免疫球蛋白G4相关性疾病冠状动脉炎性假瘤1例

1 病例资料 患者,男性,58岁,2006年因"间断腹痛8年,体重下降2个月"入院,表现为劳累后出现上腹部胀满和疼痛不适,伴纳差、反复口腔溃疡、双眼睑肿胀.入院后腹部超声提示胰腺体尾部直径3.0 cm占位性病变.PET-CT:胰腺体尾部萎缩,胰头及钩突部饱满,未见明确异常代谢增高改变.血清IgG4测定 401.0 mg...     

小细胞肺癌胰腺转移一例

原发性肺癌发生胰腺转移的几率相对较小。现将我科收治的1例小细胞肺癌胰腺转移病例，报告如下。 临床资料 患者，男性，71岁。有长期吸烟史。入院前3周出现中上腹闷胀伴恶心、嗝气、食欲下降，1个月内体重下降约20余斤。上腹部CT检查提示胰尾部恶性占位伴双侧肾上腺转移，外院拟“胰腺癌”收入院行姑息治疗。     

肝动脉起源于肠系膜上动脉的改良Appleby手术1例报告

1病例资料患者女性,60岁,因“体检发现胰腺占位3 d”于2018年6月18日入本院。入院后查肿瘤指标:CA19-9403.90 U/ml;增强CT提示:胰腺尾部萎缩,体部见结节影,大小约19 mm×28 mm,考虑胰腺癌,侵犯腹腔干(celiac axis,CA)、脾动脉可能(图1)。     

胰腺实性-囊性-乳头状肿瘤的临床病理特征及鉴别诊断(附1例报告)

胰腺实性 -囊性 -乳头状肿瘤 ( SCPN )极少见 ,自 195 9年首次报告以来 ,至今世界上仅有 15 0余例报道 ,其约占胰腺非内分泌肿瘤的 0 .17%～ 2 .7% ,至今组织学来源尚未确定。2 0 0 1年 11月我们收治 SCPN患者 1例 ,现结合文献对其病理特征、临床特征及鉴别诊断进行讨论。患者女 ,18岁。因上腹疼痛 5天入院。查体 :左上腹可触及一拳头大小肿物 ,有压痛。CT检查 :见胰尾部有一 9.2 cm×7.2 cm类圆形软组织块影 ,边界尚清 ,密度不均。入院后第 3天在硬膜外麻醉下行脾及胰体尾切除术。术中见胰尾部有一约 10 cm× 9cm肿物 ,质软 ,与周围有…     

胰腺假性囊肿致区域性门脉高压伴上消化道出血一例

患者男,34岁.2007年2月因"上腹痛15 h"入院.体检:上腹部有压痛.实验室检查示WBC 19.6×109/L,血淀粉酶U/L,血糖13.6 mmol/L,LDH 580 U/L,AST 366 U/L.腹部CT提示胰腺坏死及胰周大量渗液,Balthazar分类为E级.诊断为重症急性胰腺炎.入院后给予禁食、空肠营养、抑制胰腺分泌、抗感染等治疗后好转,于2007年4月出院.出院时复查腹部CT仍提示腹腔较多渗液,2个月后复查腹部CT提示胰腺巨大假性囊肿,其后患者辗转至多家医院就诊,未果.     

原发性十二指肠球部腺癌1例

1 病例报告 男,57岁。因反复黑便3个月,进行性消瘦1个月于1994-07-30入院。入院前33d外院内镜诊断十二指肠球部溃疡。给予抑酸、抗炎等药物治疗,效果不佳。入院后体检:消瘦,重度贫血外貌,锁骨上淋巴结不肿大。心肺未见异常。腹软,全腹无压痛,上腹偏右可扪及一边界不清,质较硬,大小约7cm×6cm的包块,包块固定,无明显压痛。肝脾肋下未触及,无腹水征。血红蛋白63g/L,大便潜血试验阳性,肝胆脾胰B超及胸片正常。外院CT提示:十二指肠球部占位性病变,肝胆脾胰及肺部未见占位性病变。复查内镜见:十二指肠球部后壁小弯侧有一个约3.5cm×4cm的溃疡样肿物,周边隆起,边界不平整,底部凹凸不平,覆盖有污秽苔,组织接触易出血。刷片细胞学检查发现癌细胞。手术治疗,术中见十二指肠球部至球后部有一6cm×5cm×2cm的肿块,质硬,侵及浆膜,与胰腺组织粘连,肿块中央有一3cm×4cm     

