Acute Acquired Concomitant Esotropia: Clinical features,Classification, and Etiology

Acute acquired concomitant esotropia (AACE) is a rare, distinct subtype of esotropia. The purpose of this retrospective study was to describe the clinical characteristics and discuss the classification and etiology of AACE.Charts from 47 patients with AACE referred to our institute between October 2010 and November 2014 were reviewed. All participants underwent a complete medical history, ophthalmologic and orthoptic examinations, and brain and orbital imaging.Mean age at onset was 26.6 ± 12.2 years. Of the 18 cases with deviations ≤ 20 PD, 16 presented with diplopia at distance and fusion at near vision at the onset of deviation; differences between distance and near deviations were < 8 PD; all cases except one were treated with prism and diplopia resolved. Of the 29 cases with deviations > 20 PD, 5 were mild hypermetropic with age at onset between 5 and 19 years, 16 were myopic, and 8 were emmetropic with age at onset > 12 years; 24 were surgically treated and 5 cases remained under observation; all 24 cases achieved normal retinal correspondence or fusion or stereopsis on postoperative day 1 in synoptophore; in 23 cases diplopia or visual confusion resolved postoperatively. Of the 47 cases, brain and orbital imaging in 2 cases revealed a tumor in the cerebellopontine angle and 1 case involved spinocerebellar ataxia as revealed by genetic testing.AACE in this study was characterized by a sudden onset of concomitant nonaccommodative esotropia with diplopia or visual confusion at 5 years of age or older and the potential for normal binocular vision. We suggest that AACE can be divided into 2 subgroups consisting of patients with relatively small versus large angle deviations. Coexisting or underlying neurological diseases were infrequent in AACE.     

中国老年人日常生活活动能力损失现况及影响因素分析

目的 分析中国老年人日常生活活动能力现况及影响因素，探讨有效维持及提高老年人日常生活活动能力的方向。方法 利用中国健康与养老追踪调查2013年全国追访调查数据，收集中国≥60岁老年人社会人口学特征以及日常生活活动情况。以洗澡、进食、上下床、穿衣、如厕、排便6个项目评估基本日常生活活动能力（ADL）；以做家务、做饭、使用电话、服药、购物、理财6个项目评价工具性日常生活活动能力（IADL）。使用χ²检验比较不同人群ADL和IADL损失情况的差别，采用logistic回归分析老年人ADL和IADL损失的影响因素。结果 中国老年人的ADL损失率为23.8%、IADL损失率为35.4%；ADL损失率排前3位的项目依次为如厕、洗澡和上下床；IADL损失率排前3位的项目依次为使用电话、做家务、理财。女性、年龄越大、文化程度越低、居住在中西部地区、患慢性病种类越多、残疾的老年人其ADL和IADL损失的可能性均更高；离婚或分居、丧偶的老年人更可能ADL损失，农业户口的老年人更可能IADL损失。结论 应采取综合性防治措施延缓或减轻中国老年人日常生活活动能力的损失，同时为日常生活行为能力损失的老年人提供及时、适宜的照料。     

Nonadiabatic coupling of the dynamical structure to the superconductivity in YSr2Cu2.75Mo0.25O7.54 and Sr2CuO3.3

A crucial issue in cuprates is the extent and mechanism of the coupling of the lattice to the electrons and the superconductivity. Here we report Cu K edge extended X-ray absorption fine structure measurements elucidating the internal quantum tunneling polaron (iqtp) component of the dynamical structure in two heavily overdoped superconducting cuprate compounds, tetragonal YSr₂Cu_2.75Mo_0.25O_7.54 with superconducting critical temperature, T_c = 84 K and hole density p = 0.3 to 0.5 per planar Cu, and the tetragonal phase of Sr₂CuO_3.3 with T_c = 95 K and p = 0.6. In YSr₂Cu_2.75Mo_0.25O_7.54 changes in the Cu-apical O two-site distribution reflect a sequential renormalization of the double-well potential of this site beginning at T_c, with the energy difference between the two minima increasing by ∼6 meV between T_c and 52 K. Sr₂CuO_3.3 undergoes a radically larger transformation at T_c, >1-Å displacements of the apical O atoms. The principal feature of the dynamical structure underlying these transformations is the strongly anharmonic oscillation of the apical O atoms in a double-well potential that results in the observation of two distinct O sites whose Cu–O distances indicate different bonding modes and valence-charge distributions. The coupling of the superconductivity to the iqtp that originates in this nonadiabatic coupling between the electrons and lattice demonstrates an important role for the dynamical structure whereby pairing occurs even in a system where displacements of the atoms that are part of the transition are sufficiently large to alter the Fermi surface. The synchronization and dynamic coherence of the iqtps resulting from the strong interactions within a crystal would be expected to influence this process.

