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ELABELA protects against diabetic kidney disease by activating high glucose-inhibited renal tubular autophagy ELABELA通过激活高葡萄糖抑制的肾小管自噬来预防糖尿病肾病
Pub Date : 2023-01-01 DOI: 10.7555/jbr.36.20220214
Xiyin Zheng, Lulu Yin, Jing Song, Juan Chen, Wensha Gu, Min Shi, Hong Zhang
ELABELA (ELA), an endogenous ligand for the apelin receptor (APJ), has been observed to decrease in the plasma of patients with diabetic kidney disease (DKD). The current study explored potential function and underlying mechanisms of ELA in DKD. Our findings revealed that the ELA levels were decreased in the kidneys of DKD mice. ELA administration mitigated renal damage and downregulated the expression of fibronectin (FN), collagen Ⅳ (Col-Ⅳ), and transforming growth factor-β1 (TGF-β1) in the db/db mice and high glucose cultured HK-2 cells. Furthermore, the autophagy markers, the Beclin-1 and LC3-Ⅱ/Ⅰ ratio, were significantly impaired in DKD, but the ELA treatment reversed these alterations. Mechanistically, the inhibitory effects of ELA on the secretion of fibrosis-associated proteins in high glucose conditions were blocked by pretreatment with 3-methyladenine (3-MA, an autophagy inhibitor). It is likely that ELA protected against renal damage in the db/db mice and high glucose-induced HK-2 cell injury through the activation of renal tubular autophagy. In conclusion, ELA may effectively protect against DKD by activating high glucose-inhibited renal tubular autophagy.
ELABELA (ELA)是一种内源性的APJ受体配体,研究发现糖尿病肾病(DKD)患者血浆中ELABELA (ELA)含量降低。本研究探讨了ELA在DKD中的潜在功能和潜在机制。我们的研究结果显示,DKD小鼠肾脏中的ELA水平降低。ELA减轻了db/db小鼠和高糖培养HK-2细胞中纤维连接蛋白(FN)、胶原Ⅳ(Col-Ⅳ)和转化生长因子-β1 (TGF-β1)的表达。此外,自噬标志物Beclin-1和LC3-Ⅱ/Ⅰ比值在DKD中显著受损,但ELA治疗逆转了这些改变。在机制上,ELA对高糖条件下纤维化相关蛋白分泌的抑制作用被3-甲基腺嘌呤(3-MA,一种自噬抑制剂)预处理阻断。ELA可能通过激活肾小管自噬来保护db/db小鼠的肾损伤和高糖诱导的HK-2细胞损伤。综上所述,ELA可能通过激活高糖抑制的肾小管自噬来有效预防DKD。
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引用次数: 0
Irisin/BDNF signaling in the muscle-brain axis and circadian system: a review 鸢尾素/BDNF信号在肌脑轴和昼夜节律系统中的研究进展
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230133
None Alexey N. Inyushkin, None Vitalii S. Poletaev, None Elena M. Inyushkina, None Igor S. Kalberdin, None Andrey A. Inyushkin
In mammals, the timing of physiological, biochemical and behavioral processes over a 24-h period is controlled by circadian rhythms. To entrain the master clock located in the suprachiasmatic nucleus of the hypothalamus to a precise 24-h rhythm, environmental zeitgebers are used by the circadian system. This is done primarily by signals from the retina via the retinohypothalamic tract, but other cues like exercise, feeding, temperature, anxiety, and social events have also been shown to be non-photic zeitgebers. The recently identified myokine irisin is proposed to serve as an entraining non-photic signal of exercise. Irisin is a product of cleavage and modification from its precursor membrane fibronectin type Ⅲ domain-containing protein 5 (FNDC5) in response to exercise. Apart from well-known peripheral effects, such as the “browning" of white adipocytes, irisin