SYNTAX Ⅱ积分对急性ST段抬高型心肌梗死患者预后的预测价值

 目的 探讨SYNTAX Ⅱ积分对急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者预后的预测价值。方法 采用回顾性分析方法,收集解放军总医院第三医学中心2014-01至2016-06确诊为急性STEMI,且行直接经皮冠状动脉介入治疗(primary percutaneous coronary intervention,PPCI)的患者445例。每例患者用SYNTAX Ⅱ积分系统评分,并记录发生主要不良心血管事件(major adverse cardiac events,MACE)的情况。根据评分将患者分为SYNTAX Ⅱ低分组和高分组。比较各临床因素对两组患者的影响;比较两组间终点事件的发生率和死亡率;分析急性STEMI患者全因死亡的影响因素和独立影响因素。结果 两组患者在年龄、性别、吸烟史、射血分数和Killip分级的比较中差异有统计学意义(P<0.05)。两组间终点事件发生率和死亡率比较,差异有统计学意义(P<0.05)。单因素分析显示:年龄、吸烟史、射血分数、血肌酐值、Killip 分级Ⅱ—Ⅳ级和SYNTAX Ⅱ积分是急性STEMI患者全因死亡的影响因素。COX回归分析表明:年龄(OR=1.696,95% CI 1.037～2.359)、射血分数(OR=0.810,95% CI 0.713～0.907)和SYNTAX Ⅱ积分(OR=1.309,95% CI 1.132～1.317)是急性STEMI患者全因死亡的独立危险因素。结论 SYNTAX Ⅱ积分是急性STEMI患者全因死亡的独立危险因素。随着SYNTAX Ⅱ积分的增加,MACE发生率增高,发生时间越早,其全因死亡率和心源性死亡率越高。     

足月新生儿肝母细胞瘤CT影像特征分析

目的探讨足月新生儿肝母细胞瘤(HB)的CT特征。方法回顾性分析2015年1月至2019年1月在湖南省儿童医院经手术病理证实的7例新生儿肝母细胞瘤的临床资料及腹部CT表现特点,重点观察肿块的位置、大小、形态、密度及动态增强特征。结果7例HB患儿CT表现为肝内单发性肿块,其中累及肝Ⅵ段2例、肝Ⅶ段2例、肝Ⅴ+Ⅵ段1例、肝Ⅱ+Ⅲ段1例、肝Ⅳa+Ⅴ+Ⅷ段1例。肿瘤最大径为2.9~10.2 cm,中位数为4.7 cm;类球形4例,不规则分叶状且突向肝外生长3例;边界清晰6例,边界模糊1例;瘤内坏死囊变4例,钙化1例,小片状出血5例;7例肿瘤均呈不均匀强化,动脉期肿瘤中心及边缘出现多发结节状、条片状明显强化;门静脉期及延迟期强化呈进行性区域扩展、充填,呈多发条索状及"岛屿样"强化,且以边缘强化明显,坏死囊变区无强化;1例肿瘤侵犯门静脉及肝门区胆管,并肝内胆管扩张;3例腹腔干水平以下腹主动脉管径变细。病理诊断示肝母细胞瘤上皮胎儿型6例,混合型1例。结论新生儿HB的主要CT表现为可伴有不同程度坏死、出血及钙化的类球形或分叶状肿块,增强扫描呈进行性区域扩展的不均匀明显强化。     

The effect of enhancing quality of life in patients intervention for advanced lung cancer: Protocol for a randomized clinical study

Objective:The objective of this present research is to evaluate the effect of the intervention of enhancing quality of life in patients in patients with advanced lung cancer.Methods:Our research is carried out as a randomized clinical trial which will be implemented from December 2020 to October 2021. It was approved by the Ethics Committee of People''s Hospital of Chengyang District (03982790). This study includes 90 patients with advanced lung cancer. Patients diagnosed at our oncology clinic are eligible if they are diagnosed within 8 weeks of a novel diagnosis of stage 3 or stage 4 lung cancer. Patients with hepatic insufficiency, renal failure, and respiratory and heart failure, as well as a series of severe mental illness are excluded from our research. Patients are divided randomly into the intervention group and control group, each group is assigned 45 patients. Through utilizing functional assessment of cancer therapy–lung, the measurement of life quality is conducted. And the measurement of mood is carried out with Hospital Anxiety and Depression Scale.Results:Table 1 indicates the patient''s life quality and Hospital Anxiety and Depression Scale in both groups.Conclusion:Enhancing quality of life in patient intervention may be beneficial to improve the life quality in advanced lung cancer patients.Trial registration: The protocol was registered in Research Registry (researchregistry6243)     