More than 30 y after the discovery of unconventional superconductivity in cuprates (1) and subsequently in analogous materials its underlying mechanism and in particular the role of the lattice are still under debate. Proposed microscopic theories range from purely electronic Mott–Hubbard and t-J approaches at one extreme to Bose–Einstein condensates of bipolarons at the other (2–4). Experimentally, however, anomalous isotope effects (5), resonant ultrasound (6), angle-resolved photoemission spectroscopy (7–9), femtosecond optical pump terahertz (10)/megaelectron-volt transmission electron microscopy probe (11), infrared pump (12), and so on have demonstrated that specific phonons not only couple to the superconductivity but correlate directly with the gap energy and may even transiently induce it well above the superconducting critical temperature, T_c. Cuprates also exhibit a plethora of superstructures indicative of strong electron–lattice coupling, stripes that have been proposed to stabilize the superconductivity (13), and charge-density waves (14, 15) and the pseudogap (PG) (16) that compete with it. Another possibility is mechanisms that boost T_c from a low value expected within a conventional Bardeen-Cooper-Schrieffer (BCS) scheme. That this question remains unanswered suggests considering more unconventional approaches (4). One candidate is the dynamical structures of cuprates, S(Q, E) or experimentally S(Q, t = 0), specifically their internal quantum tunneling polarons (iqtp). An iqtp is a set of atoms oscillating between two structures that possess different geometries, energy levels, and charge distributions (17–19). A chemist would describe these endpoints as separate species, adapting this term that applies more intuitively to solutions to the atoms in crystalline solids. Neutron scattering and X-ray absorption fine structure (XAFS) measurements identified O-centered iqtps and their correlation with the superconductivity 30 y ago (17–25). We now present Cu K edge extended XAFS (EXAFS) results from “overdoped” YSr₂Cu_2.75Mo_0.25O_7.54 (YSCO-Mo) that is isostructural with YBa₂Cu₃O₇ (Fig. 1A and SI Appendix, Fig. S1), T_c = 84 K (26) and hole doping p (excess charge on the planar Cu2 site) = 0.3 to 0.5 (27) and Sr₂CuO_3.3 (SCO) that is structurally analogous to La₂CuO₄ (Fig. 1B and SI Appendix, Fig. S1), T_c = 95 K (28, 29), and p = 0.6, both synthesized via high-pressure oxygenation (HPO) (30, 31). In YSCO-Mo the Cu2-apical O (Oap) double-well potential is degenerate in the normal state but renormalizes below T_c with the energy difference between its two minima increasing with decreasing temperature by ∼6 meV. SCO is already unique among cuprates in not having intact CuO₂ planes (32, 33). Its Cu EXAFS demonstrate that it is unique among superconductors in that its Oap shift by >1 Å at its superconducting transition, challenging our conception of superconductivity as an electronic transition that is incompatible with structural transformations.Open in a separate windowFig. 