胰腺腺鳞癌的临床诊治分析

目的 总结胰腺腺鳞癌临床诊治经验,以提高对该病的认识和诊治水平.方法 对2002年7月至2008年6月我院收治的5例胰腺腺鳞癌患者的临床资料进行回顾性分析,并结合文献讨论.结果 本组5例胰腺腺鳞癌患者,其中男3例,女2例,平均年龄(64±18)岁.肿瘤位于胰头部者2例,位于胰体尾部者3例;行胰头十二指肠切除术1例,行胰体尾、脾脏切除术3例,行胆肠+胃肠双旁路内引流术并~(125)Ⅰ粒子植入1例.肿瘤平均长径4.5 em,1例侵犯胃后壁、十二指肠降部、门静脉,2例侵犯脾门处包膜,2例合并有神经、血管侵犯,1例伴有淋巴结转移.组织学特征为腺癌和鳞癌成分混杂在一起,呈浸润性生长.5例均获随访,3例死于肿瘤复发和肝转移,术后生存8.5～13.5个月,平均11.2个月,2例已生存6个月和56个月.结论 胰腺腺鳞癌好发年龄60岁左右,临床确诊较困难,恶性程度高,预后差,手术切除结合放、化疗的综合治疗可提高疗效.     

肝滤泡树突细胞肉瘤1例报告

<正>1 病例资料患者女性,41岁,因"体检发现肝占位性病变3 d"入本院。2015年10月8日患者曾在上海东方肝胆外科医院行肝尾状叶、胆囊切除术,术后未行任何放、化疗,术后病理回报提示倾向于原发性肝滤泡树突细胞肉瘤(follicular dendritic cell sarcoma, FDCS)。查体:专科情况未见异常。入院后完善相关检查,肝脏超声造影示:动脉造影剂迅速填充,快于周围肝实质,延迟相造影剂消退明显快于周围肝实质,     

胰尾部神经鞘瘤1例报告

<正>神经鞘瘤是一种很常见的周围神经系统良性肿瘤,发病部位可遍及全身,但是多以头、颈等部位常见,发生于胰腺的神经鞘瘤较为罕见,并且术前诊断存在一定的困难,对手术方式的选择有着很大的干扰性。1 病例资料患者男性,52岁,因“发现胰体尾部占位性病变2个月余”于2021年7月19日前来本院住院治疗;患者既往体健,否认高血压、糖尿病、心脏病等病史。入院后行腹部CT(图1)检查提示胰尾部低密度占位性病变,增强期可见轻度不均匀强化,     

胰腺腺鳞癌—附3例报告及文献复习

胰腺腺鳞癌(pancreatic adenosquamous carcinoma)属于外分泌胰腺的原发性上皮性肿瘤。文献散见于个例报道。临床经过凶险,预后差。本报告3例并结合文献复习,以提高对其认识。 例1:住院号:392310。男性,60岁。因上腹部饱胀疼痛1月,于2000年3月18日入院。1月前无明显诱因感上腹部饱胀疼痛,向腰背部放射。外院查CT提示胰头癌。病程中无发     

Overriding native cell coordination enhances external programming of collective cell migration

As collective cell migration is essential in biological processes spanning development, healing, and cancer progression, methods to externally program cell migration are of great value. However, problems can arise if the external commands compete with strong, preexisting collective behaviors in the tissue or system. We investigate this problem by applying a potent external migratory cue—electrical stimulation and electrotaxis—to primary mouse skin monolayers where we can tune cell–cell adhesion strength to modulate endogenous collectivity. Monolayers with high cell–cell adhesion showed strong natural coordination and resisted electrotactic control, with this conflict actively damaging the leading edge of the tissue. However, reducing preexisting coordination in the tissue by specifically inhibiting E-cadherin–dependent cell–cell adhesion, either by disrupting the formation of cell–cell junctions with E-cadherin–specific antibodies or rapidly dismantling E-cadherin junctions with calcium chelators, significantly improved controllability. Finally, we applied this paradigm of weakening existing coordination to improve control and demonstrate accelerated wound closure in vitro. These results are in keeping with those from diverse, noncellular systems and confirm that endogenous collectivity should be considered as a key quantitative design variable when optimizing external control of collective migration.