Budd- Chiari综合征患者介入开通术后再狭窄处理和远期随访结果

【摘要】 目的 探讨Budd-Chiari综合征患者介入开通术后再狭窄的治疗策略,评价远期随访结果。 方法 回顾性分析1983年11月至2013年12月60例原发性Budd-Chiari综合征介入开通术后出现再狭窄患者临床资料和随访结果。 结果 60例再狭窄患者根据初始开通术式分为单纯PTA治疗组（40例,其中混合型27例,下腔静脉型5例,肝静脉型8例）、PTA+支架植入组（20例,其中混合型13例,下腔静脉型6例,肝静脉型1例）。单纯PTA治疗组出院1年内、5年内、10年内发生再狭窄分别为15例（37.5%）、34例（85%）、38例（95%）,PTA+支架植入组出院1年内、5年内、10年内发生再狭窄分别为10例（50%）、18例（90%）、19例（95%）。单纯PTA治疗组中13例拒绝治疗, 27例接受进一步治疗,其中5例随访中出现第2次再狭窄,2例第3次再狭窄,1例第4次再狭窄;PTA+支架植入组中9例拒绝治疗,10例仅接受单纯PTA,另1例接受PTA+支架植入,5例随访中发生第2次再狭窄,3例第3次再狭窄,1例第4次再狭窄。38例再狭窄后接受进一步治疗患者1年、5年、10年、20年、25年累积生存率分别为分别为100%、78.3%、78.3%、70.5%、70.5%,22例拒绝进一步治疗患者分别为72.7%、45.9%、30.6%、10.2%、NA（未获得）,两部分患者间差异有显著统计学意义（P＜0.001）。 结论 Budd-Chiari综合征患者介入开通术后远期随访非常重要。积极治疗再狭窄可改善患者预后。根据疗效逐步升级侵入性治疗策略,取得了满意的结果。     

Altered brain functional connectivity in hemodialysis patients with end-stage renal disease: a resting-state functionalMR imaging study

The changes of whole brain functional connectivity in hemodialysis (HD) patients with end-stage renal disease (ESRD) are still unclear, which may be associated with multiple factors, such as elevated neurotoxins, anemia, and side effects of hemodialysis. Resting-state functional magnetic resonance imaging (rs-fMRI) data of 71 patients (43 males, 28 females; mean age, 33.4?±?9.4 years) and 43 age- and gender-matched healthy volunteers (29 males, 14 females; mean age, 30.6?±?8.8 years) were acquired. Neuropsychological tests including number connection test type A (NCT-A), digit symbol test (DST), line-tracing test (LTT), serial-dotting test (SDT), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to evaluate cognitive and psychiatric conditions in all subjects. Blood biochemistry tests including serum creatinine levels, blood urea, hematocrit, and Ca²⁺ level were taken in HD patients. Forty-two connections significantly different between HD patients with ESRD and controls were found (all P?ESRD patients was more directly related with neuropsychological impairments and anemia rather than serum creatinine level, blood urea and dialysis duration. In particular, impairments in the medial prefrontal lobe could play an important role in mediating psychological dysfunctions.     

