治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代...治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从"强烈推荐"到"可能有用"的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的"治疗参考浓度范围"和"剂量相关参考浓度范围"呈现给大家。本共识指南引入了"实验室警戒浓度"的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中展开更多
AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI a...AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS： It is an international multicenter study, and there were 12 centres and 125 patients （64 males, 61 females, aged 59 ± 11 years） involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a Iow-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS： CEUS with SonoVue increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS （55）, triple-phase spiral CT （61） and HRI with a liverspecific contrast agent （53）. Accuracy of detection of metastatic disease （i.e. at least one metastatic lesion） was significantly higher for CEUS （91.2%） than for unenhanced sonography （81.4%） and was similar to that of triple-phase spiral CT （89.2 %）. In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients （94.4%）. CONCLUSION： CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.展开更多
AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 m...AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.展开更多
AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A repor...AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS： None of the bifidobacteria tested induced activation of nuclear factor κB （NF-κB） indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- （LPS-） induced NF-κB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α （TNF-α） was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NF-κB activation was accompanied by a dose-dependent decrease of interleukin 8 （IL-8） secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 （Cox-2）, and intercellular adhesion molecule 1（ICAM-1）. CONCLUSION： Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.展开更多
AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveo...AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveolar echinococcosis (AE) drawn from the Echinococcus Databank of the University Hospital of Ulm was reviewed retrospectively. For this reason, CT datasets of combined positron emission tomography (PET)-CT examinations were evaluated. The diagnosis of AE was made in patients with unequivocal seropositivity; positive histological findings following diagnostic puncture or partial resection of the liver; and/or findings typical for AE at either ultrasonography, CT, magnetic resonance imaging or PET-CT. The CT-morphological findings were grouped into the new classification scheme.RESULTS: Within the classification a lesion was dedicated to one out of five “primary morphologies” as well as to one out of six “patterns of calcification”. “primary morphology” and “pattern of calcification” are primarily focussed on separately from each other and combined, whereas the “primary morphology” V is not further characterized by a “pattern of calcification”. Based on the five primary morphologies, further descriptive sub-criteria were appended to types I-III. An analysis of the calcification pattern in relation to the primary morphology revealed the exclusive association of the central calcification with type IV primary morphology. Similarly, certain calcification patterns exhibited a clear predominance for other primary morphologies, which underscores the delimitation of the individual primary morphological types from each other. These relationships in terms of calcification patterns extend into the primary morphological sub-criteria, demonstrating the clear subordination of those criteria.CONCLUSION: The proposed CT-morphological classification (EMUC-CT) is intended to facilitate the recognition and interpretation展开更多
AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echin...AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm.Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012.Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters(pre- and post-intervention), medication and surgical treatment(pre- and post-intervention), as well as complications associated with the intervention and patients‘ subsequent clinical courses were analyzed.In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed.RESULTS:Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention.The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years.The most common symptoms were jaundice, abdominal pains, and weight loss.Thenumber of interventions per patient ranged from one to ten.Endoscopic retrograde cholangiopancreatography(ERCP)was most frequently performed in combination with stent placement(82.9%),followed by percutaneous transhepatic cholangiodrainage(31.4%)and ERCP without stent placement(22.9%).In 14.3%of cases,magnetic resonance cholangiopancreatography was performed.A total of eight patients received a biliary stent.A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention.Complications(cholangitis,pancreatitis)oc展开更多
BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead ...BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIM To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODS Consecutively,five experienced examiners evaluated contrast-enhanced abdominal computed tomography(CT)scans for 200 patients with hepatic AE of each of four locations(n=50)in Germany,France and China.Therefore,we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center,performed because of hepatic AE from September 21,2007 to March 21,2018.AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT(EMUC-CT).Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging.Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion.Statistical analysis was performed using SAS Version 9.4(SAS Institute Inc.,Cary,NC,United States).RESULTS Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe(P=0.0091).A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size(P=0.0075).Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe(P<0.0001),and vascular/biliary involvement depended on lesion size.Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations:Vascular/biliary involvem展开更多
Lithium(Li)metal batteries(LMBs)can potentially deliver much higher energy density but remain plagued by uncontrollable Li plating with dendrite growth,unstable interfaces,and highly abundant excess Li(>50 mAh·...Lithium(Li)metal batteries(LMBs)can potentially deliver much higher energy density but remain plagued by uncontrollable Li plating with dendrite growth,unstable interfaces,and highly abundant excess Li(>50 mAh·cm^(-2)).Herein,different from the artificial layer or three-dimensional(3D)matrix host constructions,various dielectric polymers are initially well-comprehensively investigated from experimental characterizations to theoretical simulation to evaluate their functions in modulating Li ion distribution.As a proof of concept,a 3D interwoven high dielectric functional polymer(HDFP)nanofiber network with polar C-F dipole moments electrospun on copper(Cu)foil is designed,realizing uniform and controllable Li deposition capacity up to 5.0 mAh·cm^(-2),thereby enabling stable Li plating/stripping cycling over 1400 h at 1.0 mA·cm^(-2).More importantly,under the highcathode loading(~3.1 mAh·cm^(-2))and only 0.6×excess Li(N/P ratio of 1.6),the full cells retain capacity retention of 97.4%after 200 cycles at 3.36 mA·cm^(-2)and achieve high energy density(297.7 Wh·kg^(-1)at cell-level)under lean electrolyte conditions(15μL),much better than ever-reported literatures.Our work provides a new direction for designing high dielectric polymer coating toward high-retention-rate practical Li full batteries.展开更多
The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the ...The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.展开更多
Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because ...Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].展开更多
The ability to repair damaged or lost tissues varies significantly among vertebrates.The regenerative ability of the heart is clinically very relevant,because adult teleost fish and amphibians can regenerate heart tis...The ability to repair damaged or lost tissues varies significantly among vertebrates.The regenerative ability of the heart is clinically very relevant,because adult teleost fish and amphibians can regenerate heart tissue,but we mammals cannot.Interestingly,heart regeneration is possible in neonatal mice,but this ability is lost within 7 days after birth.In zebrafish and neonatal mice,lost cardiomyocytes are regenerated via proliferation of spared,differentiated cardiomyocytes.While some cardiomyocyte turnover occurs in adult mammals,the cardiomyocyte production rate is too low in response to injury to regenerate the heart.Instead,mammalian hearts respond to injury by remodeling of spared tissue,which includes cardiomyocyte hypertrophy.Wnt/β-catenin signaling plays important roles during vertebrate heart development,and it is re-activated in response to cardiac injury.In this review,we discuss the known functions of this signaling pathway in injured hearts,its involvement in cardiac fibrosis and hypertrophy,and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/β-catenin signaling.Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied.Thus,conflicting data have been published regarding a potential role of Wnt/β-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy.In addition,the Wnt inhibitory secreted Frizzled-related proteins(sFrps)appear to have Wnt-dependent and Wnt-independent roles in the injured heart.Thus,while the exact functions of Wnt/β-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart,but also in regenerating lower vertebrates,manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture.Hopefully,a detailed understanding of the in vivo role of Wnt/β-catenin signaling in injured mammalian and non-mammalian hearts will a展开更多
Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,...Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,etc.)have been developed to fabricate robust protein fibers.As the traditional spinning methods provide poor control over the as-spun fibers,microfluidics has been integrated with these techniques to allow the fabrication of biological fibers in a well-designed manner,with simplicity and cost efficiency.The mechanical behavior of the developed fibers can be precisely modulated by controlling the type iop and size of microfluidic channel,flow rate,and shear force.This technique has been successfully used to manufacture a broad range of protein fibers,and can accelerate the production and application of protein fibers in various fields.This review outlines recent progress in the design and fabrication of protein-based fibers based on microfluidics.We first briefly discuss the natural spider silk-spinning process and the microfluidics spinning process.Next,the fabrication and mechanical properties of regenerated protein fibers via microfluidics are discussed,followed by a discussion of recombinant protein fibers.Other sourced protein fibers are also reviewed in detail.Finally,a brief outlook on the development of microfluidic technology for producing protein fibers is presented.展开更多
