Modifying the progression of Parkinson's disease through movement interventions:multimodal quantification of underlying mechanisms

Introduction:Parkinson’s disease(PD)is the most common neurodegenerative movement disorder.The pathological hallmark is the progressive loss of dopaminergic neurons of the substantia nigra pars compacta,which is accompanied by widespread alterations in the structu re and function of distributed brain networks.Togethe r,these processes cause a variety of motor symptoms such as bradykinesia,rigidity,tremor,gait disorders,or difficulties in fine motor control(Bange et al.,2022).

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

激光性角膜手术与眼内屈光手术矫治超高度近视眼

目的:评价及探讨矫治超高度近视眼的各类屈光手术的有效性、稳定性和安全性。方法:随机选择临床中观察到的超高度近视患者行各类屈光手术者108眼,近视范围-10.00～-24.50D,术前屈光度平均为(-12.25±1.53)D,散光平均为(-1.52±0.55)D;手术方式的选择:(1)I组52眼,行LASIK术:(2)II组23眼,行透明晶状体超声乳化摘除加后房型人工晶状体植入术。(3)III组33眼行有晶状体眼虹膜固定型人工晶状体植入术。术后随访观察平均6mo,主要观察术后裸眼视力、最佳矫正视力、屈光度、眼压及眼前段、眼底情况。结果:三组术后裸眼视力均比术前提高,术后裸眼视力≥0.5者分别是42眼(80.8%),20眼(87.0%),28眼(84.8%),术后屈光度分别为(-2.10±2.38)D,(-1.75±1.33)D,(0.83±1.16)D,主要并发症I组术后6mo黄斑出血1眼,II组术后15mo视网膜脱离1眼,III组平均角膜内皮细胞丢失率为4.5%。结论:对于超高度近视,晶状体性屈光手术效果优于LASIK术。对超高度近视行屈光手术,要根据患者年龄,眼部情况,手术医师的技术等,选择安全、有效、稳定性好的手术。

Significance of preoperative C-reactive protein as a parameter of the perioperative course and long-term prognosis in squamous cell carcinoma and adenocarcinoma of the oesophagus

瞄准：C 反应的蛋白质(CRP ) 是尖锐阶段的反应物和瘤的恶意的潜力的已知的指示物。这研究的目的是作为起作用的仙子的一个参数调查外科手术前的 CRP 的意义在有有鳞的房间癌和食道的腺癌的病人的路线和长期的预后。方法：浆液 CRP 在从 1989 年 12 月为癌症经历 oesophagectomy 到 2004 年 3 月的 371 个病人中的 291 个外科手术前地被决定。中部的耐心的年龄是 59 (28-79 ) 年， 82.5% 病人是男性。有鳞的房间癌在 151 被诊断(51.9%) 并且在 122 个病人的腺癌。Transhiatal oesophagectomy 在 151 被做(51.9%) 病人并且 134 (46.0%) 病人们经历了腹胸的过程。结果：(43.6%) 在 127，外科手术前的浆液 CRP 集中在正常以内的病人变化(【 5 mg/dL ) ，提高的 CRP 层次在 164 被测量(56.4%) 病人。瘤扩展(P 【 0.0005 ) 并且淋巴节点的数字由变形传播影响了(P = 0.015 ) 显著地与提高的 CRP 层次在这个组被增加。在起作用的仙子之中参数两输血的数字(P = 0.006 ) 并且一般复杂并发症率(P = 0.002 ) 在有提高的外科手术前的 CRP 层次的病人是更高的。13.6 的长期的幸存率(0-109.8 ) 瞬间在有与 18.9 相比的提高的 CRP 层次的组是更差的(0-155.4 ) 在有正常 CRP 的组的瞬间铺平(木头等级测试：P = 0.107 ) 。有向后的变量选择的 Multivariate 分析与食道的癌在病人作为长期的预后的一个独立预示的因素识别了外科手术前的 CRP，与 1.182 的危险比率(95% 信心间隔：1.030-1.356 ) 。结论：外科手术前的浆液 CRP 水平是在有有鳞的房间癌和食道的腺癌的病人的一个容易坚定的独立预示的标记。

Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients

AIM:To investigate the efficacy and safety of capecitabine plus irinotecan±bevacizumab in advanced or metastatic colorectal cancer patients. METHODS:Forty six patients with previously untreated,locally-advanced or metastatic colorectal cancer(mCRC) were recruited between 2001-2006 in a prospective open-label phaseⅡtrial,in German community-based outpatient clinics.Patients received a standard capecitabine plus irinotecan(CAPIRI) or CAPIRI plus bevacizumab(CAPIRI-BEV) regimen every 3 wk. Dose reductions were mandatory from the first cycle in cases of>grade 2 toxicity.The treatment choice of bevacizumab was at the discretion of the physician.Theprimary endpoints were response and toxicity and secondary endpoints included progression-free survival and overall survival. RESULTS:In the CAPIRI group vs the CAPRI-Bev group there were more female than male patients(47% vs 24%) ,and more patients had colon as the primary tumor site(58.8%vs 48.2%) with fewer patients having sigmoid colon as primary tumor site(5.9%vs 20.7%) .Grade 3/4 toxicity was higher with CAPIRI than CAPIRI-Bev:82%vs 58.6%.Partial response rates were 29.4%and 34.5%,and tumor control rates were 70.6%and 75.9%,respectively.No complete responses were observed.The median progression-free survival was 11.4 mo and 12.8 mo for CAPIRI and CAPIRI-Bev,respectively.The median overall survival for CAPIRI was 15 mo(458 d) and for CAPIRI-Bev 24 mo(733 d) .These differences were not statistically different.In the CAPIRI-Bev,group,two patients underwent a full secondary tumor resection after treatment,whereas in the CAPIRI group no cases underwent this procedure. CONCLUSION:Both regimens were well tolerated and offered effective tumor growth control in this outpatient setting.Severe gastrointestinal toxicities and thromboembolic events were rare and if observed were never fatal.

TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies

AIM:To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors,in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand(TRAIL),on overcoming TRAIL resistance in hepatocellular carcinoma(HCC)and to study the efficacy of agonistic TRAIL antibodies,as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS:Surface expression of TRAIL receptors (TRAIL-R1-4)and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting,respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNAs.HCC cellswere treated with kinase inhibitors and chemotherapeutic drugs.Apoptosis induction and cell viability were analyzed via flow cytometry and 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. RESULTS:TRAIL-R1 and-R2 were profoundly expressed on the HCC cell lines Huh7 and Hep-G2. However,treatment of Huh7 and Hep-G2 with TRAIL and agonistic antibodies only induced minor apoptosis rates.Apoptosis resistance towards TRAIL could be considerably reduced by adding the chemotherapeutic drugs 5-fluorouracil and doxorubicin as well as the kinase inhibitors LY294002[inhibition of phosphoinositol- 3-kinase(PI3K)],AG1478(epidermal growth factor receptor kinase),PD98059(MEK1),rapamycin(mam- malian target of rapamycin)and the multi-kinase inhibitor Sorafenib.Furthermore,the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL play a major role in TRAIL resistance:knock-down by RNA interference increased TRAIL-induced apoptosis of HCC cells.Additionally, knock-down of MCL-1 and BCL-xL led to a significant sensitization of HCC cells towards inhibition of both c-Jun N-terminal kinase and PI3K.CONCLUSION:Our data identify the blockage of survival kinases,combination with chemotherapeutic drugs and targeting of antiapoptotic BCL-2 proteins as promising ways to overcome TRAIL resistance in HCC.