Collective cell migration enables intricate, coordinated processes that are essential to multicellular life, spanning embryonic development, self-healing upon injury, and cancer invasion modes (1). Control of collective cell migration, therefore, would be a powerful tool for biology and bioengineering as such control would enable fundamentally new ways of regulating these key processes, such as enabling accelerated wound healing. Efficient and precise control over cell motility is becoming increasingly feasible with modern biotechnologies. Tunable chemical gradient generators can redirect chemotaxing cells (2, 3), optogenetics can allow dynamic control of cell contractility (4), micropatterned scaffolds can constrain and direct collective growth (5), and recent work in bioelectric interfaces has even demonstrated truly programmable control over directed cell migration in two dimensions (6, 7). However, despite advances in sophisticated tools, applying them to complex cellular collectives raises a fundamental problem: What happens when we command a tissue to perform a collective behavior that competes with its natural collective behaviors?Paradoxically, those endogenous collective cell behaviors already present in tissues are both a boon and bane for attempts to control and program cell behavior. On the one hand, endogenous collective cell migration means the cells already have established mechanisms for coordinated, directional migration that external cues and control can leverage. For instance, cadherin-mediated cell–cell adhesions in tissues mechanically couple cells together and allow for long-range force transmission and coordinated motion. This coupling allows tissues to migrate collectively and directionally over large distances and maintain cohesion and organization far better than individual cells might (8, 9). On the other hand, imposing a new behavior over an existing collective behavior may generate conflicts. Tight cell coupling can create a “jammed state” or solid-like tissue where cells are so strongly attached and confined that they physically lack the fluidity to migrate as a group (10, 11). Strong coordination established via physical coupling can hinder cells from responding to signals for migration, as shown by the need for zebrafish and other embryos to weaken cell–cell junctions prior to gastrulation to ensure cells collectively migrate to necessary locations (12–14). Hence, how “susceptible” a collective system may be to external control likely depends on a tug-of-war between the resilience and strength of the natural collective processes and the potency of the applied stimulus.Here, we specifically investigate the relationship and interplay between an applied, external command attempting to direct collective cell migration and the strength of the underlying collective behaviors already present in the tissue. We address two key questions. 1) How much does the strength of an endogenous collective migration behavior in a tissue limit our ability to control its collective cell migration? 2) How can we circumvent such limitations? To investigate these questions, we needed both a programmable perturbation capable of controlling collective migration and a physiologically relevant model system allowing for tunable “collectivity.” Here, we use collectivity to describe how strongly cells are coordinated with their neighbors during migration—highly collective cells exhibit strong, coordinated motion and vice versa. As a perturbation, we harnessed a bioelectric phenomenon called “electrotaxis”—directed cell migration in direct current (DC) electric fields—using our SCHEEPDOG bioreactor (6). Briefly, electrotaxis arises when endogenous, ionic fields form during healing or development (∼1 V/cm) and apply gentle electrophoretic or electrokinetic forces to receptors and structures in cell membranes, causing them to aggregate or change conformation to produce a front–rear polarity cue (15, 16). Components spanning phosphatidylinositol phosphates (PIPs), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), phosphatase and tensin homolog (PTEN), and small guanosine triphosphate (GTP)ases have been implicated in the transduction process, while gap junctions appear to have an inconclusive role (8, 17–19). Crucially, electrotaxis may be one of the broadest and most conserved migratory cues, having been observed in vitro in over 20 cell types across multiple branches of the tree of life (20–22). As electrotaxis in vitro appears to globally stimulate all cells equally and still induce directional motion, it is distinct from more locally dependent cues such as chemotaxis and haptotaxis. However, as no other reported cue has as much versatility and programmability, electrotaxis is an ideal choice for a broadly applicable cellular control cue in this study.To complement electrotaxis, we chose primary mouse skin for our model system as skin injuries were where the endogenous electrochemical fields that cause electrotaxis were first discovered (in vivo, the wound boundary is negative relative to the surrounding epidermis), and we and others have shown layers of keratinocytes to exhibit strong electrotaxis (6, 23–25). Critically, primary mouse keratinocytes have tunable collectivity in culture as the cadherin-mediated cell–cell adhesion strength in this system can be easily tuned by varying calcium levels in the media—with low-calcium media thought to mimic conditions in the basal layers of the epidermis with weak adhesions and high-calcium media akin to conditions in the uppermost layers of skin with strong adhesions (26–28).Together, these experimental approaches allowed us to precisely explore how the ability to externally “steer” collective migration in a living tissue using a powerful bioelectric cue depends on the native collectivity of the underlying tissue. First, we quantify collective strength in cultured skin layers by measuring neighbor coordination of cellular motion [a standard metric for collective motion adapted from collective theory (29)] and then, validate that the collectivity can be tuned in our model system of mouse keratinocyte monolayers by calibrating junctional E-cadherin levels. Next, we demonstrate how applying the same electrical stimulation conditions to tissues with differing native collectivity results in radically different outputs, with weakly collective tissues precisely responding to our attempts to control their motion, while strongly collective tissues exhibited detrimental supracellular responses resulting in tissue collapse. We then prove that E-cadherin is responsible for these differences, ruling out any effects of calcium signaling per se. Finally, we leverage these findings to develop an approach that allows us to effectively control mature, strongly collective tissues, which we utilize to demonstrate that we can accelerate wound repair in vitro.     