Objective:To compare laparoscopic Anderson-Hynes pyeloplasty(LAHP)and retroperitoneal laparoscopic YV-pyeloplasty(LRYVP)in ureteropelvic junction obstruction(UPJ)in presence of a crossing vessels(CV).Methods:Our datab...Objective:To compare laparoscopic Anderson-Hynes pyeloplasty(LAHP)and retroperitoneal laparoscopic YV-pyeloplasty(LRYVP)in ureteropelvic junction obstruction(UPJ)in presence of a crossing vessels(CV).Methods:Our database showed 380 UPJO-cases,who underwent laparoscopic retroperitoneal surgery during the last 2 decades including 206 non-dismembered LRYVP,157 dismembered pyeloplasties LAHP,and 17 cases of laparoscopic ureterolysis.Among them 198 cases were suitable for a matched-pair(2:1)analysis comparing laparoscopic retroperitoneal non-dismembered LRYVP(Group 1,n Z 131)and dismembered LAHP(Group 2,n Z 67)in presence of a crossing vessel.Patients were matched according to age,gender,kidney functions,and obstruction grade.Complications were graded according to modified Clavien-classification.Results:Comparative data were similar between both groups(LRYVP vs.LAHP)including mean operating time(112 min vs.114 min),complication rates(4.2%vs.7.3%)mainly Grade 1e2 according to Clavien classification,and success rates(90%vs.89%).These results reflected in the reviewed literature indicate that LRYVP provides the advantage of minimal dissection in case of CV with similar outcome.However,redundant pelvis and anteriorly crossing vessels still require a dismembered pyeloplasty LAHP.Conclusion:LRYVP has achieved similar results compared with the previous golden standard of open surgery,especially in case of crossing vessels apart from presence of a redundant pelvis or anteriorly crossing vessel.This can be further improved when using the small access retroperitoneoscopic technique respectively mini-laparoscopy.展开更多
The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian fe...The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.展开更多
Dear Editor,Since its first description in South Africa in November 2021,the SARS-CoV-2 Omicron variant rapidly outcompeted the previously dominating Delta variant.Omicron is the fifth variant of concern(VOC).It conta...Dear Editor,Since its first description in South Africa in November 2021,the SARS-CoV-2 Omicron variant rapidly outcompeted the previously dominating Delta variant.Omicron is the fifth variant of concern(VOC).It contains an unusually high number of mutations compared to previous VOCs,especially in the viral Spike protein,and shows high transmissibility and efficient escape of neutralizing antibodies.展开更多
Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in p...Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.展开更多
文摘治疗药物监测(Therapeutic drug monitoring,TDM),如通过定量测定血清或血浆药物浓度指导用药剂量优化,已经成为对患者进行精神药物治疗的很有价值的工具。在患者用药依从性难以判断、药物耐受性不佳、治疗剂量下无效以及可能存在药代动力学药物-药物相互作用等情况下,测定药物浓度是很有用的。在精神科,有可能明显获益于TDM的主要患者群体包括儿童、孕妇、老年患者、智力障碍患者、涉及司法的患者、已知或怀疑携带药代动力学相关基因变异的患者,以及合并躯体疾病影响药代动力学的患者。然而,只有将TDM充分整合到临床治疗过程中去,才能发挥其优化药物治疗的潜在优势。为了促进TDM的合理应用,神经精神药理学与药物精神病学协会(Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie,AGNP)的TDM专家组在2004年发表了精神药物治疗药物监测指南。之后,随着知识不断更新,又有许多可能需要进行TDM的新药上市。因此,本次更新将神经精神药物的种类扩展到了128种,并将其TDM必要性划分为从"强烈推荐"到"可能有用"的四个等级。经过大量细致且全面的文献检索与分门别类的汇总整理,将基于循证医学理念的"治疗参考浓度范围"和"剂量相关参考浓度范围"呈现给大家。本共识指南引入了"实验室警戒浓度"的新概念,即实验室需要马上告知治疗医生的药物浓度上限。本共识指南还给出了诸如药物作为细胞色素P450酶的底物和抑制剂的性质,代谢物与母药浓度比值的常见范围,以及与结果解释相关的内容,还提供了何时将TDM与遗传药理学检测相结合的建议。遵循本指南,有助于改善许多患者精神药物治疗的效果,特别是那些存在药代动力学异常的患者。TDM是一门交叉学科,有时针对看起来不一致的数据,需要多学科坦诚地讨论,只有这样,患者才能从这种合作中
文摘AIM： To evaluate contrast-enhanced ultrasonography （CEUS） using SonoVue in the detection of liver metastases in patients with known extrahepatic primary tumors versus the combined gold standard comprising CT, MRI and clinical/histological data. METHODS： It is an international multicenter study, and there were 12 centres and 125 patients （64 males, 61 females, aged 59 ± 11 years） involved, with 102 patients per protocol. Primary tumors were colorectal in 35%, breast in 27%, pancreatic in 17% and others in 21%. CEUS using SonoVue was employed with a Iow-mechanical-index technique and contrast-specific software using Siemens Elegra, Philips HDI 5000 and Acuson Sequoia; continuous scanning for at least five minutes. RESULTS： CEUS with SonoVue increased significantly the number of focal liver lesions detected versus unenhanced sonography. In 31.4% of the patients, more lesions were found after contrast enhancement. The total numbers of lesions detected were comparable with CEUS （55）, triple-phase spiral CT （61） and HRI with a liverspecific contrast agent （53）. Accuracy of detection of metastatic disease （i.e. at least one metastatic lesion） was significantly higher for CEUS （91.2%） than for unenhanced sonography （81.4%） and was similar to that of triple-phase spiral CT （89.2 %）. In 53 patients whose CEUS examination was negative, a follow-up examination 3-6 months later confirmed the absence of metastatic lesions in 50 patients （94.4%）. CONCLUSION： CEUS is proved to be reliable in the detection of liver metastases in patients with known extrahepatic primary tumors and suspected liver lesions.