can penetrate the blood-brain barrier and display the effects on the brain. Experimental data suggest that FNDC5/irisin mediates the positive effects of physical activity on brain functions. In several brain areas, irisin induces the production of brain-derived neurotrophic factor (BDNF). In the master clock, a significant role in gating photic stimuli in the retinohypothalamic synapse for BDNF is suggested. However, the brain receptor for irisin is unknown yet. In the current review, the interactions of physical activity and the irisin/BDNF axis with the circadian system are reconceptualized.
在哺乳动物中,生理、生化和行为过程在24小时内的时间是由昼夜节律控制的。为了使位于下丘脑视交叉上核的主时钟保持精确的24小时节律,昼夜节律系统使用环境授时因子。这主要是由视网膜通过视网膜下丘脑束发出的信号完成的,但其他信号,如运动、进食、温度、焦虑和社交活动也被证明是非光性授时因子。最近发现的肌因子鸢尾素被认为是运动的一种非光信号。鸢尾素是其前体膜纤维连接蛋白Ⅲ结构域蛋白5 (FNDC5)在运动时裂解和修饰的产物。除了众所周知的外周效应,如白色脂肪细胞的“褐变”,鸢尾素还能穿透血脑屏障,对大脑产生影响。实验数据表明,FNDC5/鸢尾素介导体育活动对脑功能的积极影响。在一些脑区域,鸢尾素诱导脑源性神经营养因子(BDNF)的产生。在主时钟中,BDNF在视网膜下丘脑突触的门控光刺激中起着重要作用。然而,鸢尾素的大脑受体尚不清楚。在当前的综述中,体力活动和鸢尾素/BDNF轴与昼夜节律系统的相互作用被重新定义。
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引用次数: 0
Effects of sevoflurane on left ventricular function by speckle-tracking echocardiography in coronary bypass patients: A randomized trial 七氟醚对冠状动脉搭桥患者左心室功能的影响:一项随机试验
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230173
None Chanjuan Gong, None Xiaokai Zhou, None Yin Fang, None Yanjuan Zhang, None Linjia Zhu, None Zhengnian Ding
The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting (CABG) using transesophageal speckle-tracking echocardiography, and to assess the impact of sevoflurane on cardiac function. Sixty-four patients scheduled for the off-pump CABG were randomly divided into a sevoflurane-based anesthesia (AS) group and a propofol-based total intravenous anesthesia (AA) group. The AS group demonstrated a higher absolute value of left ventricular (LV) global longitudinal strain (GLS) than the AA group at both T1 (after harvesting all grafts and before coronary anastomosis) and T2 (30 min after completing all coronary anastomoses) (P < 0.05). Moreover, strain improvement in the segment with the highest preoperative strain was significantly reduced in the AS group, compared with the AA group at both T1 and T2 (P < 0.01). The flow of the left internal mammary artery-left anterior descending artery graft was superior, and the postoperative concentration of troponin T (cTnT) decreased rapidly in the AS group compared with the AA group (P < 0.05). Compared with total intravenous anesthesia, sevoflurane resulted in significantly higher GLS, stroke volume, and cardiac output. Sevoflurane also led to an amelioration in the condition of the arterial graft. Furthermore, sevoflurane significantly reduced strain improvement in the segmental myocardium with a high preoperative strain value. The findings need to be replicated in large studies.
本研究旨在利用经食管斑点跟踪超声心动图动态观察冠状动脉搭桥术(CABG)中左心室的节段性和全局心肌运动,并评估七氟醚对心功能的影响。64例非体外循环冠脉搭桥患者随机分为七氟醚麻醉(AS)组和异丙酚全静脉麻醉(AA)组。AS组在T1(全部冠脉吻合完成后及吻合前)和T2(全部冠脉吻合完成后30 min)左心室总纵应变(GLS)绝对值均高于AA组(P < 0.05)。在T1和T2时,AS组术前应变最高段的应变改善较AA组均显著降低(P < 0.01)。与AA组相比,AS组左乳内动脉-左前降支血流优势明显,术后肌钙蛋白T (cTnT)浓度迅速下降(P < 0.05)。与全静脉麻醉相比,七氟醚可显著提高GLS、卒中量和心输出量。七氟醚也能改善动脉移植物的状况。此外,七氟醚显著降低节段性心肌的应变改善,术前应变值较高。这些发现需要在大型研究中得到证实。