Structure of cell–cell adhesion mediated by the Down syndrome cell adhesion molecule

The Down syndrome cell adhesion molecule (DSCAM) belongs to the immunoglobulin superfamily (IgSF) and plays important roles in neural development. It has a large ectodomain, including 10 Ig-like domains and 6 fibronectin III (FnIII) domains. Previous data have shown that DSCAM can mediate cell adhesion by forming homophilic dimers between cells and contributes to self-avoidance of neurites or neuronal tiling, which is important for neural network formation. However, the organization and assembly of DSCAM at cell adhesion interfaces has not been fully understood. Here we combine electron microscopy and other biophysical methods to characterize the structure of the DSCAM-mediated cell adhesion and generate three-dimensional views of the adhesion interfaces of DSCAM by electron tomography. The results show that mouse DSCAM forms a regular pattern at the adhesion interfaces. The Ig-like domains contribute to both trans homophilic interactions and cis assembly of the pattern, and the FnIII domains are crucial for the cis pattern formation as well as the interaction with the cell membrane. By contrast, no obvious assembly pattern is observed at the adhesion interfaces mediated by mouse DSCAML1 or Drosophila DSCAMs, suggesting the different structural roles and mechanisms of DSCAMs in mediating cell adhesion and neural network formation.

The Down syndrome cell adhesion molecule (DSCAM) was initially identified by isolating genes responsible for the phenotypes of Down syndrome (1), a genetic disease featured with cognitive and learning deficits (2). The DSCAM gene locates at the Down syndrome critical region (DSCR) on human chromosome 21 and is broadly expressed in nervous system (1, 3, 4), and its expression increases in patients with Down syndrome and in mouse models (3, 5, 6). Therefore, DSCAM has been hypothesized as a candidate gene associated with neurodevelopmental disorders and its dysregulation may lead to cognitive impairment and intellectual disability in Down syndrome (7), but the mechanism for the association between DSCAM and Down syndrome is still poorly understood.In invertebrates, Drosophila DSCAM1 (dDSCAM1) undergoes extensive alternative splicing by generating 38,016 isoforms with distinct recognition specificity (8–10), which is crucial for isoneuronal avoidance (11, 12). Loss of function or overexpression of dDSCAM1 in mutant flies causes defects or disorders in dendrite arborization (13, 14), axon guidance (15, 16), axon branching (17, 18), and synaptic targeting (11, 19, 20). Drosophila DSCAM2 (dDSCAM2) and DSCAM4 (dDSCAM4) also function in neural network formation by directing dendritic targeting but without the massive isoform diversity (21), and dDSCAM2 can mediate axonal tiling as well (22). Aplysia DSCAM (aDSCAM) is involved in transsynaptic protein localization (23).In vertebrates, two paralogous DSCAM genes, DSCAM and DSCAML1 (DSCAM-LIKE1) were identified (1, 24) and both of them could promote isoneuronal and homotypic self-avoidance (25, 26). In mouse, neurons expressing DSCAM (mDSCAM) or DSCAML1 (mDSCAML1) mutants may lose their mosaic pattern and neurite arborization (26, 27). Although the mechanism of mDSCAM-mediated self-avoidance remains unclear, it has been suggested that mDSCAM may function by masking the adhesion mediated by certain cadherin superfamily members (28). In addition, mDSCAM may also regulate neurite outgrowth (29, 30), promote cell death (31, 