文摘AIM: To establish an ultrasonographic classification based on a large sample of patients with confirmed hepatic alveolar echinococcosis(AE).METHODS: Clinical data and ultrasonography(US) findings of 185 patients(100 males; 85 females; mean age at diagnosis: 51.4 ± 17.6 years; mean age at time of US examination: 58.7 ± 18.2 years) were retrospectively reviewed with respect to the US morphology of hepatic AE lesions. The sonomorphological findings were grouped according to a five-part classification scheme.RESULTS: Application of the new classification resulted in the following distribution of sonomorphological patterns among the patients examined: hailstorm(54.1%); pseudocystic(13.5%); ossification(13.0%); hemangioma-like(8.1%); and metastasis-like(6.5%). Only 4.9% of lesions could not be assigned to a sonomorphological pattern.CONCLUSION: The sonomorphological classification proposed in the present study facilitates the diagnosis,interpretation and comparison of hepatic alveolar echinococcosis in routine practice and in the context of scientific studies.
文摘AIM： Different strains of bifidobacteria were analysed for their effects on HT-29 intestinal epithelial cells （IECs） in in vitro models both of the non-inflamed and inflamed intestinal epithelium. METHODS： A reporter gene system in HT-29 cells was used to measure levels of NF-KB activation after challenge with bifidobacteria or after bacterial pre-treatment following LPS challenge. IL-8 protein and pro-inflammatory gene expression was investigated using normal HT-29 cells. RESULTS： None of the bifidobacteria tested induced activation of nuclear factor κB （NF-κB） indicating that bifidobacteria themselves do not induce inflammatory events in IECs. However, six out of eight bifidobacteria tested inhibited lipopolysaccharide- （LPS-） induced NF-κB activation in a dose- and strain-dependent manner. In contrast, NF-κB activation in response to challenge with tumor necrosis factor-α （TNF-α） was affected by none of the tested bifidobacteria, indicating that the inhibitory effect of bifidobacteria is specific for LPS-induced inflammation in IECs. As shown with two of the six inhibitionpositive bifidobacteria, LPS-induced inhibition of NF-κB activation was accompanied by a dose-dependent decrease of interleukin 8 （IL-8） secretion and by lower mRNA levels for IL-8, TNF-α, cyclooxygenase 2 （Cox-2）, and intercellular adhesion molecule 1（ICAM-1）. CONCLUSION： Some strains of bifidobacteria are effective in inhibiting LPS-induced inflammation and thus might be appropriate candidates for probiotic intervention in chronic intestinal inflammation.
