关节镜下经髌腱入路空心拉力螺钉复位固定治疗胫骨髁间嵴撕脱骨折*

目的探讨在关节镜下经髌腱入路,利用空心拉力螺钉复位固定胫骨髁间嵴撕脱骨折(TEFx)的安全性和有效性。方法选取2014年1月-2015年12月23例TEFx的患者,均在关节镜下经髌腱入路,用空心拉力螺钉复位固定。术前Meyers-McKeever分型:Ⅱ型8例,Ⅲ型10例,Ⅳ型5例;男17例,女6例;年龄16～53岁,平均27.8岁。术前前抽屉试验、Lachman试验均阳性。比较术前术后的视觉模拟评分(VAS)、Lysholm、Tegner和国际膝关节文献委员会(IKDC)评分评价患侧膝关节功能。结果 23例患者均得到随访,随访时间30～40个月,平均36个月。术后即刻X线片示TEFx均复位良好,术后3个月骨折均愈合。无1例感染、关节僵硬、伸直受限、复位丢失及神经血管损伤等并发症。最终随访患侧膝关节活动度均恢复正常,前抽屉试验、Lachman试验均阴性。VAS评分术前(4.8±1.2)分,最终随访为(1.2±0.8)分,术前术后比较,差异有统计学意义(t=18.72,P=0.003);Lysholm评分术前为(50.8±6.2)分,最终随访为(90.8±5.4)分,术前术后比较,差异有统计学意义(t=-42.64,P=0.000);Tegner评分术前为(4.0±1.0)分,最终随访为(5.1±1.2)分,术前术后比较,差异有统计学意义(t=-16.82,P=0.005);IKDC主观评分术前为(52.5±7.4)分,最终随访为(91.5±5.7)分,术前术后比较,差异有统计学意义(t=-40.58,P=0.000)。结论膝关节镜下经髌腱入路空心拉力螺钉内固定治疗TEFx具有微创、操作简捷、固定可靠和恢复快的优点。     

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR.MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC_0–∞, AUC_0–t, and C_max) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The C_max and AUC_0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments.FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin C_max was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported.ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.     

新生儿重症监护室护士经历道德困扰体验的现象学研究

目的了解新生儿重症监护室护士经历道德困扰的心理体验及应对方式。方法采用现象学研究方法,对14名新生儿重症监护室护士进行一对一的半结构式访谈,访谈内容根据Colaizzi的资料分析方法进行整理、提炼主题。结果新生儿重症监护室护士经历道德困扰的心理体验包括:失落与气愤、伤心与难过、无力与受挫、麻木与淡漠;应对方式包括:被动接受、心理弹性、寻求措施。结论由于照护对象的特殊性,新生儿重症监护室护士产生道德困扰的情境较为复杂,易给护士带来消极情绪,但却很少受到管理者重视。今后应进一步探究减轻护士道德困扰的干预方法,以合理利用人力资源,提高护理质量。     

Two sphingomyelin synthase homologues regulate body weight and sphingomyelin synthesis in female brown planthopper,N. lugens (Stål)

Although sphingomyelins known to be are lipid constituents of the plasma membrane in vertebrates, much remains obscure about the metabolism of sphingomyelins in insects. With ultra performance liquid chromatography‐time‐of‐flight‐tandem mass spectrometry analysis, we revealed for the first time that sphingomyelins are abundant in Nilaparvata lugens (Stål), the brown planthopper (BPH), and their biosynthesis is carried out by sphingomyelin synthase‐like protein 2 (SMSL2), which is homologous to sphingomyelin synthase‐related protein (SMSr). Unlike other insect species, high concentrations of sphingomyelins rather than ceramide phosphoethanolamines exist in the BPH. Two putative genes, which are homologous to SMSr, are named Nilaparvata lugens SMS‐like 1 (NlSMSL1) and 2 (NlSMSL2). Knockdowns of both NlSMSL2 and NlSMSL1 were conducted but only the first decreased concentrations of sphingomyelins in the BPH, indicating that NlSMSL2 plays a role in the biosynthesis of sphingomyelins. Real‐time quantitative PCR analysis revealed both NlSMSL1 and NlSMSL2 are highly expressed in BPH adults, with NlSMSL1 specifically highly expressed in reproductive organs (ovaries and testes) whereas NlSMSL2 was highly expressed in the malpighian tubules. The knockdown of NlSMSL1 or NlSMSL2 increased BPH female body weight but not that of males, suggesting sex‐specific roles for SMSLs in influencing BPH body weight. The results suggest that NlSMSL2 catalyses the synthesis of sphingomyelins and maintains female BPH body weight through alteration of sphingolipid content.     

Tumor-associated Macrophage-derived Interleukin-23 Interlinks Kidney Cancer Glutamine Addiction with Immune Evasion

Background

Glutamine addiction is a hallmark of clear cell renal cell carcinoma (ccRCC); yet whether glutamine metabolism impacts local immune surveillance is unclear. This knowledge may yield novel immunotherapeutic opportunities.

