Dithieno[3,2-b:2′,3′-d]silole-based conjugated polymers for bioimaging in the short-wave infrared region

The short-wave infrared window (SWIR, 900–1700 nm) fluorescence imaging has been demonstrated to have excellent imaging performance in signal/noise ratio and tissue penetration compared to the conventional NIR biological window (NIR-I, 700–900 nm). Conventional organic SWIR fluorescent materials still suffer from low fluorescence quantum efficiency. In this work, a donor unit with sp³ hybrid configuration and an acceptor unit with small hindered alkyl side chains are employed to construct donor–acceptor (D–A) type conjugated polymers P1 and P2, which were substituted with one or two fluorine atoms. These structural features can alleviate the aggregation-caused quenching (ACQ) and contribute to charge transfer, resulting in a significantly improved fluorescence quantum efficiency. The SWIR fluorescent quantum efficiencies of P1 and P2 nanoparticles are 3.4% and 4.4%, respectively, which are some of the highest for organic SWIR fluorophores reported so far. Excellent imaging quality has been demonstrated with P2 nanoparticles for SWIR imaging of the vascular system of nude mice. The results indicate that our design strategy of introducing sp³ hybrid configuration and small hindered alkyl side chains to fabricate conjugated polymers is efficient in improving the fluorescent quantum efficiency as SWIR fluorescent imaging agents for potential clinical practice.

A D–A type polymer with a SWIR fluorescence quantum efficiency of 4.4% was obtained after structural optimization.     

Simultaneous determination of hydroquinone and catechol by a reduced graphene oxide–polydopamine–carboxylated multi-walled carbon nanotube nanocomposite

A reduced graphene oxide–polydopamine–carboxylated multi-walled carbon nanotube (RGO–PDA–cMWCNT) nanocomposite was fabricated via a facile, one-pot procedure and was characterized by a variety of techniques. A novel electrochemical sensor based on RGO–PDA–cMWCNT was constructed to determine hydroquinone (HQ) and catechol (CT) simultaneously. This newly prepared nanocomposite shows excellent electrocatalytic efficacy in the electrode reaction of the two isomers. Specifically, the peak-to-peak potential difference between the two dihydroxybenzenes is 115 mV for oxidation, which is obviously larger than similar electrochemical sensors. The established method displays a wide linear range from 0.5 to 5000 μM with a detection limit (S/N = 3) of 0.066 μM for HQ and 0.073 μM for CT. In addition, this electrochemical approach has been tested to measure the two dihydroxybenzenes in real samples and satisfactory results were recorded.

A novel reduced graphene oxide–polydopamine–carboxylated multi-walled carbon nanotube nanocomposite (RGO–PDA–cMWCNT) was fabricated for the sensitive and simultaneous determination of hydroquinone (HQ) and catechol (CT).     

Stress hyperglycemia is associated with in‐hospital mortality in patients with diabetes and acute ischemic stroke

Background and ObjectiveStress hyperglycemia may occur in diabetic patients with acute severe cerebrovascular disease, but the results regarding its association with stroke outcomes are conflicting. This study aimed to examine the association between stress‐induced hyperglycemia and the occurrence of in‐hospital death in patients with diabetes and acute ischemic stroke.Research Design and MethodsAll data were from the Chinese Stroke Center Alliance (CSCA) database and were collected between 2016 and 2018 from >300 centers across China. Patients’ demographics, clinical presentation, and laboratory data were extracted from the database. The primary endpoint was in‐hospital death. The ratio of fasting blood glucose (FBG) to HbA1c was calculated, that is, the stress‐induced hyperglycemia ratio (SHR), to determine stress hyperglycemia following acute ischemic stroke.ResultsA total of 168,381 patients were included. The mean age was 66.2 ± 10.7, and 77,688 (43.0%) patients were female. The patients were divided into two groups: survivors (n = 167,499) and non‐survivors (n = 882), as well as into four groups according to their SHR quartiles (n = 42,090–42,099/quartile). There were 109 (0.26%), 142 (0.34%), 196 (0.47%), and 435 (1.03%) patients who died in the Q1, Q2, Q3, and Q4 quartiles, respectively. Compared with Q1 patients, the death risk was higher in Q4 patients (odds ratio (OR) = 4.02) (adjusted OR = 1.80, 95% confidence interval [CI] = 1.10–2.92, p = 0.018 after adjustment for traditional cardiovascular risk factors). The ROC analyses showed that SHR (AUC = 0.667, 95% CI: 0.647–0.686) had a better predictive value for mortality than that of fasting blood glucose (AUC = 0.633, 95% CI: 0.613–0.652) and HbA1c (AUC = 0.523, 95% CI: 0.504–0.543).ConclusionsThe SHR may serve as an accessory parameter for the prognosis of patients with diabetes after acute ischemic stroke. Hyperglycemia in stroke patients with diabetes mellitus is associated with a higher risk of in‐hospital death.     