文摘AIM: To establish a computed tomography (CT)-morphological classification for hepatic alveolar echinococcosis was the aim of the study.METHODS: The CT morphology of hepatic lesions in 228 patients with confirmed alveolar echinococcosis (AE) drawn from the Echinococcus Databank of the University Hospital of Ulm was reviewed retrospectively. For this reason, CT datasets of combined positron emission tomography (PET)-CT examinations were evaluated. The diagnosis of AE was made in patients with unequivocal seropositivity; positive histological findings following diagnostic puncture or partial resection of the liver; and/or findings typical for AE at either ultrasonography, CT, magnetic resonance imaging or PET-CT. The CT-morphological findings were grouped into the new classification scheme.RESULTS: Within the classification a lesion was dedicated to one out of five “primary morphologies” as well as to one out of six “patterns of calcification”. “primary morphology” and “pattern of calcification” are primarily focussed on separately from each other and combined, whereas the “primary morphology” V is not further characterized by a “pattern of calcification”. Based on the five primary morphologies, further descriptive sub-criteria were appended to types I-III. An analysis of the calcification pattern in relation to the primary morphology revealed the exclusive association of the central calcification with type IV primary morphology. Similarly, certain calcification patterns exhibited a clear predominance for other primary morphologies, which underscores the delimitation of the individual primary morphological types from each other. These relationships in terms of calcification patterns extend into the primary morphological sub-criteria, demonstrating the clear subordination of those criteria.CONCLUSION: The proposed CT-morphological classification (EMUC-CT) is intended to facilitate the recognition and interpretation
文摘AIM:To determine the long-term hepatobiliary complications of alveolar echinococcosis(AE) and treatment options using interventional methods.METHODS:Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm.Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012.Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters(pre- and post-intervention), medication and surgical treatment(pre- and post-intervention), as well as complications associated with the intervention and patients‘ subsequent clinical courses were analyzed.In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed.RESULTS:Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention.The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years.The most common symptoms were jaundice, abdominal pains, and weight loss.Thenumber of interventions per patient ranged from one to ten.Endoscopic retrograde cholangiopancreatography(ERCP)was most frequently performed in combination with stent placement(82.9%),followed by percutaneous transhepatic cholangiodrainage(31.4%)and ERCP without stent placement(22.9%).In 14.3%of cases,magnetic resonance cholangiopancreatography was performed.A total of eight patients received a biliary stent.A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention.Complications(cholangitis,pancreatitis)oc
基金Supported by a German Research Foundation funded project called“Establishment of a national database for alveolar echinococcosis”,No.KA 4356/3-1“Implementation of interfaces for the standardization of nationaldatabase systems for alveolar echinococcosis and its transformation processes”,No.KR 5204/1-2+1 种基金Multiple imaging study of the Hepatic Alveolar Echinococcosis after albendazole treatment,the Qinghai Science and Technology Department,No.2017-SF-158and the Müller Holding Ltd.and Co.KG Ulm.
文摘BACKGROUND The main endemic areas of alveolar echinococcosis(AE)are in Central Europe and Western China.Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE.AIM To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim.METHODS Consecutively,five experienced examiners evaluated contrast-enhanced abdominal computed tomography(CT)scans for 200 patients with hepatic AE of each of four locations(n=50)in Germany,France and China.Therefore,we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center,performed because of hepatic AE from September 21,2007 to March 21,2018.AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT(EMUC-CT).Distant extrahepatic manifestations were documented either by whole body positron emission tomography–CT or with the addition of thoracic CT and cranial magnetic resonance imaging.Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion.Statistical analysis was performed using SAS Version 9.4(SAS Institute Inc.,Cary,NC,United States).RESULTS Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe(P=0.0091).A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size(P=0.0075).Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe(P<0.0001),and vascular/biliary involvement depended on lesion size.Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations:Vascular/biliary involvem
基金This work was financial supported by the National Natural Science Foundation of China(Nos.51877132,52003153,and 22005186)the Program of Shanghai Academic Research Leader(No.21XD1401600).
文摘Lithium(Li)metal batteries(LMBs)can potentially deliver much higher energy density but remain plagued by uncontrollable Li plating with dendrite growth,unstable interfaces,and highly abundant excess Li(>50 mAh·cm^(-2)).Herein,different from the artificial layer or three-dimensional(3D)matrix host constructions,various dielectric polymers are initially well-comprehensively investigated from experimental characterizations to theoretical simulation to evaluate their functions in modulating Li ion distribution.As a proof of concept,a 3D interwoven high dielectric functional polymer(HDFP)nanofiber network with polar C-F dipole moments electrospun on copper(Cu)foil is designed,realizing uniform and controllable Li deposition capacity up to 5.0 mAh·cm^(-2),thereby enabling stable Li plating/stripping cycling over 1400 h at 1.0 mA·cm^(-2).More importantly,under the highcathode loading(~3.1 mAh·cm^(-2))and only 0.6×excess Li(N/P ratio of 1.6),the full cells retain capacity retention of 97.4%after 200 cycles at 3.36 mA·cm^(-2)and achieve high energy density(297.7 Wh·kg^(-1)at cell-level)under lean electrolyte conditions(15μL),much better than ever-reported literatures.Our work provides a new direction for designing high dielectric polymer coating toward high-retention-rate practical Li full batteries.
