干扰素致甲状腺功能异常1例

1.病例资料:患者男性,37岁,汉族,北京籍,教师.因"发现ALT升高5年,间断心悸1年余"就诊.患者5年前劳累后感觉乏力,检查结果显示:ALT 67 U/L、抗-HCV阳性.1年半前HCV RNA水平为2.8×10(5)拷贝/ml,并开始干扰素α-2b 3 MU/d治疗,未服用利巴韦林;治疗3个月时查HCV RNA低于检测限.     

大剂量干扰素治疗原发性无应答慢性丙型肝炎1例

1.病例资料:患者男性,22岁,汉族,职员.主因"反复肝功能异常4年"入院.患者4年前体检发现肝功能异常,ALT 126 U/L,无明显不适.在本院门诊检查抗-HCV阳性、HCV RNA阳性,诊断为慢性内型肝炎.因患者拒绝抗病毒治疗,故仅给予普通保肝、降酶治疗,1个月后ALT恢复正常.此后定期复查,ALT在正常～100 U/L之间波动.2年前检查结果显示:ALT 511 U/L、AST 226 U/L、总胆红素(TBil)28 μmol/L,住院治疗.     

I型糖尿病合并慢性丙型肝炎抗病毒治疗1例

1病例资料患者,女,29岁,BMI 19.1。24年前诊断为Ⅰ型糖尿病,3年前妊娠体检发现丙型肝炎抗体（HCV IgG阳性。产后42 d复诊查丙型肝炎病毒基因型为1b,HCV RNA 8.6×105IU/ml。肝功能：ALT 181.3 U/L,AST 266.6 U/L,TBil 8.8μmol/L,Alb 42.2 g/L;     

聚乙二醇干扰素联合利巴韦林治疗慢性丙型肝炎过程中出现听力障碍2例

一、病例资料病例l:女性患者,53岁,因发现抗-HCV阳性3年,间断乏力伴恶心、食欲减退3个月,于2009年4月16日入我院治疗.20年前行"左乳腺癌根治术",术中输血(具体量不详),否认耳部、甲状腺、自身免疫、血液系统及精神神经系统疾史.体格检查:血压120/80mm Hg(1 mm Hg=0.133kPa),皮肤、巩膜无黄染,可见肝掌,无蜘蛛痣,心、肺查体未见异常,腹平软,无压痛,肝脏、脾脏未触及.实验室检查:抗-HCV阳性,HCV RNA l.438x 106 IU/ml,HCV基因型Ib型;外周血白细胞计数(WBC) 5.2x 109/L,血小板计数139×109/L;血清ALT 42 U/L,AST 34 U/L.肝组织病理学检查:慢性丙型病毒性肝炎,G(1 -2) Sl,诊断为慢性丙型肝炎.     

肺癌术后并发急性重型丙型肝炎1例报告

正1病例资料患者男性,53岁,自由职业者。因"乏力、纳差1周"于2020年7月15日入住本院。患者1周前无明显诱因出现乏力、食欲减退,伴有恶心,无发热、呕吐、腹痛、腹泻等症状,7月8日于本院查血常规:WBC 4.22×10~9/L,PLT 101×10~9/L,RBC4.33×10~9/L,Hb 151 g/L;肝功能:Alb 40.4 g/L,ALT 1406 U/L,AST 726 U/L,TBil 22.9μmol/L;凝血系列:PTA 82%,INR 1.03;甲型肝炎抗体IgM阴性;戊型肝炎抗体IgM阴性;乙型肝炎五项抗-HBs、抗-HBe、抗-HBc阳性;丙型肝炎抗体定量0 C. O. I(参考值小于1.0 C. O. I),丙型肝炎核心抗原阳性;HCV RNA定量1.20×10~7IU/ml。     