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引用次数: 0
Phosphorylated protein chip combined with artificial intelligence tools for precise drug screening 磷酸化蛋白芯片结合人工智能工具进行精准药物筛选
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230082
None Katsuhisa Horimoto, None Yuki Suyama, None Tadamasa Sasaki, None Kazuhiko Fukui, None Lili Feng, None Meiling Sun, None Yamin Tang, None Yixuan Zhang, None Dongyin Chen, None Feng Han
We have developed a protein array system, named “Phospho-Totum”, which reproduces the phosphorylation state of a sample on the array. The protein array contains 1 471 proteins from 173 known signaling pathways. According to the activation degrees of tyrosine kinases in the sample, the corresponding groups of substrate proteins on the array are phosphorylated under the same conditions. In addition to the measured phosphorylation levels of the 1 471 substrates, we developed and performed the AI-assisted tools to further characterize the phosphorylation state and estimate pathway activation, tyrosine kinase activation, and a list of kinase inhibitors that produce phosphorylation states similar to that of the sample. The Phospho-Totum system, which seamlessly links and interrogates the measurements and analyses, has the potential to not only elucidate pathophysiological mechanisms in diseases, by reproducing the phosphorylation state of samples, but also be useful for drug discovery, particularly for screening targeted kinases for potential drug kinase inhibitors.
我们开发了一种蛋白质阵列系统,名为“Phospho-Totum”,它可以在阵列上再现样品的磷酸化状态。该蛋白阵列包含来自173个已知信号通路的1471个蛋白。根据样品中酪氨酸激酶的活化程度,在相同条件下对阵列上相应的底物蛋白基团进行磷酸化。除了测量1471个底物的磷酸化水平外,我们开发并执行了人工智能辅助工具,以进一步表征磷酸化状态并估计途径激活、酪氨酸激酶激活以及产生与样品相似的磷酸化状态的激酶抑制剂列表。Phospho-Totum系统无缝连接并询问测量和分析,不仅有可能通过再现样品的磷酸化状态来阐明疾病的病理生理机制,而且对药物发现也很有用,特别是对潜在药物激酶抑制剂的靶向激酶筛选。
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引用次数: 0
Upregulation of α-ENaC induces pancreatic β-cell dysfunction, ER stress, and SIRT2 degradation α-ENaC上调可诱导胰腺β细胞功能障碍、内质网应激和SIRT2降解
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230128
None Xue Zhang, None Dan Zhang, None Lei Huo, None Xin Zhou, None Jia Zhang, None Min Li, None Dongming Su, None Peng Sun, None Fang Chen, None Xiubin Liang
Islet beta cells (β-cells) produce insulin in response to high blood glucose levels, which is essential for preserving glucose homeostasis. Voltage-gated ion channels in β-cells, including Na+, K+, and Ca2+ channels, aid in the release of insulin. Epithelial sodium channel alpha subunit (α-ENaC), a voltage-independent sodium ion channel, is also expressed in human pancreatic endocrine cells. However, there has not been much study done on ENaC's function in β-cells. In the current work, we found that human pancreatic glandule and pancreatic islet β-cells expressed α-ENaC. In the pancreas of db/db mice, high-fat diet-induced obesity, and in mouse islet β-cells (Min6 cells) treated with palmitate, α-ENaC expression was increased. When α-ENaC was overexpressed in Min6 