Subcutaneous granuloma caused by Kodamaea ohmeri in an immunocompromised patient in China

We present a case of subcutaneous granuloma caused by Kodamaea ohmeri and describe the histopathological characteristics and skin lesions caused by this pathogen. A 55-year-old woman, with a history of rheumatoid arthritis, presented with red, painless plaque on her forehead, persistent for 3 months; based on the histopathological and mycological findings and gene sequencing, the patient was diagnosed with subcutaneous granuloma caused by K. ohmeri. This report highlights that early identification and diagnosis and optimal regimens are vital in the management of this intractable infection.     

急性单发腔隙性脑梗死患者BG/CSO-VRS扩大严重程度的危险因素分析

目的 探讨急性单发腔隙性脑梗死患者基底节(basal ganglia,BG)/半卵圆中心(central semioval,CSO)-血管周围间隙(Virchow-Robin Spaces,VRS)扩大严重程度的危险因素。方法 回顾性分析本院2018年1月-2019年3月收治急性单发腔隙性脑梗死患者共476例的临床资料,其中基底节(BG)梗死262例,半卵圆中心(CSO)梗死214例,根据影像学手段评估BG/CSO-VRS扩大严重程度; 采用χ²检验和Logistic回归模型分析确定BG/CSO-VRS扩大严重程度的相关危险因素。结果 基底节和半卵圆中心梗死VRS评分比较无显著差异(P>0.05); BG-VRS轻度扩大和重度扩大患者性别、高血压病比例、收缩压及BMI水平比较有明显差异(P<0.05); CSO-VRS轻度和重度扩大患者高血压病、糖尿病比例及BMI水平比较有明显差异(P<0.05); 采用多因素Logistic回归模型分析显示,高血压病和BMI均是BG-VRS扩大严重程度的独立影响因素(P<0.05),而BMI也是CSO-VRS扩大严重程度的独立影响因素(P<0.05)。结论 高血压病和BMI与急性单发腔隙性脑梗死患者VRS扩大密切相关,其中合并高血压病和BMI降低是导致BG-VRS扩大的独立危险因素,而BMI降低也是CSO-VRS扩大的独立危险因素     

The role of replay and theta sequences in mediating hippocampal‐prefrontal interactions for memory and cognition

Sequential activity is seen in the hippocampus during multiple network patterns, prominently as replay activity during both awake and sleep sharp‐wave ripples (SWRs), and as theta sequences during active exploration. Although various mnemonic and cognitive functions have been ascribed to these hippocampal sequences, evidence for these proposed functions remains primarily phenomenological. Here, we briefly review current knowledge about replay events and theta sequences in spatial memory tasks. We reason that in order to gain a mechanistic and causal understanding of how these patterns influence memory and cognitive processing, it is important to consider how these sequences influence activity in other regions, and in particular, the prefrontal cortex, which is crucial for memory‐guided behavior. For spatial memory tasks, we posit that hippocampal‐prefrontal interactions mediated by replay and theta sequences play complementary and overlapping roles at different stages in learning, supporting memory encoding and retrieval, deliberative decision making, planning, and guiding future actions. This framework offers testable predictions for future physiology and closed‐loop feedback inactivation experiments for specifically targeting hippocampal sequences as well as coordinated prefrontal activity in different network states, with the potential to reveal their causal roles in memory‐guided behavior.     

Design,synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7 , 14 , and 15 were obtained with EC₅₀ values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7 , 14 , and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.     

Evaluation of the sensitivity of Microhyla fissipes tadpoles to aqueous cadmium

Cadmium (Cd) exposure is harmful to amphibians in natural environments and the Cd concentration is a key parameter in water monitoring. Cd pollution has been a severe issue in the Yangtze River and its southern reaches in recent years. Acute toxicity assays were employed to determine the tolerance limits of Cd for Microhyla fissipes tadpoles and five different concentrations of Cd (0, 50, 100, 200 and 300 μg/L) were involved to detect its chronic effects on metamorphosis, growth, locomotion, genotoxicity and enzymatic activities of M. fissipes tadpoles. The results showed that the 24-h and 48-h LC₅₀ values of Cd on M. fissipes tadpoles were 2591.3 μg/L and 1567.9 μg/L, respectively, and the presumable non-lethal concentration obtained was 172.2 μg/L. During the 70-day chronic toxicity assays, Cd showed negative impacts on survival, growth, metamorphosis and the frequency of erythrocytes nuclear abnormality of M. fissipes tadpoles. However, the Cd exposure caused the increased body size and condition of tadpoles at complete metamorphosis (GS46). The tadpoles exposed to 200 μg/L of Cd exhibited degraded locomotor performance at GS46. Weight increments of tadpoles were inhibited at Day 14 and massive deaths were observed over the next 14 days. The enzymatic activities of tadpoles experienced a shock response stage (GS30-GS35) and a complete recovery stage (GS36-GS41) in all treatments. However, the enzymatic activities (except alkaline phosphatase) of tadpoles at GS46 increased after Cd exposure, especially at high concentrations. In summary, Cd is a threat to M. fissipes tadpoles as that causes reduced fitness.