干扰素联合利巴韦林治疗丙型肝炎并发结节性甲状腺肿1例

一、病例资料患者女性,44岁,1997年单位体检发现抗丙型肝炎病毒 (HCV)阳性,2004年12月复查肝功能,丙氨酸氨基转移酶 (ALT)108 U／L,天冬氨酸氨基转移酶(AST)89 U／L；2005 年3月底轻度乏力,化验检查：ALT 46 U／L,AST 46U／L, 凝血酶原时间(PT)13s,凝血酶原活动度(PTA)93％,抗- HCV阳性,HCV RNA 6．85×10~6拷贝／ml,HCV RNA未分出型,B超提示慢性肝损害,诊断为慢性丙型肝炎。化验检查甲状腺功能五项均正常,自身抗体阴性。2005年4月14日开始皮下注射长效α干扰素50μg(美国先灵葆雅公司产品),每周1次；利巴韦林0．4g,2次／d,口服。用药2周后复查肝功能正常,HCV RNA阴转(＜10~3拷贝／ml),甲状腺功能正常,出院。出院后在当地医院定期复查,每2周复查血常规,每月复查肝功能均为正常,未复查甲状腺功能。2005年8月初明     

直接抗病毒药物治疗儿童丙型肝炎1例报告

<正>1病例资料患儿男性,5岁,主诉"体检发现丙型肝炎抗体阳性2年"于2017年8月23日入本院。患儿2年前体检发现抗-HCV阳性,当时无纳差、乏力、腹胀、恶心等不适,未治疗,定期每6个月于本院门诊复查。2017年8月10日于本院门诊随诊检查肝功能:ALT 37 U/L,AST 47 U/L,HCV RNA:2 954 969 IU/ml(采用实时荧光定量PCR,Abbott m2000全自动核酸检测仪,雅培原     

聚乙二醇化干扰素α-2a治疗慢性乙型肝炎出现HBsAg血清转换后复发一例

患者,男性,33岁,因"乏力、四肢酸软2周"于2005年9月18日入院.患者2002年3月生化检查丙氨酸氨基转移酶(ALT)52 U/L,总胆红素(TBil)正常,乙型肝炎标志物:HBsAg、HBeAg和抗HBc阳性,HBV DNA定量4.6×107拷贝/ml,予保肝、降酶等治疗,ALT波动于50～210 U/L.2004年3月予聚乙二醇化干扰素α-2a(哌罗欣)抗病毒治疗,基线HBV DNA定量7×107拷贝/ml,SB 14 μmol/L,ALT176 U/L,白蛋白42 g/L,凝血酶原时间(PT)14 s,血常规:白细胞4.6×109/L,血小板127×109/L,血红蛋白143 g/L.     

干扰素a-2b治疗慢性丙型肝炎致白发1例

一、病例资料患者女性,30岁,布依族,农民,体质量50kg.体检结果显示抗-HCV阳性(酶联免疫吸附试验法),无明显肝病症状及体征;进一步检查提示:肝功能指标正常,HCVRNA阳性,为9.50×105拷贝/ml(最低检测限为1000拷贝/ nl),10年前曾因产后大出血接受过500 ml输血治疗;回顾性调查证实献血员为HCV感染者,病毒基因型为1b型;诊断为慢性丙型肝炎.在知情同意的基础上给予干扰素α-2b(购自天津华利达生物有限公司)3 MU,上臂三角肌处皮下注射,隔日1次;同时给予利巴韦林300 mg口服,2次/d;共治疗48周.治疗12周复查,HCV RNA阴性(＜1000拷贝/ml),提示患者获得早期病毒学应答;治疗24、36、48周及停药后24、48周复查,HCV RNA均阴性(最低检测限＜ 15 IU/ml),提示患者获得治疗结束时病毒学应答及持续病毒学应答.     

乙型肝炎肝硬化合并横纹肌溶解症1例报告

<正>1病例资料患者男性,49岁,因"发现HBs Ag阳性20年,腹胀、乏力2月余"于2013年1月25日于本院住院治疗。患者1993年查体发现HBs Ag阳性,2012年11月于外院就诊化验肝功能:ALT 36U/L,AST 47 U/L,TBil 18.4μmol/L;乙型肝炎抗原抗体五项:HBs Ag、抗-HBc阳性,HBV DNA 1.27×105IU/ml;腹部B超提示"肝     