Application of neuroendoscopic surgical techniques in the assessment and treatment of cerebral ventricular infection

Cerebral ventricular infection(CVI) is one of the most dangerous complications in neurosurgery because of its high mortality and disability rates. Few studies have examined the application of neuroendoscopic surgical techniques(NESTs) to assess and treat CVI. This multicenter, retrospective study was conducted using clinical data of 32 patients with CVI who were assessed and treated by NESTs in China. The patients included 20 men and 12 women with a mean age of 42.97 years. NESTs were used to obliterate intraventricular debris and pus, fenestrate or incise the intraventricular compartment and reconstruct cerebrospinal fluid circulation, and remove artificial material. Intraventricular irrigation with antibiotic saline was applied after neuroendoscopic surgery(NES). Secondary hydrocephalus was treated by endoscopic third ventriculostomy or a ventriculoperitoneal shunt. Neuroendoscopic findings of CVI were used to classify patients into Grade I(n = 3), Grade II(n = 13), Grade III(n = 10), and Grade IV(n = 6) CVI. The three patients with grade I CVI underwent one NES,the 23 patients with grade II/III CVI underwent two NESs, and patients with grade IV CVI underwent two(n = 3) or three(n = 3) NESs.The imaging features and grades of neuroendoscopy results were positively related to the number of neurosurgical endoscopic procedures.Two patients died of multiple organ failure and the other 30 patients fully recovered. Among the 26 patients with secondary hydrocephalus,18 received ventriculoperitoneal shunt and 8 underwent endoscopic third ventriculostomy. There were no recurrences of CVI during the 6-to 76-month follow-up after NES. Application of NESTs is an innovative method to assess and treat CVI, and its neuroendoscopic classification provides an objective, comprehensive assessment of CVI. The study trial was approved by the Institutional Review Board of Beijing Shijitan Hospital, Capital Medical University, China.     

糖尿病合并白内障及单纯老年性白内障与房水中细胞因子相关性的临床研究

目的探讨糖尿病合并白内障及单纯老年性白内障与房水中细胞因子的相关性。 方法收集2017年10月至2018年2月在内蒙古医科大学附属医院接受白内障手术治疗49例患者(49只眼)的临床资料。其中，男性22例(22只眼)，女性27例(27只眼)，平均年龄(64.4±9.7)岁。依据患者是否患有糖尿病，分为实验1组和实验2组。其中，糖尿病合并白内障患者14例(14只眼)为实验1组；单纯老年性白内障患者35例(35只眼)为实验2组。所有患者白内障术中收集房水。采用细胞因子微球技术检测患者血清及房水中白细胞介素-8(IL-8)、白细胞介素-10(IL-10)、血管内皮生长因子(VEGF)、血管细胞粘附分子-1(VCAM-1)及成纤维细胞生长因子(bFGF)的浓度，酶联免疫吸附试验检测人血管内皮细胞生长因子B(VEGF-B)和胎盘生长因子(PLGF)的浓度。采用Spearman相关分析评价两组房水中各细胞因子浓度与晶状体皮质混浊、核性混浊及后囊下混浊的相关性。 结果实验1组和2组患者房水中IL-8、IL-10、VEGF、BFGF、VCAM-1、PLGF、VEGF-B浓度分别为(31.69±27)pg/ml、(5.2±0.41)pg/ml、(47.27±20.58)pg/ml、(17.28±4.11)pg/ml、(416.5±310.66)pg/ml、(17.85±6.70)pg/ml、(65.54±26.89)pg/ml、(12.38±6.52)pg/ml、(3.7±2.13)pg/ml、(36.54±14.97)pg/ml、(17.43±4.33)pg/ml、(331.39±205.80)pg/ml、(22.21±17.47)pg/ml及(74.36±26.75)pg/ml。实验1组房水中VCAM-1浓度与晶状体核性混浊呈负相关(r＝-0.61，P<0.05)。实验1组和2组患者血清中各细胞因子与晶状体核性混浊无相关性(r＝-0.03，-0.10，0.26，0.04，-0.32，-0.19；P均>0.05)、(r＝-0.15，0.13，-0.15，-0.11，0.11，-0.18；P均>0.05)、(r＝0.21，0.53，0.20，0.13，-0.12，0.16；P均>0.05)、(r＝-0.06，0.03，-0.01，-0.20，0.09，0.20；P均>0.05)、(r＝0.39，0.02，-0.11，-0.20，-0.13，0.03；P均>0.05)及(r＝0.13，0.09，0.32，0.25，0.11，-0.10；P均>0.05)。 结论两组房水中细胞因子与白内障之间规律不同。糖尿病患者房水中VCAM-1的浓度与晶状体的核性混浊呈负相关，VCAM-1可能是核性白内障的保护性因素。