MRI versus 64-row MDCT for diagnosis of hepatocellular carcinoma

AIM:To compare the diagnostic capability of multidetector computed tomography(MDCT) and magnetic resonance imaging(MRI) for the detection of hepatocellular carcinoma(HCC) tumour nodules and their effect on patient management.METHODS:A total of 28 patients(25 male,3 female,mean age 67±10.8 years) with biopsy-proven HCC were investigated with 64-row MDCT(slice 3 mm native,arterial and portal-venous phase,120 mL Iomeprol,4 mL/s,delay by bolus trigger) and MRI(T1fs fl2d TE/ TR 2.72/129 ms,T2tse TE/TR 102/4000 ms,5-phase dynamic contrast-enhanced T1fs fl3d TE/TR 1.56/4.6,Gadolinium-DTPA,slice 4 mm).Consensus reading of both modalities was used as reference.Tumour nodules were analyzed with respect to number,size,and location.RESULTS:In total,162 tumour nodules were detected by consensus reading.MRI detected signifi cantly more tumour nodules(159 vs 123,P<0.001) compared to MDCT,with the best sensitivity for early arterial phase MRI.False-negative CT findings included nodules ≤5 mm(n=5),≤10 mm(n=17),≤15 mm(n=12),≤20 mm(n=4),and 1 nodule >20 mm.MRI missed 2 nodules ≤10 mm and 1 nodule ≤15 mm.On MRI,nodule diameters were greater than on CT(29.2±25.1 mm,range 5-140 mm vs 24.1±22.7 mm,range 4-129 mm,P<0.005).In 2 patients,MDCT showed only unilobar tumour spread,whereas MRI revealed additional nodules in the contralateral lobe.Detection of these nodules could have changed the therapeutic strategy.CONCLUSION:Contrast-enhanced MRI is superior to 64-row MDCT for the detection of HCC nodules.Patients should be allocated to interventional or operative treatment according to a dedicated MRI-protocol.

Spreading depression and focal venous cerebral ischemia enhance cortical neurogenesis

Endogenous neurogenesis can arise from a variety of physiological stimuli including exercise, learning, or ＂enriched environment＂ as well as pathological conditions such as ischemia, epilepsy or cortical spreading depression. Whether all these conditions use a common trigger to set off endogenous neurogenesis is yet unclear. We hypothesized that cortical spreading depression（CSD） induces neurogenesis in the cerebral cortex and dentate gyrus after cerebral venous ischemia. Forty-two Wistar rats alternatively underwent sham operation（Sham）, induction of ten CSDs or venous ischemia provoked via occlusion of two adjacent superficial cortical vein followed by ten induced CSDs（CSD ＋ 2-VO）. As an additional control, 15 na？ve rats received no intervention except 5-bromo-2′-deoxyuridine（Brd U） treatment for 7 days. Sagittal brain slices（40 μm thick） were co-stained for Brd U and doublecortin（DCX; new immature neuronal cells） on day 9 or Neu N（new mature neuronal cells） on day 28. On day 9 after sham operation, cell proliferation and neurogenesis occurred in the cortex in rats. The sole induction of CSD had no effect. But on days 9 and 28, more proliferating cells and newly formed neurons in the ipsilateral cortex were observed in rats subjected to CSD ＋ 2VO than in rats subjected to sham operation. On days 9 and 28, cell proliferation and neurogenesis in the ipsilateral dentate gyrus was increased in sham-operated rats than in na？ve rats. Our data supports the hypothesis that induced cortical neurogenesis after CSD ＋ 2-VO is a direct effect of ischemia, rather than of CSD alone.