Ochronosis: a report of a case and a review of literature

A patient with alkaptonuria and ochronotic pigment deposited in articular cartilage and sclerae clinically manifested a serious osteoarthritis of the peripheral and axial joints and synchondrosis, typically involved in long lasting cases of this hereditary defect of homogentisic acid oxidase. This is the first patient with this disorder reported, where a non-cemented total knee prosthesis (PCAR) was applied on both knees. This was possible due to the good quality of the bone stock, which did not seem to be impaired by ochronosis. Our patient had no cardiac symptoms or murmurs, but had a slight calcification in the annulus of aorta observed with echocardiography, a useful new method for screening this disease manifestation. A third new aspect reported is the immunopathology of the synovial tissue. Small pieces of torn-off cartilage were seen embedded in the synovial stroma. This was associated with a slight hyperplasia of the C3bi-receptor positive and proline hydroxylase positive type A and B synovial lining cells. Perivenular infiltrates contained CD2 positive T lymphocytes, mostly belonging to the CD4 subset, and some C3bi-receptor positive monocytes. Activated CD25 positive and immunoglobulin light chain positive T and B lymphocytes were absent or few. Because modern medicine has much to offer to those suffering from this ancient inborn error of metabolism in the form of new specific diagnostic methods and new surgical modes of treatment, such as endoprosthesis surgery and cardiac valve replacement, we also present a literature overview of this interesting condition.     

Charge of a quasiparticle in a superconductor

Nonlinear charge transport in superconductor–insulator–superconductor (SIS) Josephson junctions has a unique signature in the shuttled charge quantum between the two superconductors. In the zero-bias limit Cooper pairs, each with twice the electron charge, carry the Josephson current. An applied bias V_SD leads to multiple Andreev reflections (MAR), which in the limit of weak tunneling probability should lead to integer multiples of the electron charge ne traversing the junction, with n integer larger than 2Δ/eV_SD and Δ the superconducting order parameter. Exceptionally, just above the gap eV_SD ≥ 2Δ, with Andreev reflections suppressed, one would expect the current to be carried by partitioned quasiparticles, each with energy-dependent charge, being a superposition of an electron and a hole. Using shot-noise measurements in an SIS junction induced in an InAs nanowire (with noise proportional to the partitioned charge), we first observed quantization of the partitioned charge q = e*/e = n, with n = 1–4, thus reaffirming the validity of our charge interpretation. Concentrating next on the bias region eV_SD ～ 2Δ, we found a reproducible and clear dip in the extracted charge to q? ～ 0.6, which, after excluding other possibilities, we attribute to the partitioned quasiparticle charge. Such dip is supported by numerical simulations of our SIS structure.Excitations in superconductors (Bogoliubov quasiparticles) can be described according to the Bardeen–Cooper–Schrieffer (BCS) theory (1) as an energy-dependent superposition of an electron with amplitude u(ε), and a hole with amplitude v(ε), where the energy ε is measured relative to the Fermi energy (2). Evidently, the expectation value of the charge operator (applied to the quasiparticle wave function), which we address as the quasiparticle charge e* = q(ε)e, is smaller than the charge of an electron, q(ε) = |u(ε)|² ? |ν(ε)|² (3). Solving the Bogoliubov–de Gennes equations, one finds that |u(ε)|2=1/2[1+(ε2−Δ2/ε)] and |v(ε)|2=1/2[1−(ε2−Δ2/ε)], with the expected charge evolving with energy according to q(ε)=ε2−Δ2/ε––vanishing altogether at the superconductor gap edges (3). Note, however, that the quasiparticle wave function is not an eigenfunction of the charge operator (3, 4). Properties of quasiparticles, such as the excitation spectra (5), lifetime (6–10), trapping (11), and capturing by Andreev bound states (12, 13), had already been studied extensively; however, studies of their charge are lagging. In the following we present sensitive shot-noise measurements in a Josephson junction, resulting in a clear observation of the quasiparticle charge being smaller than e, q(eV_SD∼2Δ) < 1, and evolving with energy, as expected from the BCS theory.To observe the BCS quasiparticles in transport we study a superconductor–insulator–superconductor (SIS) Josephson junction in the nonlinear regime. The overlap between the wave functions of the quasiparticles in the source and in the drain is expected to result in a tunneling current of their effective charge. This is in contrast with systems which are incoherent (14, 15) or with an isolated superconducting island, where charge conservation leads to traversal of multiples of e – Coulomb charge (16). As current transport in the nonlinear regime results from “multiple Andreev reflections” (MAR), it is prudent to make our measurements credible by first measuring the charge in this familiar regime.In short, the MAR process, described schematically in Fig. 1, carries a signature of the shuttled charge between the two superconductors (SCs), being a consequence of n traversals through the junction (as electron-like and hole-like quasiparticles), with n an integer larger than 2Δ/eV_SD. A low transmission probability t (via tunneling through a barrier) in the bias range 2Δ/n < eV_SD < 2Δ/(n ? 1) assures dominance of the lowest order MAR process (higher orders are suppressed as tⁿ), with the charge evolving in nearly integer multiples of the electron charge. Although there is already a substantial body of theoretical (3, 17–23) and experimental (24–29) studies of the MAR process, charge determination without adjustable parameters is still missing. An important work by Cron et al. (27) indeed showed a staircase-like behavior of the charge using “metallic break junctions;” however, limited sensitivity and the presence of numerous conductance channels some of which with relatively high transmission probabilities did not allow exact charge quantization. Our shot-noise measurements, performed on a quasi-1D Josephson junction (single-mode nanowire) allowed clear observation of charge quantization without adjustable parameters. To count a few advantages: (i) the transmission of the SIS junction could be accurately controlled using a back-gate; (ii) this, along with our high sensitivity in noise measurements, enabled us to pinch the junction strongly (thus suppressing higher MAR orders); and (iii) with the Fermi level located near the 1D channel van Hove singularity, a rather monoenergetic distribution could be injected (SI Appendix, section S7).Open in a separate windowFig. 1.MAR. Illustrations of the leading processes contributing to the current as function of bias. In general, for 2Δ/(n ? 1) > eV_SD > 2Δ/n the leading charge contribution to the current is ne. An electron-like quasiparticle is denoted by a full circle, whereas a hole-like quasiparticle is denoted by an empty circle. (A) When the bias is larger than the energy gap, eV_SD > 2Δ, the leading process is a single-path tunneling of single quasiparticles from the full states (Left) to the empty states (Right). This current is proportional to the transmission coefficient t. Higher-order MAR process (dashed box), being responsible for tunneling of Cooper pairs, is suppressed as t². (B) For 2Δ > eV_SD > Δ, the main charge contributing to the current is 2e with probability t². (C) For Δ > eV_SD > 2Δ/3, the main charge contributing to the current is 3e with probability t³.     