     

基于共词分析法分析新生儿重症监护领域超药品说明书用药现状

目的探讨采用共词分析法对基于文献报道的国内外新生儿重症监护领域超药品说明书用药(OLDU)现状，旨在为该领域OLDU研究提供方向。 方法本研究以"新生儿重症监护""超说明书用药"为中文关键词，在中国知网(CNKI)数据库、万方数据库中进行文献检索；同时，以"neonatal intensive care""off-label drug"为英文关键词，在MEDLINE数据库中进行检索。设定文献检索时间为各个数据库建库至2018年6月31日。选择由此获取的符合本研究纳入标准与排除标准的42篇新生儿童症监护领域OLDU相关文献为研究对象。其中，中文文献为3篇，英文文献为39篇。采用Microsoft Office Excel 2016软件对39篇英文文献关键词进行录入、整理。由于该领域中文文献数量太少(3篇)，无法建立中文文献的关键词共现矩阵，故仅对英文文献关键词进行提取。对纳入研究的39篇英文文献提取关键词后，继续采用该软件建立关键词共现矩阵，使用Ucinet 6.2绘制关键词共现网络知识图谱，并进行新生儿重症监护领域OLDU共词分析。 结果自纳入本研究的新生儿重症监护领域OLDU的39篇英文文献中，提取关键词共计18个，最早的文献发表于1999年，并且进行这方面研究文献的数量呈逐年升高趋势。新生儿重症监护领域OLDU英文文献关键词共现网络知识图谱显示，位于图谱中心的是"neonate(新生儿)""off-label drug(超说明书药物)"和"preterm(早产儿)"；其次"audit(审查)""antibiotic(抗菌药物)""inhaled nitric oxide(吸入一氧化氮)"也是较为热门关键词。此外，关键词"pharmacokinetics(药物代谢动力学)"的位置虽然偏离核心关键词，但是与关键词"neonate(新生儿)"的联系较为紧密(连线较粗)。 结论新生儿重症监护领域OLDU相关问题并不少见，国外对该领域的关注时间较长、研究范围覆盖面较广。我国对该领域的研究处于起步阶段，目前需要加强对新生儿重症监护领域OLDU的重视和关注，并开展相关临床试验，以保障新生儿患者用药安全。     

不良孕产史夫妇染色体核型的大样本分析

目的探讨不良孕产史夫妇染色体异常核型检出率及其分布，以及染色体异常核型与不良孕产史的关系，为优生优育及遗传咨询提供理论依据。 方法选取2016年1月1日至2017年12月31日，于济南艾迪康医学检验中心进行染色体核型检测的10 330对(20 660例)不良孕产史育龄夫妇为研究对象。采集每例受试者肘静脉血3 mL，肝素钠抗凝，取0.3 mL进行血细胞培养、标本制备，采用常规G显带技术进行染色体核型分析。对于染色体异常核型检出率、不同类型染色体异常核型占染色体异常核型总例数的比例等计数资料，采用率(%)表示。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。 结果①本组10 330对(20 660例)不良孕产史育龄夫妇中，共计检出染色体异常核型为1 119例(不含染色体多态性)，染色体异常核型检出率为5.42%(1 119/20 660)。其中，常染色体异常者为658例，占染色体异常核型的58.80%(658/1 119)，包括354例染色体平衡易位、205例染色体倒位、83例染色体罗伯逊易位、11例染色体插入、5例染色体重复，分别占染色体异常核型的31.64%、18.32%、7.41%、0.98%、0.45%。染色体倒位者中，以9号染色体倒位居多，偶见于1、4、7、11、12号染色体，并且多合并自然流产。性染色体异常者为440例，占染色体异常核型的39.32%(440/1 119)，包括365例性染色体数目异常(占染色体异常核型的32.62%)。其中，男性多表现为无精子症，以47，XXY染色体异常核型居多(144例)，女性多表现为原发性不孕，以45，X染色体异常核型居多(103例); 61例为性染色体结构异常、14例为性别反转，分别占染色体异常核型的5.45%、1.25%。其他罕见染色体异常核型者为21例，占染色体异常核型的1.88%(21/1 119)，如环状染色体、mar染色体等。②本组10 330对(20 660例)不良孕产史育龄夫妇中，11例为常染色体插入，5例为常染色体重复，54例为性染色体缺失，其主要临床表现为原发性不孕不育、胚胎停止发育、无精子症或重度少精子症。 结论染色体异常核型是导致育龄期夫妇不良孕产史的重要原因之一。对于不良孕产史夫妇，建议进行染色体核型分析和遗传咨询。临床为这类患者进行优生优育指导，可提高出生人口质量。     

Heal or no heel: Outcomes of ischaemic heel ulcers following lower limb revascularization from a multi‐ethnic Asian Cohort in Singapore

Ischaemic diabetic heel ulcers are difficult to treat and prognosis is often guarded. The aim was to document our outcome of treating heel ulcers following revascularization in a predominantly diabetic Asian cohort presenting with chronic limb threatening ischaemia from Singapore. Retrospective cohort study (n = 66, 66 limbs) over a 5‐year period. Data were collected from hospital electronic health records. Outcomes included time to healing, amputation free survival (AFS), and mortality. Minimum follow‐up period was 6 months. Multivariate regression analysis was performed to look for factors associated with poor outcome. Mean age was 67.4 ± 8.8 years. 62/66 (93.9%) were diabetics. Mean wound size at presentation was 3.6 ± 2.3 cm. Mean Wound, Ischaemia, Foot Infection (WIFI) score was 5 ± 1.6. 12/66 (18%) patients had a patent posterior tibial artery pre‐operatively. Straight line flow was restored in only 31/66 (46.9) patients but 47/66 (71.2%) had successful limb salvage. Median time to wound healing was 90.0 (IQR 60‐180) days. A median of 1 (IQR 0‐2) wound debridement was required. Patients who underwent negative pressure dressing (23/66; 34.8%) required a median of 26 (IQR 13‐33) cycles to achieve healing. Amputation free survival (AFS) was 72% and 68% at 6‐ and 12‐months, respectively. Mortality rate was 16.7% and 19.7% at 6‐ and 12‐months, respectively. Low albumin level and initial Rutherford class were independent predictors of worse 6‐month AFS. Outcomes of heel ulcers post revascularisation may not be as poor as previously described. Persistent attention to wound care with multidisciplinary effort is needed for optimal healing.