植骨前扩弓，牙槽骨前内侧向前移动，后外侧向后移动，植骨后扩弓移动趋势相反。结论单侧完全性唇腭裂患者植骨前扩弓三维方向移动均较植骨后明显，植骨前扩弓建议扩弓器适当向后移动，植骨后扩弓建议扩弓器适当向前移动并配合前牵引治疗，同时治疗中需警惕不对称扩弓及前牙开的发生。     

核饰瓷厚度和树脂水门汀对玻璃陶瓷贴面乳光性能的影响

目的分析不同瓷层厚度和树脂水门汀对玻璃陶瓷贴面修复变色牙乳光性能的影响。方法采用计算机辅助设计与计算机辅助制造（CAD/CAM）工艺制作IPS e.max CAD LT A3瓷贴面试件，核瓷组厚度分别为0.25 mm和0.50 mm；核瓷/饰瓷组厚度为0.25 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.50 mm牙本质瓷和0.50 mm核瓷/0.25 mm牙本质瓷/0.25 mm切端瓷。模拟瓷贴面临床粘接程序，在CAD/CAM瓷贴面试件底部涂布Variolink N Bleach XL水门汀，制作CAD/CAM瓷贴面-树脂水门汀复合试件。利用分光光度计测试试件在反射和透射模式下色度值，并计算乳光值。结果0.25 mm、0.50 mm核瓷组和0.25 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.50 mm牙本质瓷、0.50 mm核瓷/0.25 mm牙本质瓷/0.25 mm切端瓷瓷贴面试件乳光值分别为6.10±0.50、7.00±0.24、6.40±0.24、7.08±0.28、7.16±0.21、7.81±0.11。随着核瓷厚度增加，乳光值显著增大（P<0.05）；核瓷厚度相同，增加0.25 mm牙本质瓷，乳光值的差异无统计学意义（P>0.05）。对于0.5mm核瓷组，牙本质瓷厚度从0.25 mm增加至0.5 mm，乳光值差异无统计学意义（P>0.05），但增加0.25 mm切端瓷后乳光值显著增大（P<0.05）。0.25 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.25 mm牙本质瓷、0.50 mm核瓷/0.50 mm牙本质瓷和0.50 mm核瓷/0.25 mm牙本质瓷/0.25 mm切端瓷CAD/CAM瓷贴面-树脂水门汀复合体试件的乳光值分别为6.29±0.31、7.56±0.36、7.67±0.30、8.65±0.53，随瓷层厚度增加乳光值增大（P<0.05），但0.50 mm核瓷/0.25 mm牙本质瓷和0.50 mm核瓷/0.50 mm牙本质瓷组间差异无统计学意义（P=0.733）。瓷层厚度和树脂水门汀对试件乳光值的影响均有统计学差异（P<0.05），总厚度与有无树脂水门汀间无交互作用（P>0.05）。结论玻璃陶瓷贴面修复变色牙时，为提高其乳光性能获得自然逼真的修复效果，推荐采用核瓷表面烧结切端瓷的设计，同时可适当增加核瓷厚度，选择具有遮色效果的树脂水门汀。     

2015—2020年河南省儿童第一恒磨牙健康状况调查

目的了解河南省6~9岁儿童第一恒磨牙萌出、患龋及窝沟封闭等情况。方法对中国儿童口腔疾病综合干预项目信息管理系统中2015—2020年河南省口腔健康检查数据进行分析。结果河南486 865名儿童中，6~9岁儿童4颗第一恒磨牙均完全萌出率为73.44%，患龋率30.35%，龋均（0.67±1.18）颗，龋补充填比4.45%，窝沟封闭率2.36%。2015—2020年，6、7、8岁儿童4颗第一恒磨牙均完全萌出率都呈下降趋势（χ²_趋分别为385.793、964.142、71.964，P<0.05），而6~9岁儿童患龋率、龋均、龋补充填比及窝沟封闭率均呈上升趋势（χ²_趋/F_趋分别为1 115.87、1 270.53、1 215.02、763.48，均P<0.05）。4颗第一恒磨牙均完全萌出率郊县（75.41%）高于城市（71.90%）（χ²=756.44，P<0.05），而患龋率、龋均、龋补充填比及窝沟封闭率城市（34.23%、0.76±1.24、4.99%、3.75%）均高于郊县（25.39%、0.55±1.09、3.50%、0.58%）（χ²分别为4 435.30、3 922.56、390.89、5 262.76，均P<0.05）。上颌第一恒磨牙完全萌出率（84.96%）高于下颌（82.88%）（χ²=1 565.70，P<0.05），龋齿发生率下颌（26.07%）高于上颌（13.88%）（χ²=38 112.53，P<0.05）。结论河南省6~9岁儿童第一恒磨牙健康状况不容乐观，萌出率呈下降趋势，患龋率呈上升趋势，龋补充填率以及窝沟封闭率均较低。这提示人们应关注儿童的饮食习惯和口腔卫生，进一步加强口腔健康教育，提高其口腔保健意识。     

自体牙本质用于牙槽嵴增量的Meta分析

目的通过Meta分析方法系统评估在牙槽嵴缺损需要骨增量时使用自体牙本质（ATD）移植的有效性及安全性。方法电子检索2010年1月1日—2022年3月19日PubMed、Embase、Web of Science、Cochrane Library、CNKI、万方数据库有关牙槽嵴增量使用ATD的临床研究。使用Cochrane Tool评估随机对照试验的偏倚风险，使用Newcastle-Ottawa Scale评估队列研究。RevMan 5.4对数据进行合并分析。结果共纳入10项研究，其中5项研究对照组采用自体骨，另5项研究对照组采用脱蛋白牛骨基质（DBBM）。Meta分析结果显示，牙槽嵴增量术后6个月，ATD较自体骨获得更多水平向牙槽嵴增量［MD=2.01，95%可信区间（CI）（1.09，2.93），P<0.000 1］，但在垂直向牙槽嵴增量上效果相似［MD=−0.06，95%CI（−0.21，0.08），P=0.39］。ATD与自体骨或DBBM相比呈现更少的材料吸收［MD=−0.59，95%CI（−1.03，−0.15），P=0.008；MD=−0.63，95%CI（−1.18，−0.07），P=0.03］，而在种植体稳定系数和术后并发症上均无显著差异［MD=−0.76，95%CI（−3.04，1.52），P=0.51；RR=1.01，95%CI（0.33，3.12），P=0.98］。结论有限证据表明，在牙槽嵴缺损中移植ATD可取得与移植自体骨或DBBM类似或更佳的骨增量效果且材料吸收更少，可作为扩增牙槽嵴的植骨材料。但仍需要进行更大样本、更高质量、更长随访时间的临床试验评估ATD在牙槽嵴增量中的疗效。