胰岛素样生长因子-1对氯化钴诱导的PC12细胞凋亡的抑制作用

目的 探讨胰岛素样生长因子-1（IGF-1）对氯化钴（CoCl2）诱导的肾上腺嗜铬细胞瘤 PC12细胞凋亡的作 用及机制。方法 取对数生长期的 PC12细胞,分别以 10、20、40、80 μmol/L的 CoCl2溶液和 100、200、400 μg/L的 IGF- 1溶液处理细胞,CCK-8法检测细胞活力,得出 CoCl2和 IGF-1最佳干预浓度。根据选定的实验条件,应用 CoCl2处理 PC12细胞建立 HIE细胞模型,实验分为对照组、CoCl2处理组、IGF-1+CoCl2处理组。分组处理 24 h后采用 CCK-8法 检测细胞存活率;TUNEL染色检测细胞凋亡情况;Western blot检测各组细胞 Bax、Bcl-2及 Caspase-3的蛋白的表达 水平。最后在上述实验的基础上,设 CoCl2处理组、CoCl2+IGF-1处理组、HIF-1α抑制剂 2-甲氧雌二醇（2-MeOE2）+ CoCl 2组和 CoCl2+2-MeOE2+IGF-1组,Western blot观察 IGF-1、2-MeOE2及两者共用对 PC12细胞 HIF-1α及 Bax的表 达水平的影响。结果 CCK-8检测结果显示,40 μmol/L CoCl2和 200 μg/L IGF-1为最佳干预浓度。利用以上浓度分 组干预细胞 24 h后,与 CoCl2组相比,IGF-1+CoCl2处理组细胞存活率明显提升,TUNEL阳性细胞数和细胞比例降低, 同时抗凋亡蛋白 Bcl-2表达上调,促凋亡蛋白 Bax、Caspase-3,HIF-1α表达下调,差异均有统计学意义（均P＜0.05）。 应用 2-MeOE2对细胞进行预处理后,CoCl2+2-MeOE2组与 2-MeOE2+IFG-1组 HIF-1α和 Bax蛋白表达差异无统计 学意义,但均较 CoCl2+IGF-1组明显下调（P＜0.01）。结论 IGF-1可抑制 CoCl2诱导的 PC12细胞凋亡,其保护作用 可能与 HIF-1α表达下调有关。     

基于牙体牙髓、牙周及功能健康的 显微微创牙体预备

牙体预备技术是口腔美学修复治疗必知必会的核心操作,通过一定量的牙修复体组织的磨除,为目标修复体提供容纳空间、粘接面与完成线等。如何在完成高质量牙体预备的同时还能保存牙体、保护活髓和牙周组织是美学修复牙体预备中亟需解决的难题。本文就微创牙体预备的概念及核心要素,显微牙体预备涉及的解剖生理学、显微牙体预备术前设计进行介绍,并总结了显微牙体预备技术临床路径,提出了显微牙体预备核心因素——量与形的新认知。     

Taxodione and arenarone inhibit farnesyl diphosphate synthase by binding to the isopentenyl diphosphate site