cells, insulin content and glucose-induced insulin secretion were markedly reduced. On the other hand, palmitate injured islet β-cells, suppressed insulin synthesis and secretion, and increased α-ENaC expression in Min6 cells. However, α-ENaC knockout (Scnn1a-/-) in Min6 cells attenuated β-cells disorder induced by palmitate. Furthermore, we revealed that α-ENaC regulated the ubiquitylation and degradation of Sirtuin 2 in β-cells. α-ENaC also modulated β-cell function related to inositol-requiring enzyme 1alpha/X-box-binding protein-1 (IRE1α/XBP1) and protein kinase RNA-like endoplasmic reticulum kinase/C/EBP homologous protein (PERK/CHOP) endoplasmic reticulum stress pathways. These results suggest that α-ENaC plays a novel role in insulin synthesis and secretion in β-cells. Upregulation of α-ENaC promotes islet β-cell dysfunction. As a result, α-ENaC is a key regulator involved in islet β-cell damage and a potential therapeutic target for type 2 diabetes mellitus.
胰岛β细胞(β-细胞)在高血糖水平下产生胰岛素,这对保持葡萄糖稳态至关重要。β细胞中的电压门控离子通道,包括Na+、K+和Ca2+通道,有助于胰岛素的释放。上皮钠离子通道α亚基(α-ENaC)是一种电压无关的钠离子通道,在人胰腺内分泌细胞中也有表达。然而,关于ENaC在β-细胞中的作用的研究还不多。在目前的工作中,我们发现人胰腺和胰岛β-细胞表达α-ENaC。在db/db小鼠的胰腺、高脂饮食诱导的肥胖以及棕榈酸处理的小鼠胰岛β-细胞(Min6细胞)中,α-ENaC表达增加。α-ENaC在Min6细胞中过表达时,胰岛素含量和葡萄糖诱导的胰岛素分泌明显降低。另一方面,棕榈酸酯损伤胰岛β-细胞,抑制胰岛素的合成和分泌,增加Min6细胞α-ENaC的表达。然而,在Min6细胞中敲除α-ENaC (scn1a -/-)可减轻棕榈酸盐诱导的β-细胞紊乱。此外,我们发现α-ENaC调节β-细胞中Sirtuin 2的泛素化和降解。α-ENaC还调节了与肌醇需要酶1α/ x- box结合蛋白1 (IRE1α/XBP1)和蛋白激酶rna样内质网激酶/C/EBP同源蛋白(PERK/CHOP)内质网应激途径相关的β细胞功能。这些结果表明α-ENaC在β-细胞的胰岛素合成和分泌中起着新的作用。α-ENaC上调可促进胰岛β细胞功能障碍。因此,α-ENaC是参与胰岛β细胞损伤的关键调节因子,是2型糖尿病的潜在治疗靶点。
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引用次数: 0
Successful rescue of disseminated <i>Nocardia</i> infection with multiple abscesses in a patient with membranous nephropathy after cardiopulmonary resuscitation: A three-year follow-up 成功抢救弥散性&lt;i&gt;Nocardia&lt;/i&gt;膜性肾病患者心肺复苏后并发多发性脓肿感染:三年随访
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230107
None Yili Xu, None Hanyang Qian, None Wen Qian, None Li Dong, None Weiying Liu, None Yan Zhu, None Yaning Mei, None Yi Xu, None Ling Wang, None Yi Xia, None Xu Qi, None Huanping Mei, None Xueqiang Xu, None Huijuan Mao, None Changying Xing, None Ningning Wang
Nocardiosis manifests as an opportunistic infection, primarily affecting individuals who are immunocompromised and susceptible to the infection. We present a case study of one patient with nephrotic syndrome and membranous nephropathy, who underwent treatment with prednisone and cyclosporine in 2016. In early 2017, the patient was diagnosed with a "fungal infection" and discontinued the use of cyclosporine. After anti-infection therapy for one month, a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region. The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses, multiple lung and brain lesions, and a positive culture of Nocardia in the drainage. We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole (TMP-SMX), minocycline, and voriconazole. However, the patient experienced sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation. During the five-month follow-up period following the discharge, the patient displayed an enhanced nutritional status and stable renal function. The focal infection ultimately resolved during the subsequent three years. Neuro-infection caused by Nocardia should be considered in immunocompromised patients, and TMP-SMX is the preferred initial therapy; however, given the high mortality rate, long-term combination therapy with imipenem, cefotaxime, amikacin and TMP-SMX is suggested.