CYLD deletion triggers nuclear factor-κB-signaling and increases cell death resistance in murine hepatocytes

AIM:To analyze the role of CYLD for receptor-mediated cell death of murine hepatocytes in acute liver injury models.METHODS:Hepatocyte cell death in CYLD knockout mice(CYLD-/-)was analyzed by application of liver injury models for CD95-(Jo2)and tumor necrosis factor(TNF)-α-[D-Gal N/lipopolysaccharide(LPS)]induced apoptosis.Liver injury was assessed by measurement of serum transaminases and histological analysis.Apoptosis induction was quantified by cleaved PARP staining and Western blotting of activated caspases.Nuclear factor(NF)-κB,ERK,Akt and jun amino-terminal kinases signaling were assessed.Primary Hepatocytes were isolated by two step-collagenase perfusion and treated with recombinant TNF-αand with the CD95-ligand Jo2.Cell viability was analyzed by MTT-assay.RESULTS:Livers of CYLD-/-mice showed increased anti-apoptotic NF-κB signaling.In both applied liver injury models CYLD-/-mice showed a significantly reduced apoptosis sensitivity.After D-Gal N/LPS treatment CYLD-/-mice exhibited significantly lower levels of alanine aminotransferase(ALT)(295 U/L vs 859 U/L,P<0.05)and aspartate aminotransferase(AST)(560 U/L vs 1025 U/L,P<0.01).After Jo injection CYLD-/-mice showed 2-fold lower ALT(50 U/L vs 110 U/L,P<0.01)and lower AST(250 U/L vs 435 U/L,P<0.01)serumlevels compared to WT mice.In addition,isolated CYLD-/-primary murine hepatocytes(PMH)were less sensitive towards death receptor-mediated apoptosis and showed increased levels of Bcl-2,XIAP,c IAP1/2,survivin and c-FLIP expression upon TNF-and CD95-receptor triggering,respectively.Inhibition of NF-κB activation by the inhibitor of NF-κB phosphorylation inhibitor BAY 11-7085 inhibited the expression of antiapoptotic proteins and re-sensitized CYLD-/-PMH towards TNF-and CD95-receptor mediated cell death.CONCLUSION:CYLD is a central regulator of apoptotic cell death in murine hepatocytes by controlling NF-κB dependent anti-apoptotic signaling.

Extrinsic and intrinsic mechanisms of axon regeneration:the need for spinal cord injury treatment strategies to address both

Spinal cord injury（SCI）causes disturbances in motor and sensory functions leading to paralysis,the severity of which depends on the spinal level of the injury.Traumatic lesions of spinal cord axon projection tracts are untreatable in human patients,although numerous research groupsworldwide are studying putative treatment strategies.

Apolipoprotein A1,the neglected relative of Apolipoprotein E and its potential role in Alzheimer’s disease

Lipoproteins are multi-molecule assemblies with the primary function of transportation and processing of lipophilic substances within aqueous bodily fluids(blood,cerebrospinal fluid).Nevertheless,they also exert other physiological functions such as immune regulation.In particular,neurons are both sensitive to uncontrolled responses of the immune system and highly dependent on a controlled and sufficient supply of lipids.For this reason,the role of certain lipoproteins and their protein-component(apolipoproteins,Apo’s)in neurological diseases is perceivable.ApoE,for example,is well-accepted as one of the major risk factors for sporadic Alzheimer’s disease with a protective allele variant(ε2)and a risk-causing allele variant(ε4).ApoA1,the major protein component of high-density lipoproteins,is responsible for transportation of excess cholesterol from peripheral tissues to the liver.The protein is synthesized in the liver and intestine but also can enter the brain via the choroid plexus and thereby might have an impact on brain lipid homeostasis.This review focuses on the role of ApoA1 in Alzheimer’s disease and discusses whether its role within this neurodegenerative disorder is specific or represents a general neuroprotective mechanism.