1.Structures and modulus and real components of the Fourier transforms of the EXAFS spectra, χ(R), of YSCO-Mo and SCO across temperature ranges bracketing their superconducting transitions. (A) Structure representation of YSCO-Mo. The CuO₂ planes are turqoise (Cu2) and magenta (Opl), Cu-O chains are blue (Cu1) and gold (Och), Oap is red, and Sr is green. In the actual structure one-fourth of Cu1 are substituted by Mo. The orientation is shown underneath. (B) The same as A for SCO, except a significant number of Oap and half of the O sites in the a direction in the CuO₂ planes are vacant. The CuO₂ planes are blue (Cu) and gold (O). For the χ(R) spectra the blue traces denote the lowest temperatures, then green to yellow, purple, and red-orange to brown at the highest ones. (C) YSCO-Mo spectra for E of the X-ray probe beam in the aa plane, with the modulus peaks labeled with their principal sources. The first temperature above T_c is red. (D) YSCO-Mo spectra for E||c, with the Cu1- and Cu2-Oap contributions overlapping at R = 1.6 Å. The peaks at higher R are a combination of direct, two-leg path contributions from more distant neighbor atom shells and ordered multiple scattering paths. (E) SCO spectra for E||H used for the orientation that is assigned to the a direction of the orthorhombic O sublattice. T_c is red and double width. (F–I) SCO over the designated temperature ranges for E⊥H spectra that will be the contributions in the bc plane defined by the orthorhombic O sublattice. (F) The extent of the change in the spectra, and by inference in their originating structures, across the superconducting transition. The features appearing at R = 2 to 2.5 Å below T_c result from the ∼2 Å shift of the O depicted in Fig. 3 B–D. In G the first temperature above T_c is orange and double width.We have recently shown that HPO cuprates are described by their own phase diagram (34). The principal feature of the well-known one for non-HPO cuprates is the superconducting “dome” that begins at p ∼0.06, peaks at p ∼ 0.16, and ends at p ∼ 0.27. Subsequent augmentations with the microstrain in the planes (35) and hole density on the O atoms (36) explain some of the material specificity but do not modify this overall pattern. For HPO compounds the superconductivity may begin at p < 0.06 and continues to increase beyond p = 0.27 with possible flattening but no reduction in T_c. Although we have found that the excess O in YSCO-Mo is mostly taken up by domains enriched in octahedral Mo(VI) substituting in the Cu(1) chains, much of the extra charge resides in the CuO₂ planes (27) and some of the carriers constitute a normal Fermi liquid that coexists with the superconductivity (26). The inherent inhomogeneity (37) in YSCO-Mo and SCO was probed by EXAFS, which is arguably the most incisive experimental method for characterizing short-range order and is especially sensitive to its changes. Diffraction patterns originate in the long-range average structure of a material and provide precise information on the symmetry and symmetry-constrained locations of the atoms that dominate the Bragg peaks. In contrast, EXAFS—and pair distribution function (pdf) analysis—are sensitive to local order separate from the crystallographic symmetry. The element selectivity of EXAFS provides further advantages by separating the atom pairs comprising the distribution function. Especially important for this study, EXAFS measures the instantaneous structure factor, S(Q, t = 0), that incorporates the dynamic structure components, S(Q, E), observed with inelastic scattering. EXAFS therefore accesses time and energy scales corresponding to collective dynamical phenomena (25, 38, 39). Dynamical structures such as the iqtp are demonstrated when S(Q, E/t = 0) gives locations for atoms that differ from those (19, 38) obtained from diffraction and elastic scattering measurements (20–22, 40). This complementarity was the basis for the original identification of the Cu-Oap two-site distribution (41) and its assignment to the double-well potential of the iqtp (17, 19, 42).     