诺卡菌病表现为机会性感染,主要影响免疫功能低下和易受感染的个体。我们报告了一例肾病综合征和膜性肾病患者的病例研究,该患者于2016年接受了泼尼松和环孢素的治疗。2017年初,该患者被诊断为“真菌感染”,并停止使用环孢素。抗感染治疗一个月后,颅磁共振成像扫描显示右侧颞区多发脓肿。诺卡菌病的诊断是基于转移性脓肿肿块,多发性肺和脑病变,以及引流液中诺卡菌培养阳性。我们将抗感染治疗改为甲氧苄啶-磺胺甲恶唑(TMP-SMX)、米诺环素和伏立康唑的联合治疗。然而,患者经历了心脏骤停,随后在心肺复苏后恢复。出院后随访5个月,患者营养状况改善,肾功能稳定。局灶性感染在随后的三年中最终消退。免疫功能低下患者应考虑诺卡菌引起的神经感染,TMP-SMX是首选的初始治疗方案;然而,鉴于死亡率高,建议长期联合亚胺培南、头孢噻肟、阿米卡星和TMP-SMX治疗。
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引用次数: 0
Anticancer therapeutic strategies for targeting mutant p53-Y220C 靶向p53-Y220C突变体的抗癌治疗策略
Pub Date : 2023-01-01 DOI: 10.7555/jbr.37.20230093
None Vitaly Chasov, None Damir Davletshin, None Elvina Gilyazova, None Regina Mirgayazova, None Anna Kudriaeva, None Raniya Khadiullina, None Youyong Yuan, None Emil Bulatov
The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2 (MDM2, also termed HDM2 in humans) through a feedback mechanism. At the same time TP53 is the most frequently mutated gene in human cancers. Mutant p53 proteins lose wild-type p53 tumor suppression functions and acquire new oncogenic properties among which are deregulated cell proliferation, increased chemoresistance, disruption of tissue architecture, promotion of migration, invasion and metastasis, and several other pro-oncogenic activities. The oncogenic p53 mutation Y220C, which accounts for over 100 000 cancer cases per year, creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation. This cavity can accommodate stabilizing small molecules that have therapeutic value. The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein. In this review we summarize approaches that target p53-Y220C, including reactivating this mutation with small molecules that bind Y220C hydrophobic pocket and developing immunotherapies as the goal of near future, which could target tumor cells that express the p53- Y220C neoantigen.
肿瘤抑制因子p53是一种具有强大抗肿瘤活性的转录因子,其负调节因子MDM2(在人类中也称为HDM2)通过反馈机制控制其抗肿瘤活性。同时,TP53是人类癌症中最常见的突变基因。突变型p53蛋白失去了野生型p53的抑瘤功能,并获得了新的致癌特性,其中包括细胞增殖失调、化疗耐药增加、组织结构破坏、促进迁移、侵袭和转移以及其他几种促癌活性。致癌的p53突变Y220C每年导致超过10万例癌症病例,它在dna结合域产生一个延伸的表面裂缝,使p53不稳定,并导致其变性和聚集。这个空腔可以容纳具有治疗价值的稳定小分子。开发合适的小分子稳定剂是重新激活Y220C突变蛋白的治疗策略之一。在这篇综述中,我们总结了针对p53-Y220C的方法,包括用结合Y220C疏水袋的小分子重新激活该突变,以及开发免疫疗法作为近期的目标,这些疗法可以靶向表达p53-Y220C新抗原的肿瘤细胞。
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引用次数: 0
Evaluation of the adjuvanticity of artemisinin with soluble Leishmania major antigens in BALB/c mice 青蒿素对BALB/c小鼠可溶性利什曼原虫主抗原的佐剂性评价
Pub Date : 2009-11-01 DOI: 10.1016/S1007-4376(09)60084-8
Albert Kimutai , Willy K. Tonui , Michael M. Gicheru , Peter Kamau Ngure , Johnstone Ingonga , Stella Kepha , Laban Ireri Njeru , Dorcas Wachira , Robert Karanja Muhia , Milkah Mwangi , Lydia B. Nyamwamu