32), and control neuronal delamination (33). Studies have also shown that it could direct lamina-specific synaptic connections in chick (34) and be involved in cell movement in zebrafish (35). In contrast to dDSCAM1, the extensive alternative splicing has not been found for DSCAM in vertebrates, suggesting the different roles in the formation of neuronal circuits.DSCAM belongs to the immunoglobulin superfamily (IgSF) and consists of 10 immunoglobulin-like (Ig-like) domains, 6 type III fibronectin (FnIII) domains, a transmembrane domain, and a cytoplasmic domain (Fig. 1A). The domain arrangements of DSCAMs from invertebrates and vertebrates are quite similar, and the amino acid sequence identities of DSCAM among homologs are 98% between mDSCAM and hDSCAM (human), 59% between mDSCAM and mDSCAML1, and 33% between mDSCAM and dDSCAM1. The crystal structures of the N-terminal Ig-like domains of dDSCAM1 have been solved (36, 37). The eight N-terminal Ig-like domains form a dimer with a double-S–shaped conformation, which is critical for the homophilic cell adhesion (36). However, it is unclear whether the N-terminal Ig-like domains of mDSCAM and mDSCAML1 adopt a similar conformation to dDSCAM1, and the roles of other domains of DSCAM in cell adhesion remain elusive.Open in a separate windowFig. 1.Conformations of the ectodomains of mDSCAM, mDSCAML1, and dDSCAM1. (A) Diagrams of mDSCAM, mDSCAML1, and dDSCAM1 (ovals, Ig-like domains; rounded rectangles, FnIII domains; vertical rectangles, transmembrane domains; rectangles, cytoplasmic domains). (B–D) Negative staining EM images show the particles of mDSCAM-D_1–8, mDSCAM-D_9–16, and mDSCAM-D_1–16, respectively (Top, red arrows). (Scale bar, 50 nm.) The selected particles (Middle; the particles are picked from different images) and their contours (Bottom) are also listed. (Scale bar, 10 nm.) The schematic models of mDSCAM-D_1–8, mDSCAM-D_9–16, and mDSCAM-D_1–16 are shown in the Top Left Insets, respectively. (E–G) Negative staining EM images show the particles of mDSCAML1-D_1–8, mDSCAML1-D_9–16, and mDSCAML1-D_1–16, respectively (Top, red arrows). (Scale bar, 50 nm.) The selected particles (Middle) and their contours (Bottom) are also listed. (Scale bar, 10 nm.) The schematic models of mDSCAML1-D_1–8, mDSCAML1-D_9–16, and mDSCAML1-D_1–16 are shown in the Top Left Insets, respectively. (H–J) Negative staining EM images show the particles of dDSCAM1-D_1–8, dDSCAM1-D_9–16, and dDSCAM1-D_1–16, respectively (Top, red arrows). (Scale bar, 50 nm.) The selected particles (Middle) and their contours (Bottom) are also listed. (Scale bar, 10 nm.) The schematic models of dDSCAM1-D_1–8, dDSCAM1-D_9–16, and dDSCAM1-D_1–16 are shown in the Top Left Insets, respectively.Recently, electron tomography (ET) has become a powerful tool to provide three-dimensional (3D) views of biological samples (38, 39). By combining correlative light and electron microscopy (CLEM), high-pressure freezing and freeze substitution (HPF-FS), ultrathin sectioning and ET, the 3D structure of cellular or tissue samples can be reconstructed at nanometer resolution, revealing the molecular architecture of macromolecules in situ (40–43). Here we characterize the structures of mDSCAM, mDSCAML1, and dDSCAMs by electron microscopy (EM) as well as other biochemical and biophysical methods and reconstruct the 3D views of the mDSCAM-mediated adhesion interface by electron tomography, thereby unveiling the in situ structural model and the potential mechanism of cell adhesion by DSCAM.     