硼替佐米皮下注射方案治疗3例POEMS综合征并文献复习

目的:探讨含硼替佐米方案治疗POEMS综合征的有效性和安全性。方法:报道3例POEMS综合征经含硼替佐米方案治疗的过程及结果，并对相关文献进行复习。结果:3例病人经化疗后1例神经症状得到明显改善，1例腹胀症状消失，1例神经症状及胸闷、气短症状改善。结论:含硼替佐米方案治疗POEMS综合征患者取得了较好疗效，未出现神经毒副作用。     

A Phase I Trial of Trametinib in Combination with Sorafenib in Patients with Advanced Hepatocellular Cancer

Lessons Learned

• The combination of trametinib and sorafenib has an acceptable safety profile, albeit at doses lower than approved for monotherapy.
• Maximum tolerated dose is trametinib 1.5 mg daily and sorafenib 200 mg twice daily.
• The limited anticancer activity observed in this unselected patient population does not support further exploration of trametinib plus sorafenib in patients with hepatocellular carcinoma.

BackgroundThe RAS/RAF/MEK/ERK signaling pathway is associated with proliferation and progression of hepatocellular carcinoma (HCC). Preclinical data suggest that paradoxical activation of the MAPK pathway may be one of the resistance mechanisms of sorafenib; therefore, we evaluated trametinib plus sorafenib in HCC.MethodsThis was a phase I study with a 3+3 design in patients with treatment‐naïve advanced HCC. The primary objective was safety and tolerability. The secondary objective was clinical efficacy.ResultsA total of 17 patients were treated with three different doses of trametinib and sorafenib. Two patients experienced dose‐limiting toxicity, including grade 4 hypertension and grade 3 elevation of aspartate aminotransferase (AST)/alanine aminotransferase (ALT)/bilirubin over 7 days. Maximum tolerated dose was trametinib 1.5 mg daily and sorafenib 200 mg twice a day. The most common grade 3/4 treatment‐related adverse events were elevated AST (37%) and hypertension (24%). Among 11 evaluable patients, 7 (63.6%) had stable disease with no objective response. The median progression‐free survival (PFS) and overall survival (OS) were 3.7 and 7.8 months, respectively. Phosphorylated‐ERK was evaluated as a pharmacodynamic marker, and sorafenib plus trametinib inhibited phosphorylated‐ERK up to 98.1% (median: 81.2%) in peripheral blood mononuclear cells.ConclusionTrametinib and sorafenib can be safely administered up to trametinib 1.5 mg daily and sorafenib 200 mg twice a day with limited anticancer activity in advanced HCC.     

经自然腔道取标本手术在结直肠外科手术中的应用进展

随着腔镜技术的进一步发展以及微创理念应用于结直肠外科疾病的诊治中,结直肠相关疾病的诊治发生了翻天覆地的变化。由传统的经腹手术到腹腔镜手术、经自然腔道手术,再到经自然腔道取标本手术(NOSES),结直肠疾病的外科诊治在微创领域取得了巨大成果。NOSES技术是目前结直肠外科在微创领域前沿的手术方式之一,它通过经直肠、阴道取标本来避免了腹壁的辅助取标本切口,从而将结直肠外科手术进一步微创化。NOSES技术集传统腹腔镜手术的优势与现代微创外科的理念于一体,它在确保手术效果的基础上集中体现了微创、加速康复外科、功能外科、"无疤"等理念的特点。本文主要就国内外各中心开展NOSES技术在结直肠外科诊治开展中的相关经验、心得和体会进行综述。     

经桡动脉途径行外周血管介入的临床研究

目的评价经桡动脉途径(TRA)行外周血管介入的安全性和可行性。方法回顾性收集2017年9月至2019年3月于中国医学科学院肿瘤医院TRA行外周血管介入治疗的106例肿瘤患者的临床资料,分析患者的桡动脉穿刺率、穿刺完成后续操作的手术成功率以及术后30 d内相关并发症。结果106例患者中,TRA外周血管介入操作112例次,其中行经导管肝动脉化疗栓塞术83例次,支气管动脉灌注术4例次,盆腔肿瘤栓塞术11例次,其他手术14例次。所有介入操作穿刺成功率为97.3%(109/112),手术成功率为98.2%(107/109)。5例患者TRA失败,转为股动脉穿刺,并顺利完成操作。手术严重并发症为主动脉夹层2例次;轻微并发症中,桡动脉闭塞2例次,桡动脉痉挛1例次,手臂疼痛1例次,穿刺点血肿1例次。严重并发症和轻微并发症发生率分别为1.8%(2/112)和4.5%(5/112)。急诊操作16例次,均顺利完成操作,无并发症发生。结论TRA行外周血管介入治疗是安全、可行的。     

Assessment of extravascular lung water by measuring the number of pulmonary ultrasound B-lines before and after CBP in patients with MODS

To determine whether the change in the number of pulmonary ultrasound B-line can accurately assess the extravascular lung water (EVLW) before and after continuous bedside blood purification (CBP) in patients with multiple organ dysfunction syndrome (MODS).Seventy-six patients with MODS who underwent CBP were examined within 24 hours before and after CBP using pulmonary ultrasound to detect the number of ultrasound B-line or using pulse indicator continuous cardiac output method to examine extravascular lung water, blood oxygenation index, and B-type natriuretic peptide (BNP) content. The correlation of the change in the number of B lines before and after CBP treatment with the negative balance of 24 hours liquid, the change of oxygenation index, and BNP content were analyzed.In the 76 patients, CBP treatment significantly decreased EVLW, the number of B-line, and BNP (P < .05 for all), while it significantly increased the oxygenation index (P < .05). Correlation analysis showed that the decrease in B-line number after CBP treatment was positively correlated with the 24 hours negative lung fluid balance, decrease of EVLW, oxygenation index improvement, and decreased BNP content. The change in the numbers of pulmonary ultrasound B-line can accurately assess the change of EVLW before and after CBP treatment and reflect the efficiency of ventilation in the lungs and the risk of heart failure.Thus, it can replace pulse indicator continuous cardiac output as an indicator for evaluating EVLW in patients with MODS treated with CBP.