Animal plant warfare and secondary metabolite evolution

The enduring discussion,why plants produce secondary metabolites with pharmacologically and toxicologically active towards mammals traces back to the eminent role of medicinal plants in the millennia-old history of manhood.In recent years,the concept of an animal plant warfare emerged,which focused on the co-evolution between plants and herbivores.As a reaction to herbivory,plants developed mechanical defenses such as thorns and hard shells,which paved the way for adapted animal physiques.Plants evolved further defense systems by producing chemicals that exert toxic effects on the animals that ingest them.As a result of this selective pressure,animals developed special enzymes,e.g.cytochrome P450 monooxigenases(CYP450)that metabolize xenobiotic phytochemicals.As a next step in the evolutionary competition between plants and animals,plants evolved to produce non-toxic pro-drugs,which become toxic only after ingestion by animals through metabolization by enzymes such as CYP450.Because these sequestered evolutionary developments call to mind an arms race,the term animal plant warfare has been coined.The evolutionary competition between plants and animals may help to better understand the modes of action of medicinal plants and to foster the efficient and safe use of phytotherapy nowadays.

Ectomycorrhizal diversity at five different tree species in forests of the Taunus Mountains in Central Germany

Ectomycorrhizal fungi were investigated on five different forest tree species growing in pure stands on the south slope of the Taunus Mountains, which are situated at the northern end of the Rhine rift valley in Central Germany. Mycorrhizal fungi accompanying the genus Xerocomus were identified and their frequencies counted. Using ITS markers, 22 different fungal species were identified down to species level and 6 down to genus level. On European beech (Fagus sylvatica) 16 fungal species and 4 genera were identified and on Sessile oak (Quercus petraea) 16 ectomycorrhizal species and 2 genera were determined. On both deciduous trees we observed exclusively: Cortinarius subsertipes, Genea hispidula, Lactarius quietus, Tylopilus felleus and a Melanogaster genus. On Norway spruce (Picea abies) we identified 13 different mycorrhizal species and 3 different genera, on Silver fir (Abies alba) 12 species and 3 genera, and in association with European larch (Larix decidua) 11 species and 3 genera. On these conifers Cortinarius anomalus, Lactarius necator and a Piloderma genus occurred exclusively. Comparisons with published data of ectomycorrhizal diversity on the same five tree species, growing in different areas of Germany and Europe, led to the conclusion that there is relative site specificity for ectomycorrhizal communities. Upper soil compartments of the stands investigated in the Taunus Mountainssuffer from soil acidification (pH-H20 ~3.7 to ~4.8). However, a clear correlation between upper soil pH-values and fungal diversity was not observed. On the other hand, nitrate concentrations in upper soil compartments (~26 to ~91 kgNO3-/ha) were higher in older stands as compared to younger ones. Higher nitrate concentrations in upper soils correlated with lower numbers of mycorrhizal individuals.

Multiplex neuritis in a patient with autoimmune hepatitis:A case report

A 37-year old woman presented with a 9-year history of hepatitis of unknown origin and aminotransferases within a 3-fold upper limit of normal. Autoimmune hepatitis (AIH) was diagnosed on the basis of elevated aminotransferases, soluble liver antigen/liver pancreas (SLA/LP) autoantibodies and characteristic histology. Immunosuppressive therapy led to rapid normalization of aminotransferases. Two years later, the patient developed left sided hemisensory deficits under maintenance therapy of prednisolone and azathioprine (AZT). Later she developed right foot drop and paraesthesia in the ulnar innervation territory on both sides. Magnetic resonance imaging (MRI) and cerebral panangiography suggested cerebral vasculitis. Neurological investigation and electromyography disclosed multiplex neuritis (MN) probably due to vasculitis. Consistent with this diagnosis, autoantibodies to extractable nuclear antigens were detectable in serum. Immunosuppression was changed to oral 150 mg cyclophosphamide (CPM0) per day. Prednisolone was increased to 40 mg/d and then gradually tapered to 5 mg. Oral CPM was administered up to a total dose of 40 g and then substituted by 6 times of an intervall infusion therapy of CPM (600 mg/m2). Almost complete motoric remission was achieved after 3 mo of CPM. Sensibility remained reduced in the right peroneal innervation territory. Follow-up of cranial MRI provided stable fi ndings without any new or progressive lesions. This is the fi rst report of multiplex neuritis in a patient with autoimmune hepatitis.