We used in silico methods to screen a library of 1,013 compounds for possible binding to the allosteric site in farnesyl diphosphate synthase (FPPS). Two of the 50 predicted hits had activity against either human FPPS (HsFPPS) or Trypanosoma brucei FPPS (TbFPPS), the most active being the quinone methide celastrol (IC₅₀ versus TbFPPS ∼20 µM). Two rounds of similarity searching and activity testing then resulted in three leads that were active against HsFPPS with IC₅₀ values in the range of ∼1–3 µM (as compared with ∼0.5 µM for the bisphosphonate inhibitor, zoledronate). The three leads were the quinone methides taxodone and taxodione and the quinone arenarone, compounds with known antibacterial and/or antitumor activity. We then obtained X-ray crystal structures of HsFPPS with taxodione+zoledronate, arenarone+zoledronate, and taxodione alone. In the zoledronate-containing structures, taxodione and arenarone bound solely to the homoallylic (isopentenyl diphosphate, IPP) site, not to the allosteric site, whereas zoledronate bound via Mg²⁺ to the same site as seen in other bisphosphonate-containing structures. In the taxodione-alone structure, one taxodione bound to the same site as seen in the taxodione+zoledronate structure, but the second located to a more surface-exposed site. In differential scanning calorimetry experiments, taxodione and arenarone broadened the native-to-unfolded thermal transition (T_m), quite different to the large increases in ΔT_m seen with biphosphonate inhibitors. The results identify new classes of FPPS inhibitors, diterpenoids and sesquiterpenoids, that bind to the IPP site and may be of interest as anticancer and antiinfective drug leads.Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate (IPP; compound 1 in Fig. 1) with dimethylallyl diphosphate (DMAPP; compound 2 in Fig. 1) to form the C₁₀ isoprenoid geranyl diphosphate (GPP; compound 3 in Fig. 1), which then condenses with a second IPP to form the C₁₅ isoprenoid, farnesyl diphosphate (FPP; compound 4 in Fig. 1). FPP then is used in a wide range of reactions including the formation of geranylgeranyl diphosphate (GGPP) (1), squalene (involved in cholesterol and ergosterol biosynthesis), dehydrosqualene (used in formation of the Staphylococcus aureus virulence factor staphyloxanthin) (2), undecaprenyl diphosphate (used in bacterial cell wall biosynthesis), and quinone and in heme a/o biosynthesis. FPP and GGPP also are used in protein (e.g., Ras, Rho, Rac) prenylation, and FPPS is an important target for the bisphosphonate class of drugs (used to treat bone resorption diseases) such as zoledronate (compound 5 in Fig. 1) (3). Bisphosphonates targeting FPPS have activity as antiparasitics (4), act as immunomodulators (activating γδ T cells containing the Vγ2Vδ2 T-cell receptor) (5), and switch macrophages from an M2 (tumor-promoting) to an M1 (tumor-killing) phenotype (6). They also kill tumor cells (7) and inhibit angiogenesis (8). However, the bisphosphonates in clinical use (zoledronate, alendronate, risedronate, ibandronate, etidronate, and clodronate) are very hydrophilic and bind avidly to bone mineral (9). Therefore, there is interest in developing less hydrophilic species (10) that might have better activity against tumors in soft tissues and better antibacterial (11) and antiparasitic activity.Open in a separate windowFig. 1.Chemical structures of FPPS substrates, products, and inhibitors.The structure of FPPS (from chickens) was first reported by Tarshis et al. (12) and revealed a highly α-helical fold. The structures of bacterial and Homo sapiens FPPS (HsFPPS) are very similar; HsFPPS structure (13, 14) is shown in Fig. 2A. There are two substrate-binding sites, called here “S1” and “S2.” S1 is the allylic (DMAPP, GPP) binding site to which bisphosphonates such as zoledronate bind via a [Mg²⁺]₃ cluster (15) (Fig. 2B). S2 is the homoallylic site to which IPP binds, Fig. 2B. Recently, Jahnke et al. (10) and Salcius et al. (16) discovered a third ligand-binding site called the “allosteric site” (hereafter the “A site”). A representative zoledronate+A-site inhibitor structure [Protein Data Bank (PDB) ID code 3N46] (Nov_980; compound 6 in Fig. 1) showing zoledronate in S1 and Nov_980 (compound 6) in the A site is shown in a stereo close-up view in Fig. 2B, superimposed on a zoledronate+IPP structure (PDB ID code 2F8Z) in S2. Whether the allosteric site serves a biological function (e.g., in feedback regulation) has not been reported. Nevertheless, highly potent inhibitors (IC₅₀ ∼80 nM) have been developed (10), and the best of these newly developed inhibitors are far more hydrophobic than are typical bisphosphonates (∼2.4–3.3 for cLogP vs. ∼−3.3 for zoledronate) and are expected to have better direct antitumor effects in soft tissues (10).Open in a separate windowFig. 2.Structures of human FPPS. (A) Structure of HsFPPS showing zoledronate (compound 5) and IPP (compound 1) bound to the S1 (allylic) and S2 (homoallylic) ligand-binding sites (PDB ID code 2F8Z). (B) Superposition of the IPP-zoledronate structure (PDB ID code 2F8Z) on the zoledronate-Nov_980 A-site inhibitor structure (PDB ID code 3N46). Zoledronate binds to the allylic site S1, IPP binds to the homoallylic site S2, and the allosteric site inhibitor binds to the A site. Active-site “DDXXD” residues are indicated, as are Mg²⁺ molecules (green and yellow spheres, respectively). The views are in stereo.In our group we also have developed more lipophilic compounds (e.g., compound 7 in Fig. 1) (17, 18) as antiparasitic (19) and anticancer drug leads (18) and, using computational methods, have discovered other novel nonbisphosphonate FPPS inhibitors (e.g., compound 8 in Fig. 1) that have micromolar activity against FPPS (20). In this study, we extended our computational work and tried to discover other FPPS inhibitors that target the A site. Such compounds would be of interest because they might potentiate the effects of zoledronate and other bisphosphonates, as reported for other FPPS inhibitors (21), and have better tissue distribution properties in general.