Objective

To determine the adjuvant potential of artemisinin with a soluble leishmanial antigen in vaccinating BALB/c mice.

Methods

Seventy two female BALB/c mice were randomly assigned into six groups. The mice were vaccinated with soluble leishmania antigens (SLA) alone, artemisinin co-administered with SLA, SLA and Bacille Calmette Guérin (BCG) vaccine, and artemisinin and BCG alone. Unvaccinated mice formed the control group. The induction of cell-mediated immunity following vaccination was determined by measuring in vitro lymphocyte proliferation and the production of interleukin (IL)-4, IL-5 and gamma interferon (IFN-γ) determined by flow cytometry. Protection against L. major was determined by quantifying parasite burdens in L. major infected footpads using a limiting dilution assay and by measuring lesion sizes of the infected footpad compared to the contralateral uninfected footpad.

Results

Mice receiving SLA plus artemisinin produced significantly high levels of IL-4 and IL-5 (P < 0.05) and low levels of IFN-γ, resulting in exacerbated disease. In addition, subcutaneous administration of SLA + artemisinin, artemisinin alone or SLA alone resulted in the development of large footpad swellings and high parasite loads that were comparable to those of the control unvaccinated mice (P > 0.05), resulting in exacerbated disease.

Conclusion

These data suggest that artemisinin is not a suitable adjuvant for Leishmania vaccines. However, since artemisinin has been shown to be effective against Leishmania parasites in vitro and in vivo, further studies ought to be conducted to determine its immunochemotherapeutic potential when co-administered with Leishmania antigens.

目的研究青蒿素与可溶性利什曼抗原对BALB/c小鼠的佐剂作用。方法将72只雌性BALB/c小鼠随机分为6组。小鼠分别接种可溶性利什曼原虫抗原(SLA)、青蒿素与可溶性利什曼原虫抗原(SLA)、可溶性利什曼原虫抗原(SLA)和卡介苗(BCG)联合接种、青蒿素和卡介苗单独接种。未接种疫苗的小鼠作为对照组。通过测定体外淋巴细胞增殖和流式细胞术测定白细胞介素(IL)-4、IL-5和γ干扰素(IFN-γ)的产生,确定疫苗接种后细胞介导免疫的诱导。采用极限稀释法定量测定大螺杆菌感染足垫的寄生虫负荷,并测量感染足垫与对侧未感染足垫的病变大小,从而确定对大螺杆菌的保护作用。结果SLA +青蒿素组小鼠IL-4、IL-5水平显著升高(P <0.05)和低水平的IFN-γ,导致疾病加重。此外,皮下注射SLA +青蒿素、单独使用青蒿素或单独使用SLA可导致足垫肿胀和高寄生虫载量,与未接种疫苗的对照组小鼠相当(P >0.05),导致病情加重。结论青蒿素不适合作为利什曼原虫疫苗的佐剂。然而,由于青蒿素已被证明在体外和体内对利什曼原虫寄生虫有效,因此应进行进一步的研究,以确定其与利什曼原虫抗原共同施用时的免疫化疗潜力。
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引用次数: 3
Maxillary first premolars: I. Morphology of the apical constriction 上颌第一前磨牙:1 .牙尖缩窄的形态学
Pub Date : 2009-11-01 DOI: 10.1016/S1007-4376(09)60093-9
Daming Wu, Younong Wu, Ming Hu

Objective

To investigated the apical constriction morphology of maxillary first premolars in the Chinese population.

Methods

Eighty recently extracted human maxillary first premolars from a native Chinese population were used. The number and shape of apical constrictions were recorded under a dental operating microscope (DOM) at 12.5 × 2.5 magnification. After access preparation, a new K-file was inserted into the canal until the tip of the file was just seen at the apical constriction under the DOM. The teeth with files in the canals were X-rayed from a mesiodistal direction using a direct digital radiography (DDR) system, and the distance between the file tip and the center of radiographic apex was directly measured from the computer screen using DDR measurement software.