基金The Deutsche Forschungsgemeinschaft, No. Ni575/4-1
文摘The gastrointestinal innate and adaptive immune system continuously faces the challenge of potent stimuli from the commensal microflora and food constituents. These local immune responses require a tight control, the outcome of which is in most cases the induction of tolerance. Local T cell immunity is an important compartment of the specif ic intestinal immune system. T cell reactivity is programmed during the initial stage of its activation by professional presenting cells. Mucosal dendritic cells (DCs) are assumed to play key roles in regulating immune responses in the antigen-rich gastrointestinal environment. Mucosal DCs are a heterogeneous population that can either initiate (innate and adaptive) immune responses, or control intestinal inflammation and maintain tolerance. Defects in this regulation are supposed to lead to the two major forms of inflammatory bowel disease (IBD), Crohn's disease (CD) and ulcerative colitis (UC). This review will discuss the emerging role of mucosal DCs in regulating intestinal inflammation and immune responses.
基金the National Natural Science Foundation of China(81520108016,81661148045,and 31471084 to Yu-Feng Zang81671774 and 81630031 to Chao-Gan Yan+11 种基金81571228 to Tao Wu61571047 to Xia Wu81701664 to Jian Wang,81471654 to Biao Huang81701671 to Wei-Guo Liu82001898 to Xi-Ze Jia81771820,81371519 and 81571654 to Wei Luo)Henry G Leong Endowed Professorship in Neurology to Shu-Leong Ho and Shirley YY Pang,BRC for Mental Health at South London and Maudsley NHS Foundation Trust and by the Sackler Institute to Grainne McAlonan,NIH(2R01AG006457 to Fay B.Horak1RC4NS073008-01 and P50NS062684 to Tara Madhyastha)NINDS Intramural Research Program to Mark HallettStart-up Funds for Leading Talents at Beijing Normal UniversityNational Basic Science Data Center‘‘Chinese Data-sharing Warehouse for In-vivo Imaging Brain”(NBSDC-DB-15)to Xi-Nian ZuoGrant NU20-04-00294 of the Agency for Health Research,Czech Republic to Lenka Krajcovicova and Irena Rektorova。
文摘Thousands of resting state functional magnetic resonance imaging(RS-f MRI)articles have been published on brain disorders.For precise localization of abnormal brain activity,a voxel-level comparison is needed.Because of the large number of voxels in the brain,multiple comparison correction(MCC)must be performed to reduce false positive rates,and a smaller P value(usually including either liberal or stringent MCC)is widely recommended[1].
文摘The ability to repair damaged or lost tissues varies significantly among vertebrates.The regenerative ability of the heart is clinically very relevant,because adult teleost fish and amphibians can regenerate heart tissue,but we mammals cannot.Interestingly,heart regeneration is possible in neonatal mice,but this ability is lost within 7 days after birth.In zebrafish and neonatal mice,lost cardiomyocytes are regenerated via proliferation of spared,differentiated cardiomyocytes.While some cardiomyocyte turnover occurs in adult mammals,the cardiomyocyte production rate is too low in response to injury to regenerate the heart.Instead,mammalian hearts respond to injury by remodeling of spared tissue,which includes cardiomyocyte hypertrophy.Wnt/β-catenin signaling plays important roles during vertebrate heart development,and it is re-activated in response to cardiac injury.In this review,we discuss the known functions of this signaling pathway in injured hearts,its involvement in cardiac fibrosis and hypertrophy,and potential therapeutic approaches that might promote cardiac repair after injury by modifying Wnt/β-catenin signaling.Regulation of cardiac remodeling by this signaling pathway appears to vary depending on the injury model and the exact stages that have been studied.Thus,conflicting data have been published regarding a potential role of Wnt/β-catenin pathway in promotion of fibrosis and cardiomyocyte hypertrophy.In addition,the Wnt inhibitory secreted Frizzled-related proteins(sFrps)appear to have Wnt-dependent and Wnt-independent roles in the injured heart.Thus,while the exact functions of Wnt/β-catenin pathway activity in response to injury still need to be elucidated in the non-regenerating mammalian heart,but also in regenerating lower vertebrates,manipulation of the pathway is essential for creation of therapeutically useful cardiomyocytes from stem cells in culture.Hopefully,a detailed understanding of the in vivo role of Wnt/β-catenin signaling in injured mammalian and non-mammalian hearts will a
