十二指肠非壶腹部神经内分泌肿瘤内镜下切除的回顾性研究

目的 评价内镜超声检查术（EUS）判断十二指肠非壶腹部神经内分泌肿瘤大小和浸润深度的准确性，并对比内镜黏膜下剥离术（ESD）和改良ESD治疗十二指肠非壶腹部神经内分泌肿瘤的有效性和安全性。方法 以2007年1月至2018年1月于中国人民解放军总医院接受ESD（ESD组）或改良ESD（改良ESD组）治疗的22例十二指肠非壶腹部神经内分泌肿瘤患者为研究对象，回顾性纳入患者临床资料。22例患者中，13例行ESD,9例行改良ESD。对比分析ESD组和改良ESD组整块切除率、R0切除率、手术时间、手术相关并发症发生率等指标。以术后病理结果为金标准，评估术前EUS判定病变大小和浸润深度的准确率。结果 22例十二指肠非壶腹部神经内分泌肿瘤大小为（6.9±1.5）mm。与术后组织病理学结果相对照，内镜超声评估病变浸润深度的准确性为95.5%（21/22）。ESD组和改良ESD组的R0切除率分别为13/13和7/9（100.0% 比77.8%, P=1.000）。改良ESD组在手术时间上显著短于ESD组[（16.0±2.2） min 比 （29.8±4.9）min，P<0.001]。ESD组发生1例术中穿孔和1例迟发穿孔，改良ESD组发生1例迟发出血。术后22例患者均成功进行了随访，随访时间为(30.0±24.8)个月。随访期间无患者发生局部复发或者远处转移。结论 内镜超声可以准确评价十二指肠非壶腹部神经内分泌肿瘤的大小和浸润深度。对于直径≤10 mm，浸润深度局限在黏膜下层的十二指肠非壶腹部神经内分泌肿瘤，改良ESD可以获得与ESD相当的临床治疗效果。     

Umbilical cord blood cells capable of engrafting in primary, secondary, and tertiary xenogeneic hosts are preserved after ex vivo culture in a noncontact system

This report describes stroma-based and stroma-free cultures that maintain long-term engrafting hematopoietic cells for at least 14 days ex vivo. Umbilical cord blood (UCB) CD34(+) cells were cultured in transwells above AFT024 feeders with fetal-liver-tyrosine-kinase (FL) + stem cell factor (SCF) + interleukin 7 (IL-7), or FL + thrombopoietin (Tpo). CD34(+) progeny were transplanted into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice or preimmune fetal sheep. SCID repopulating cells (SRC) with multilineage differentiation potential were maintained in FL-SCF-IL-7 or FL-Tpo containing cultures for up to 28 days. Marrow from mice highly engrafted with uncultured or expanded cells induced multilineage human hematopoiesis in 50% of secondary but not tertiary recipients. Day 7 expanded cells engrafted primary, secondary, and tertiary fetal sheep. Day 14 expanded cells, although engrafting primary and to a lesser degree secondary fetal sheep, failed to engraft tertiary recipients. SRC that can be transferred to secondary recipients were maintained for at least 14 days in medium containing glycosaminoglycans and cytokines found in stromal supernatants. This is the first demonstration that ex vivo culture in stroma-noncontact and stroma-free cultures maintains "long-term" engrafting cells, defined by their capacity to engraft secondary or tertiary hosts. (Blood. 2001;97:3441-3449)     

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection

BACKGROUNDInflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors.AIMTo investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC).METHODSWe retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection.RESULTSThe optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection.CONCLUSIONThe increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.     

急性脑梗死患者血清sICAM-1变化及临床意义

为探讨是粘附分子－1（ICAM－1）与急性脑梗死（ACI）发生发展的关系，应用酶联免疫吸附试验（ELISA）以双抗夹心法检测了48例ACI患者发病后24小时内，第3天，第7天，第14天血清内可溶性ICAM－1（sICAM-1）含量的变化，同时采用葡萄糖氧化酶法和硫代巴比妥酸法分别测定了血糖和丙二醛（MDA）水平。结果显示，ACI发病后2周的血清sICAM-1含量明显高于正常对照组（P＜0．05），发病后24小时内即见血清sICAM-1水平增高，至第3天达最高水平，以后逐渐降低。血sICAM-1水平与MDA和血糖呈正相关。认为ICAM－1参与了ACI的病理损伤过程，氧化应激和高血糖可能是加重这一病理损伤过程的重要因素。     

Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia

In a phase 2 study, 62 patients with relapsed and refractory acute myeloid leukemia (AML; n = 31), myelodysplastic syndrome (MDS; n = 8), chronic myeloid leukemia in blastic phase (CMLBP; n = 11), and acute lymphocytic leukemia (ALL; n = 12) received 40 mg/m2 clofarabine intravenously over 1 hour daily for 5 days, every 3 to 6 weeks. Twenty patients (32%) achieved complete response (CR), 1 had a partial response (PR), and 9 (15%) achieved CR but without platelet recovery (CRp), for an overall response rate of 48%. In AML, responses were noted in 2 (18%) of 11 patients in first salvage with short first CR (相似文献   

Identification of the structural mutation responsible for the dibucaine-resistant (atypical) variant form of human serum cholinesterase.