The gametic central cell of Arabidopsis determines the lifespan of adjacent accessory cells

Plant germ cells develop in specialized haploid structures, termed gametophytes. The female gametophyte patterns of flowering plants are diverse, with often unknown adaptive value. Here we present the Arabidopsis fiona mutant, which forms a female gametophyte that is structurally and functionally reminiscent of a phylogenetic distant female gametophyte. The respective changes include a modified reproductive behavior of one of the female germ cells (central cell) and an extended lifespan of three adjacent accessory cells (antipodals). FIONA encodes the cysteinyl t-RNA synthetase SYCO ARATH (SYCO), which is expressed and required in the central cell but not in the antipodals, suggesting that antipodal lifespan is controlled by the adjacent gamete. SYCO localizes to the mitochondria, and ultrastructural analysis of mutant central cells revealed that the protein is necessary for mitochondrial cristae integrity. Furthermore, a dominant ATP/ADP translocator caused mitochondrial cristae degeneration and extended antipodal lifespan when expressed in the central cell of wild-type plants. Notably, this construct did not affect antipodal lifespan when expressed in antipodals. Our results thus identify an unexpected noncell autonomous role for mitochondria in the regulation of cellular lifespan and provide a basis for the coordinated development of gametic and nongametic cells.     

Neutrophil–lymphocyte ratio as a prognostic factor for minute clear cell renal cell carcinoma diagnosed using multi-slice spiral CT

Minute clear cell renal cell carcinoma (MccRCC) has a diameter of <1.5 cm and can be diagnosed using multi-slice spiral CT (MSCT). Recently, the role of the neutrophil–lymphocyte ratio (NLR) in the development of MccRCC has attracted attention. This study aimed to further explore the relationship between the NLR and MccRCC.This was a prospective study of 100 patients who were diagnosed with MccRCC using MSCT at Urumqi Friendship Hospital, China. The study investigated a series of pretreatment factors, including NLR and patients’ general clinical data. Statistical methods employed included Pearson''s chi-square test, Spearman-rho correlation test, Cox regression analysis, and receiver operator characteristic curve analysis.Based on Pearson''s χ², Spearman-rho test, and univariate/multivariate Cox regression analysis, the overall survival of patients with MccRCC was shown to be significantly related to NLR (P < .001). NLR (hazard ratio = 50.676, 95%CI, 17.543–146.390, P < .001) is a significant independent risk-factor for MccRCC. A receiver operator characteristic curve was plotted to examine specificity and sensitivity between NLR and MccRCC (area under curve = 0.958, P < .001).The level of the NLR plays a crucial role in the survival of patients with MccRCC, as diagnosed with MSCT. The higher the NLR, the worse the prognosis for patients with MccRCC.     

肝卵圆细胞分化调控机制的研究进展

卵圆细胞是肝脏的干细胞，具备多向分化潜能，体内外实验证实其可以分化为肝细胞、胆管细胞、胰腺及肠型上皮细胞。在胚胎发育过程中，肝脏干细胞以肝细胞的形式存在，而在成年哺乳动物的肝组织中则以卵圆细胞的形式存在。对卵圆细胞分化调控机制的研究在基础理论和临床应用等方面均有重要意义，一方面，卯圆细胞可能参与肝脏损伤的修复与重建，研究其分化机制有助于阐明肝脏的发育机制；另一方面，卵圆细胞可分化为具有功能的成熟肝细胞，将为肝细胞移植和生物型人工肝提供重要的细胞来源，可能缓解供体肝脏严重缺乏的矛盾。但卵圆细胞的分化过程和机制非常复杂，分化异常可能导致肝细胞癌的发生。