文摘Lightweight and mechanically strong natural silk fibers have been extensively investigated over the past decades.Inspired by this research,many artificial spinning techniques(wet spinning,dry spinning,electrospinning,etc.)have been developed to fabricate robust protein fibers.As the traditional spinning methods provide poor control over the as-spun fibers,microfluidics has been integrated with these techniques to allow the fabrication of biological fibers in a well-designed manner,with simplicity and cost efficiency.The mechanical behavior of the developed fibers can be precisely modulated by controlling the type iop and size of microfluidic channel,flow rate,and shear force.This technique has been successfully used to manufacture a broad range of protein fibers,and can accelerate the production and application of protein fibers in various fields.This review outlines recent progress in the design and fabrication of protein-based fibers based on microfluidics.We first briefly discuss the natural spider silk-spinning process and the microfluidics spinning process.Next,the fabrication and mechanical properties of regenerated protein fibers via microfluidics are discussed,followed by a discussion of recombinant protein fibers.Other sourced protein fibers are also reviewed in detail.Finally,a brief outlook on the development of microfluidic technology for producing protein fibers is presented.
文摘Objective:To compare laparoscopic Anderson-Hynes pyeloplasty(LAHP)and retroperitoneal laparoscopic YV-pyeloplasty(LRYVP)in ureteropelvic junction obstruction(UPJ)in presence of a crossing vessels(CV).Methods:Our database showed 380 UPJO-cases,who underwent laparoscopic retroperitoneal surgery during the last 2 decades including 206 non-dismembered LRYVP,157 dismembered pyeloplasties LAHP,and 17 cases of laparoscopic ureterolysis.Among them 198 cases were suitable for a matched-pair(2:1)analysis comparing laparoscopic retroperitoneal non-dismembered LRYVP(Group 1,n Z 131)and dismembered LAHP(Group 2,n Z 67)in presence of a crossing vessel.Patients were matched according to age,gender,kidney functions,and obstruction grade.Complications were graded according to modified Clavien-classification.Results:Comparative data were similar between both groups(LRYVP vs.LAHP)including mean operating time(112 min vs.114 min),complication rates(4.2%vs.7.3%)mainly Grade 1e2 according to Clavien classification,and success rates(90%vs.89%).These results reflected in the reviewed literature indicate that LRYVP provides the advantage of minimal dissection in case of CV with similar outcome.However,redundant pelvis and anteriorly crossing vessels still require a dismembered pyeloplasty LAHP.Conclusion:LRYVP has achieved similar results compared with the previous golden standard of open surgery,especially in case of crossing vessels apart from presence of a redundant pelvis or anteriorly crossing vessel.This can be further improved when using the small access retroperitoneoscopic technique respectively mini-laparoscopy.
文摘The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.
基金supported by the DFG(CRCs 1279 and 1506)the EU commission(Fight-nCoV)the MWK and the BMBF(Restrict-SARS-CoV-2,IMMUNOMOD).
文摘Dear Editor,Since its first description in South Africa in November 2021,the SARS-CoV-2 Omicron variant rapidly outcompeted the previously dominating Delta variant.Omicron is the fifth variant of concern(VOC).It contains an unusually high number of mutations compared to previous VOCs,especially in the viral Spike protein,and shows high transmissibility and efficient escape of neutralizing antibodies.
基金supported by grants from the“PAKT für Forschung und Innovation2010(Leibniz Age Net:signaling pathways in age-related diseases)”German Research Foundation(DFG)Tu220/14-1,DFG(No.Ci 216/2-1)+1 种基金DFG in the framework of Collaborative Research Center CRC1149“Danger Response,Disturbance Factors and Regenerative Potential after Trauma”(No.251293561—CRC 1149,INST 40/492-1 and INST 40/492-2)Open Access funding enabled and organized by Projekt DEAL。
文摘Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis,a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5(Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by si RNA, genetic deletion using the Cre-lox P system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.