Calcar-guided short-stem total hip arthroplasty: Will it be the future standard? Review and perspectives

Short stems in total hip arthroplasty(THA)are becoming increasingly popular.In Germany,already 10.4%of all primary THAs are performed using a cementless short stem.The concept of modern,calcar-guided,short stems aims for an individualized reconstruction of the hip anatomy by following the calcar of the femoral neck,a bone-and soft-tissue-sparing implantation technique,and physiological loading.The stem design uses either metaphyseal fixation alone or additional diaphyseal anchoring,depending on the stem alignment and indication.These individualized anchorage types increase the potential indications for the safe use of a short stem.The design features may account for potential advantages of current short stem implants compared with earlier shortstem designs,particularly in cases of reduced bone quality or osteonecrosis of the femoral head and femoral neck fractures.The implantation technique,however,requires distinct knowledge regarding the characteristics of varus and valgus positioning,with the potential for clinical consequences.A learning curve for surgeons new to this technique must be taken into account.Cortical contact with the distal lateral cortex appears to be crucial to provide sufficient primary stability,and the use of intraoperative imaging to identify“undersizing”is highly recommended.Current results of several national registries indicate that calcarguided short stems are among the most successful implants in terms of mid-term survivorship.However,long-term data remain scarce.This review introduces the characteristics of calcar-guided short-stem THA and summarizes the current evidence.

Image cytometric DNA analysis of mucosal biopsies in patients with primary achalasia

瞄准：为随后的快速的诊断在弛缓不能病人的粘膜活体检视决定 DNA 非整倍性。方法：从中间的活体检视第三根食管与弛缓不能在 15 个病人被获得。染色的 Immunohistochemical 为 p53 为 Ki67 和 PAb 1801 与单音的同种细胞的抗体 MIB-1 被执行，除了为发育异常的常规 histologic 考试。新鲜活体检视材料的原子核是酶的联盟者并且机械地孤立，并且 DNA 内容在福尔根的染色以后与图象血细胞计数被决定。恶意分级的 DNA 根据 Boecking 被估计决定在正常双山峰附近注意的 DNA 价值的可变性。测量的进一步的索引包括了整倍体的率，和 5c- ， 7c-exceeding 和 9c-exceeding 评价。结果：组织学的考试没表明发育异常；当时 MIB-1 (基础) 在 8/15 弛缓不能标本显示出阳性反应， p53 在所有标本是否定的。图象 cytometric DNA 分析在 4/15 (26.7%) 检测了非整倍性标本。从有象标本一样的有鳞的房间癌的 15 个病人的样品只获得了 2 对作为参考测试服务的肿瘤厘米近似。象 9 件 peritumoral 样品(9/15 ) 一样的所有癌(15/15 ) 是一整倍体。从有 peritumoral 和癌标本的弛缓不能病人的活体检视的比较统计上揭示了有效差量考虑整倍体的率(双：P 【 0.0001；四倍的：P = 0.001 ) ，根据 Boecking 恶意分级(P 【 0.0001 ) 并且 5c-(P 【 0.0001 ) ， 7c-(P 【 0.0001 ) ，并且 9c-(P = 0.0001 ) 在各自的顺序与 progredient DNA 改变超过率。结论：发现那 DNA 非整倍性被图象血细胞计数与弛缓不能在病人的食道的标本识别，它可能由于在 27% 病人作为癌前期损害介绍的特定的染色体改变，导致我们断定图象血细胞计数代表一个珍贵屏蔽工具。

Intrahepatic cholangiocarcinoma: Introducing the preoperative prediction score based on preoperative imaging