Report of a case of a giant phytobezoar in a patient with a duodenal bulb ulcer.

A case of a large phytobezoar (750 g weight and with the length of 29 cm) due to Khormalou (Persimmon) is being reported in a young patient with chief complaint of abdominal pains and concomitant duodenal ulcer. Review of the literature in this subject shows that bezoars of this size and weight are relatively rare in healthy individuals.     

Fate of a mutation in a fluctuating environment

Natural environments are never truly constant, but the evolutionary implications of temporally varying selection pressures remain poorly understood. Here we investigate how the fate of a new mutation in a fluctuating environment depends on the dynamics of environmental variation and on the selective pressures in each condition. We find that even when a mutation experiences many environmental epochs before fixing or going extinct, its fate is not necessarily determined by its time-averaged selective effect. Instead, environmental variability reduces the efficiency of selection across a broad parameter regime, rendering selection unable to distinguish between mutations that are substantially beneficial and substantially deleterious on average. Temporal fluctuations can also dramatically increase fixation probabilities, often making the details of these fluctuations more important than the average selection pressures acting on each new mutation. For example, mutations that result in a trade-off between conditions but are strongly deleterious on average can nevertheless be more likely to fix than mutations that are always neutral or beneficial. These effects can have important implications for patterns of molecular evolution in variable environments, and they suggest that it may often be difficult for populations to maintain specialist traits, even when their loss leads to a decline in time-averaged fitness.Evolutionary trade-offs are widespread: Adaptation to one environment often leads to costs in other conditions. For example, drug resistance mutations often carry a cost when the dosage of the drug decays (1), and seasonal variations in climate can differentially select for certain alleles in the summer or winter (2). Similarly, laboratory adaptation to specific temperatures (3, 4) or particular nutrient sources (5, 6) often leads to declines in fitness in other conditions. Related trade-offs apply to any specialist phenotype or regulatory system that incurs a general cost to confer benefits in specific environmental conditions (7). Despite the ubiquity of these trade-offs, it is not always easy to predict when a specialist phenotype can evolve and persist. How useful must a trait be on average to be maintained? How regularly does it need to be useful? How much easier is it to maintain in a larger population compared with a smaller one?The answers to these questions depend on two major factors. First, how often do new mutations create or destroy a specialist phenotype, and what are their typical costs and benefits across environmental conditions? This is fundamentally an empirical question, which depends on the costs and benefits of the trait in question, as well as its genetic architecture (e.g., the target size for loss-of-function mutations that disable a regulatory system). In this paper, we focus instead on the second major factor: given that a particular mutation occurs, how does its long-term fate depend on its fitness in each condition and on the details of the environmental fluctuations?To address this question, we must analyze the fixation probability of a new mutation that experiences a time-varying selection pressure. This is a classic problem in population genetics, and has been studied by a number of previous authors. The effects of temporal fluctuations are simplest to understand when the timescales of environmental and evolutionary change are very different. For example, when the environment changes more slowly than the fixation time of a typical mutation, its fate will be entirely determined by the environment in which it arose (8). On the other hand, if environmental changes are sufficiently rapid, then the fixation probability of a mutation will be determined by its time-averaged fitness effect (9, 10). In these extreme limits, the environment can have a profound impact on the fixation probability of a new mutation, but the fluctuations themselves play a relatively minor role. In both cases, the effects of temporal variation can be captured by defining a constant effective selection pressure, which averages over the environmental conditions that the mutation experiences during its lifetime. This result is the major reason why temporally varying selection pressures are neglected throughout much of population genetics, despite the fact that truly constant environments are rare.However, this simple result is crucially dependent on the assumption that environmental changes are much slower or much faster than all evolutionary processes. When these timescales start to overlap, environmental fluctuations can have important qualitative implications that cannot be summarized by any effective selection pressure, even when a mutation experiences many environmental epochs over its lifetime. As we will show below, this situation is not an unusual special case, but a broad regime that becomes increasingly relevant in large populations. In this regime, the fate of each mutation depends critically on its fitness in each environment, the dynamics of environmental changes, and the population size.Certain aspects of this process have been analyzed in earlier studies. Much of this earlier work focuses on the dynamics of a mutation in an infinite population (11–24). However, these infinite-population approaches are fundamentally unsuitable for analyzing the fixation probabilities of mutations that are neutral or deleterious on average (and even for mutations that are beneficial on average, population sizes must often be unrealistically large for this infinite population size approximation to hold). Another class of work has focused explicitly on finite populations, but only in the case where the environment varies stochastically from one generation to the next (25–31). Later work has extended this analysis to fluctuations on somewhat longer timescales, but this work is still restricted to the special case where selection cannot change allele frequencies significantly during an individual environmental epoch (9, 32, 33).These studies have provided important qualitative insights into various aspects of environmental fluctuations. However, we still lack both a quantitative and conceptual understanding of more significant fluctuations, where selection in each environment can lead to measurable changes in allele frequency. This gap is particularly relevant because significant changes in allele frequency are the most clearly observable signal of variable selection in natural populations.In this work, we analyze the fate of a new mutation that arises in an environment that fluctuates between two conditions either deterministically or stochastically on any timescale. We provide a full analysis of the fixation probability of a mutation when evolutionary and environmental timescales are comparable and allele frequencies can change significantly in each epoch. We find that even in enormous populations, natural selection is often very inefficient at distinguishing between mutations that are beneficial and deleterious on average. In addition, substitution rates of all mutations are dramatically increased by variable selection pressures. This can lead to counterintuitive results. For instance, mutations that result in a trade-off but are predominantly deleterious during their lifetime can be much more likely to fix than mutations that are always neutral or even beneficial. Thus, it may often be difficult for populations to maintain specialist traits, even when loss-of-function mutations are selected against on average. This can lead to important signatures on the genetic level, e.g., in elevated rates of nonsynonymous to synonymous substitutions (dN/dS) (34).     

Hemoptysis in a patient with a previous surgical correction of a tetralogy of Fallot

Aorto-bronchial fistula is a rare but associated with a height rare of mortality. Although most reported cases are secondary to infectious aneurysms, cases arising after surgery to correct congenital cardiovascular abnormalities have recently been described. We report the case of a 41-year-old patient with recurrent hemoptysis and a history of Fallot's tetralogy corrected in childhood. Given such a case of hemoptysis in a patient with a history of cardiovascular surgery, the correct diagnostic approach includes fiberoptic bronchoscopy, helicoidal CAT and/or NMR, and aortography. Diagnostic confirmation should be followed soon by corrective surgery.