Results

The percentage of teeth with an apical constriction was 78.5% (102/130). The most common apical constriction shapes were oval (55.9%) and round (35.3%). The mean distance between the apical constriction and the anatomical tip of the root was 0.61 mm, and 84.3% (86/102) were within 1 mm.

Conclusion

The most common shape of an apical constriction was oval or round, and the distance to the apex was mostly within 1 mm, indicating that root canal therapy should stop 1 mm from the radiographic apex.

目的探讨中国人上颌第一前磨牙的尖缩形态。方法使用80颗最近从中国土著人群中提取的上颌第一前磨牙。在12.5 × 2.5倍的牙科手术显微镜下记录根尖缩窄的数量和形状。通路准备后,将新的k锉插入管中,直到锉的尖端正好在DOM下的根尖缩窄处。采用直接数字x线摄影(DDR)系统对根管内有锉的牙齿进行中远端x线拍摄,用DDR测量软件在计算机屏幕上直接测量锉尖与根尖中心之间的距离。结果牙根尖缩窄率为78.5%(102/130)。最常见的根尖狭窄形状为椭圆形(55.9%)和圆形(35.3%)。根尖缩窄与根尖解剖尖的平均距离为0.61 mm,其中84.3%(86/102)在1 mm以内。结论根尖缩窄最常见的形状为椭圆形或圆形,到根尖的距离多在1 mm以内,提示根管治疗应在距离根尖1 mm处停止。
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引用次数: 0
Efficacy of gefitinib as a first-line single agent treatment in patients with advanced non-small cell lung cancer 吉非替尼作为一线单药治疗晚期非小细胞肺癌的疗效
Pub Date : 2009-11-01 DOI: 10.1016/S1007-4376(09)60088-5
Yongmei Yin , Yiting Geng , Xiaodong Li, Xiaoli Hu, Xiaofeng Chen, Wei Li, Yongqian Shu

Objective

To assess the efficacy and toxicity of gefitinib as a single agent treatment in Chinese patients with advanced non-small cell lung cancer (NSCLC).

Methods

Forty-five patients with advanced NSCLC were treated with gefitinib at 250 mg daily until the disease progressed or the patient could not tolerate the toxicity.

Results

None of the patients achieved a complete response (CR), while 15 patients achieved a partial remission (PR) and 17 experienced a stable disease (SD). Thirteen patients continued to have a progressive disease (PD). The response rate and the disease control rate were 33.3% and 71.1%, respectively. The symptom remission rate was 72.5%, and the median remission time was 8 days. The median survival time was 15.3 months. The median progression-free survival time was 6.0 months. The most common toxicities included rash (53.3%) and diarrhea (33.3%). Dehydration and pruritus of the skin developed in 26.7% and 22.2% of the patients, respectively. Hepatic toxicity occurred in 6.7% of patients and oral ulceration occurred in 4.4% of patients.

Conclusion

Single agent treatment with gefitinib is effective against advanced NSCLC, and is well tolerated in Chinese patients.

目的评价吉非替尼单药治疗中国晚期非小细胞肺癌(NSCLC)的疗效和毒性。方法45例晚期非小细胞肺癌患者采用每日250mg吉非替尼治疗,直至病情进展或患者不能耐受其毒性。结果1例患者完全缓解(CR), 15例部分缓解(PR), 17例病情稳定(SD)。13例患者病情持续进展(PD)。有效率为33.3%,疾病控制率为71.1%。症状缓解率为72.5%,中位缓解时间为8天。中位生存时间为15.3个月。中位无进展生存期为6.0个月。最常见的毒性包括皮疹(53.3%)和腹泻(33.3%)。26.7%和22.2%的患者出现皮肤脱水和瘙痒。6.7%的患者发生肝毒性,4.4%的患者发生口腔溃疡。结论吉非替尼单药治疗晚期NSCLC疗效显著,且耐受性良好。
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引用次数: 3
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Journal of Nanjing Medical University
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