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.     

From the Cover: Ancient DNA and multimethod dating confirm the late arrival of anatomically modern humans in southern China

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U–Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS ¹⁴C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS ¹⁴C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.

The fossil record suggests that Homo sapiens had evolved in Africa by 315,000 y ago (315 ka) (1), spread into West Asia before 177 ka (2), but disappeared and were seemingly replaced by Homo neanderthalensis until ca. 75 to 55 ka (3, 4). A second and final excursion from Africa by so-called anatomically modern humans (AMHs) occurred soon after and broadly coincides with the extinction of the last archaic hominins, ca. 40 to 30 ka (5, 6). This dispersal involved the ancestors of all present-day non-Africans and according to molecular data occurred ca. 65 to 45 ka (7, 8). Additional support for this “late dispersal” theory is provided by the geographical structure of contemporary DNA lineages with all non-Africans closely related to present-day and ancient eastern African populations (9, 10), as well as a clinal pattern of decreasing diversity from Africa to Eurasia, the signature of serial founder effect (10–12). Corroboration has also been provided by the estimated split time between western and eastern Eurasians of ca. 47 to 42 ka as determined by ancient DNA (aDNA) from the 46,880 to 43,210 cal y B.P. (calendar year before present, i.e., before AD1950) Ust’-Ishim femur (western Siberia, Russian Federation) and the 42,000 to 39,000 cal B.P. Tianyuan skeleton (Northeast China) (13–15). Finally, the upper age boundary for this dispersal is set by interbreeding between early AMHs and the Neanderthals estimated to have occurred ca. 65 to 47 ka and the ancestors of New Guineans with the Denisovans ca. 46 ka and again ca. 30 ka (13, 16–19).In contrast, some paleoanthropologists have suggested that AMHs settled mainland East Asia much earlier, within the period of ca. 120 to 70 ka, in accordance with the “early dispersal” theory. This model is based largely upon the dating of isolated human teeth recovered at Huanglong, Luna, and Fuyan caves and a partial mandible from Zhirendong in southern China (20–24). Yet several researchers have raised questions about these and other sites on the basis of uncertainties surrounding the identification of some of them as AMHs, relationships between human remains and dated materials, or limited information available about their depositional context and dating (25–27).Here, we describe the results of an investigation of the arrival time of AMHs in southern China at five apparent early AMH cave localities involving aDNA analyses of human teeth and the dating of flowstones, sediments, fossil remains, and charcoal. The five localities we studied are the following:

• 1)Huanglong cave, located about 25 km from the town of Yunxi, northern Hubei Province (Fig. 1). Excavations by the Hubei Provincial Institute of Cultural Relics and Archaeology during three field seasons from 2004 to 2006 provided a rich mammal record, comprising 91 taxa and representing a Middle to Late Pleistocene Ailuropoda-Stegodon fauna, stone artifacts, and seven AMH teeth dated indirectly with U–Th dating on thin flowstone formations ca. 101 to 81 ka (20).Open in a separate windowFig. 1.(A) Geographical location of Huanglong Cave (1), Luna Cave (2), Fuyan Cave (3), Yangjiapo Cave (4), and Sanyou Cave (5). (B) Human remains from three localities: Yangjiapo Cave (i), Sanyou Cave (ii), and Fuyan Cave (iii). b = buccal, d = distal, l = lingual, m = mesial, and o = occlusal).
• 2)Luna cave, situated in the karst mountains of the southeastern part of the Bubing basin, Guangxi Zhuang Autonomous Region (Fig. 1). A small sample of mammal fossils (Ailuropoda-Stegodon assemblage), stone artifacts, and two AMH teeth were recovered during excavations by the Natural History Museum of Guangxi Autonomous Region in 2004 and 2008. They have since been dated indirectly through U–Th dating of flowstone in the range ca. 127 to 70 ka (21).
• 3)Fuyan cave, located in Daoxian County, Hunan Province (Fig. 1). Excavations from 2011 to 2013 resulted in a large sample of mammal fossils (Ailuropoda-Stegodon faunal group) and 47 AMH teeth but no associated artifacts (22). They have been dated indirectly using U–Th dating of flowstone within the range ca. 120 to 80 ka (22). Two additional (in situ) AMH teeth, stratigraphically associated with the original finds, were recovered by us during field investigations at the site during early 2019.
• 4)Yangjiapo Cave is a large karstic chamber located in Jianshi County (Fig. 1). It was excavated during 2004 by the Hubei Provincial Institute of Cultural Relics and Archeology and yielded 11 AMH teeth found in association with the fragmentary bones of 80 species belonging to an Ailuropoda-Stegodon fauna, implying it should be of similar age to Huanglong, Luna, and Fuyan caves. No stone artifacts or other cultural remains were found.
• 5)Sanyou Cave is a small chamber within a limestone hill at the confluence of the Yangtze River and Xiling Gorge, close to Yichang city, Hubei Province (Fig. 1). A small excavation was undertaken in 1986 by the Yichang Museum and led to the recovery of a possible Late Pleistocene age partial AMH cranial vault (Fig. 1).

     

乙型肝炎e抗原阴性慢性乙型肝炎和肝硬化患者病毒基因型及丙氨酸氨基转移酶水平分析

目的观察乙型肝炎e抗原(HBeAg)阴性慢性乙型肝炎(CHB)及肝硬化患者的乙型肝炎病毒(HBV)基因型及丙氨酸氨基转移酶(ALT)水平。方法采用酶联免疫吸附法检测62例CHB和41例肝硬化患者HBV标志物和血清ALT水平,用聚合酶链反应法检测其HBV基因型。结果CHB患者中,21 例(33.9%)为HBeAg阴性,41例(66.1%)为HBeAg阳性;肝硬化患者中,28例(68.3%)为HBeAg阴性,13例(31.7%)为HBeAg阳性。CHB患者中,53例(85.5%)为C基因型,9例(14.5%)为B基因型; 肝硬化患者中39例(95.1%)为C基因型,2例(4.9%)为B基因型。HBeAg阴性CHB患者ALT>40 U/L 者的比例低于HBeAg阳性组(分别为47.6%和85.4%),差异有统计学意义(P<0.01)。HBeAg阴性肝硬化患者ALT>40 U/L者的比例低于HBeAg阳性组(分别为64.3%和92.3%)但差异无统计学意义。结论CHB 和肝硬化患者中,HBeAg阴性者的比例较高,此类患者的ALT水平较低,以C基因型占优势。