Background: Intrahepatic cholangiocarcinoma(ICC) still has a poor long-term outcome, even after complete resection. We investigated different parameters gathered in preoperative imaging and analyzed their influence on resectability, recurrence, and survival. Methods: All patients who underwent exploration due to ICC between January 2008 and June 2018 were analyzed retrospectively. Kaplan-Meier model, log-rank test and Cox regression were used. Results: Out of 184 patients, 135(73.4%) underwent curative intended resection. Median overall survival(OS) was 22.2 months with a consecutive 1-, 3-and 5-year OS of 73%, 29%, and 17%. Median recurrencefree survival(RFS) was 9.3 months with a consecutive 1-, 3-and 5-year RFS of 36%, 15%, and 11%. Site of tumor, parenchymal localization, tumor configuration/dissemination, and estimated tumor volume had significant influence on resectability. Univariate analyses showed that site of tumor, tumor configuration/dissemination, number of nodules, and estimated tumor volume had predictive values for OS and RFS. Together with tumor size the preoperative prediction(POP) score was created showing significance for OS and RFS(all P<0.001). In multivariate analysis, POP score(HR=1.779;95% CI: 1.26 8-2.4 95;P=0.001), T stage(HR=1.255;95% CI: 1.040-1.514;P=0.018) and N stage(HR=1.334;95% CI: 1.081-1.645;P=0.007) were the independent predictors for OS. For RFS, POP score(HR=1.733;95% CI: 1.30 0-2.311;P<0.0 01) and M stage(HR=3.036;95% CI: 1.376-6.697;P=0.006) were the independent predictors. Conclusions: The POP score showed to have a highly significant influence on OS and RFS. The score is easy to assess through preoperative imaging. For patients in the high risk group at least staging laparoscopy or preoperative chemotherapy should be evaluated, because they showed equal outcome compared to the irresectable group.

A crate of Pandora:do amyloids from bacteria promote Alzheimer’s disease?

Incidence for microbes as drivers of Alzheimer’s disease(AD)pathology:AD is the predominant neurodegenerative disease within the elderly.Over 50 million patients suffer from dementia currently world-wide and an estimated tripling of numbers within the next 30 years is expected.Only one to maximally five percent of all cases of AD are based on mutations in the amyloid precursor protein(APP)gene or within the presenilin genes(PS1/PS2)and therefore are called familial(FAD).The majority of cases has to be designated as sporadic,which frankly only means that the origin of these cases is still enigmatic.

Functional Neuroanatomy of Time-To-Passage Perception

The time until an approaching object passes the observer is referred to as time-to-passage (TTP). Accurate judgment of TTP is critical for visually guided navigation, such as when walking, riding a bicycle, or driving a car. Previous research has shown that observers are able to make TTP judgments in the absence of information about local retinal object expansion. In this paper we combine psychophysics and functional MRI (fMRI) to investigate the neural substrate of TTP processing. In a previous psychophysical study, we demonstrated that when local retinal expansion cues are not available, observers take advantage of multiple sources of information to judge TTP, such as optic flow and object retinal velocities, and integrate these cues through a flexible and economic strategy. To induce strategy changes, we introduced trials with motion but without coherent optic flow (0% coherence of the background), and trials with coherent, but noisy, optic flow (75% coherence of the background). In a functional magnetic resonance imaging (fMRI) study we found that coherent optic flow cues resulted in better behavioral performance as well as higher and broader cortical activations across the visual motion processing pathway. Blood oxygen-level-dependent (BOLD) signal changes showed significant involvement of optic flow processing in the precentral sulcus (PreCS), postcentral sulcus (PostCS) and middle temporal gyrus (MTG) across all conditions. Not only highly activated during motion processing, bilateral hMT areas also showed a complex pattern in TTP judgment processing, which reflected a flexible TTP response strategy.

500例CT引导下椎体成形术的技术、水泥骨外渗漏及并发症的分析

本研究的目的是分析最初500次椎体成形术的技术、水泥骨外渗漏情况以及相应的并发症。行CT引导下椎体成型术的适应证是骨质疏松所致的压缩性骨折或恶性肿瘤引起的骨质破坏。全部操作过程均由CT作完整记录，同时对水泥骨外渗漏和围介入手术期内的并发症以及随访中发生再次骨折的情况也进行分析。