A point mutation in the gene for human serum cholinesterase was identified that changes Asp-70 to Gly in the atypical form of serum cholinesterase. The mutation in nucleotide 209, which changes codon 70 from GAT to GGT, was found by sequencing a genomic clone and sequencing selected regions of DNA amplified by the polymerase chain reaction. The entire coding sequences for usual and atypical cholinesterases were compared, and no other consistent base differences were found. A polymorphic site near the C terminus of the coded region was detected, but neither allele at this locus segregated consistently with the atypical trait. The nucleotide-209 mutation was detected in all five atypical cholinesterase families examined. There was complete concordance between this mutation and serum cholinesterase phenotypes for all 14 heterozygous and 6 homozygous atypical subjects tested. The mutation causes the loss of a Sau3A1 restriction site; the resulting DNA fragment length polymorphism was verified by electrophoresis of 32P-labeled DNA restriction fragments from usual and atypical subjects. Dot-blot hybridization analysis with a 19-mer allele-specific probe to the DNA amplified by the polymerase chain reaction distinguished between the usual and atypical genotypes. We conclude that the Asp-70----Gly mutation (acidic to neutral amino acid substitution) accounts for reduced affinity of atypical cholinesterase for choline esters and that Asp-70 must be an important component of the anionic site. Heterogeneity in atypical alleles may exist, but the Asp-70 point mutation may represent an appreciable portion of the atypical gene pool.     

Arterial manifestations of Beh?et's disease. 12 cases

Out of 196 patients with Beh?et's disease, 12 (10 men and 2 women, mean age 34 +/- 7 years) had non-coronary arterial lesions. Beh?et's disease was complete in 4 patients. The arterial lesions had appeared 8.6 +/- 8 years on average (20 years at most) after the first sign of the disease. Three patients showed evidence of stenosis or occlusion involving one or several arteries. Eight patients had both stenotic and aneurysmal lesions. One patient had an arteriovenous fistula. Another developed a false aneurysm at the site of introduction of a femoral catheter. Yet another patient developed an anastomotic aneurysm one year after implantation of an abdominal aortic graft. In 2 cases histology showed fragmentation of the media associated with vasculitis of the vasa vasorum. Two patients with pulmonary aneurysm died of massive haemoptysis. In 2 patients combined corticosteroid and cyclophosphamide therapy failed to prevent the development of aneurysmal lesions. Phlebitis was associated with arterial involvement in 7 patients. Comparison between patients with or without arterial lesions showed no significant difference in time of onset of Beh?et's disease, sex, main clinical features and presence of HLA B5. Aneurysmal lesions respond poorly to medical treatment, and surgery is mandatory. Since recurrence at the site of anastomosis is possible, prolonged monitoring is required.     

BMI Trajectories as a Harbinger of Pre-Diabetes or Underdiagnosed Diabetes: an 18-Year Retrospective Cohort Study in Taiwan

Background

Although prior studies have examined BMI trajectories in Western populations, little is known regarding how BMI trajectories in Asian populations vary between adults with and without diabetes.

Objective

To examine how BMI trajectories vary between those developing and not developing diabetes over 18 years in an Asian cohort.

Design

Multilevel modeling was used to depict levels and rates of change in BMI for up to 18 years for participants with and without self-reported physician-diagnosed diabetes.

Participants

We used 14,490 data points available from repeated measurements of 3776 participants aged 50+ at baseline without diabetes from a nationally representative survey of the Taiwan Longitudinal Study on Aging (TLSA1989-2007).

Main Measures

We defined development of diabetes as participants who first reported diabetes diagnoses in 2007 but had no diabetes diagnoses at baseline. We defined the reference group as those participants who reported the absence of diabetes at baseline and during the entire follow-up period.

Key Results

When adjusted for time-varying comorbidities and behavioral factors, higher level and constant increases in BMI were present more than 6.5 years before self-reported diabetes diagnosis. The higher BMI level associating with the development of diabetes was especially evident in females. Within 6.5 years prior to self-reported diagnosis, however, a wider range of decreases in BMI occurred (β_diabetes?=?1.294, P?=?0.0064; β_{diabetes*time}?=?0.150, P?=?0.0327; β_{diabetes*time} ²?=??0.008, P?=?0.0065). The faster rate of increases in BMI followed by a greater decline was especially prominent in males and individuals with BMI ≧24.

Conclusions

An unintentional decrease in BMI in sharp contrast to the gradually rising BMI preceding that time may be an alarm for undiagnosed diabetes or a precursor to developing diabetes.

     

Uv-visible spectroscopy of bacteriorhodopsin mutants: substitution of Arg-82, Asp-85, Tyr-185, and Asp-212 results in abnormal light-dark adaptation.

The light-dark adaptation reactions of a set of bacteriorhodopsin (bR) mutants that affect function and color of the chromophore were examined by using visible absorption spectroscopy. The absorbance spectra of the mutants Arg-82 in equilibrium Ala (Gln), Asp-85 in equilibrium Ala (Asn, Glu), Tyr-185 in equilibrium Phe, and Asp-212 in equilibrium Ala (Asn, Glu) were measured at different pH values during and after illumination. None of these mutants exhibited a normal dark-light adaptation, which in wild-type bR causes a red shift of the visible absorption maximum from 558 nm (dark-adapted bR) to 568 nm (light-adapted bR). Instead a reversible light reaction occurs in the Asp-85 and Asp-212 mutants from a blue form with lambda max near 600 nm to a pink form with lambda max near 480 nm. This light-induced shift explains the appearance of a reversed light adaptation previously observed for the Asp-212 mutants. In the case of the Tyr-185 and Arg-82 mutants, light causes a purple-to-blue transformation similar to the effect of lowering the pH. However, the blue forms observed in these mutants are not identical to those formed by acid titration or deionization of wild-type bR. It is suggested that in all of these mutants, the chromophore has lost the ability to undergo the normal 13-cis, 15-syn to all-trans, 15-anti light-driven isomerization, which occurs in native bR. Instead these mutants may have as stable forms all-trans,syn and 13-cis,anti chromophores, which are not allowed in native bR, except transiently.