尿中双酚S测定的涡旋辅助液液微萃取-高效液相色谱法

目的:建立涡旋辅助液液微萃取-高效液相色谱法测定尿中双酚S的方法。方法:以乙腈为分散剂,正辛醇为萃取剂,萃取尿中双酚S。采用单因素轮换实验确定最佳萃取条件,并评估方法学性能指标。结果:尿中双酚S在0.0~160 μg/L范围线性相关系数大于0.999,检出限为0.76 μg/L,样品加标回收率为88.06%~103.8...     

多学科管理下鸟氨酸氨甲酰基转移酶缺乏症妇女连续三次妊娠分娩健康儿一例

本文报告1例鸟氨酸氨甲酰基转移酶缺乏症患者3次妊娠,最终在多学科管理下分娩一健康新生儿的诊疗经过。2013年患者首次妊娠,孕28周出现急性高氨血症收入上海交通大学医学院附属新华医院,诊断为鸟氨酸氨甲酰基转移酶缺乏症。给予低蛋白饮食及降血氨治疗,并在多学科管理下于孕32周剖宫产一男婴,但该男婴生后第3天死亡。基因分析提示患者及其新生儿鸟氨酸氨甲酰基转移酶基因均存在c.583G>A(G195R)突变。2015年患者再次自然妊娠,但产前诊断提示胎儿为男性,且鸟氨酸氨甲酰基转移酶基因存在同一位点纯合突变,于孕21周引产终止妊娠。2017年借助体外受精-胚胎移植及植入前基因诊断技术第3次妊娠,并在多学科管理下最终顺利分娩一名健康男婴。     

阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的多中心随机对照研究

【摘要】 目的 比较阿伐斯汀与阿伐斯汀联合氯雷他定治疗慢性难治性荨麻疹的疗效。方法 2017年3月至2018年12月,于4家中心采用多中心、随机对照的临床研究,联合治疗组慢性难治性荨麻疹患者口服阿伐斯汀胶囊8 mg每日3次及氯雷他定片10 mg每日1次,阿伐斯汀组口服阿伐斯汀胶囊8 mg每日3次及安慰剂10 mg每日1次,治疗4周。分别于治疗前、治疗1、2、4周随访,采集临床指标及记录不良反应事件。根据瘙痒、风团的数目、风团大小、每次发作持续时间、每周发作次数评估症状积分,使用症状积分下降指数（SSRI）评价疗效。采用重复测量的方差分析和χ2检验进行疗效和安全性评价。结果 联合治疗组53例、阿伐斯汀组59例纳入疗效分析。治疗前,两组症状积分、瘙痒视觉模拟评分差异均无统计学意义。治疗2周,联合治疗组痊愈19例、显效10例,有效率54.72%;阿伐斯汀组痊愈15例,显效6例,有效率35.59%。治疗4周,联合治疗组痊愈23例,显效9例,有效率60.38%;阿伐斯汀组痊愈20例,显效2例,有效率37.29%。治疗2、4周,联合治疗组有效率均高于阿伐斯汀组（χ2 = 4.13、5.96,均P < 0.05）。两组各随访时间点的SSRI差异、组间SSRI差异均有统计学意义（F = 8.62、4.38,均P < 0.05）。多变量方差分析,治疗2、4周时,联合治疗组SSRI（0.63 ± 0.05、0.68 ± 0.05）高于阿伐斯汀组（0.47 ± 0.05、0.51 ± 0.05）,差异均有统计学意义（均P < 0.05）。联合治疗组发生药物相关性不良反应7例,阿伐斯汀组3例,主要表现为嗜睡、胃部不适、头痛、肝功能异常。结论 阿伐斯汀治疗慢性难治性荨麻疹安全、有效;阿伐斯汀联合氯雷他定可以显著提高疗效。     

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.     

High mobility group box-1-toll-like receptor 4-phosphatidylinositol 3-kinase/protein kinase B-mediated generation of matrix metalloproteinase-9 in the dorsal root ganglion promotes chemotherapy-induced peripheral neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of chemotherapeutics. The mechanisms of CIPN remain substantially unidentified, although inflammation-induced peripheral sensitization has been indicated as an important factor. Here, we aimed to illustrate the role of the matrix metalloproteinase (MMP)-9-related signaling pathway in the process of CIPN. Oxaliplatin (L-OHP) was administered to mice to establish the CIPN model. Gelatin zymography was used to measure MMP-9/2 activities. Western blotting and immunohistochemistry were used to measure the expression of high-mobility group box-1 (HMGB-1), calcitonin gene-related peptide and ionized calcium-binding adapter molecule 1. Mechanical withdrawal was measured by von Frey hairs testing. Raw 264.7 cells and SH-SY5Y cells were cultured to investigate cell signaling in vitro. Here, we report that L-OHP-induced mechanical pain in mice with significant MMP-9/2 activation in dorsal root ganglion (DRG) neurons. MMP-9 inhibition or knockout alleviated the occurrence of CIPN directly. MMP-9/2 were released from macrophages and neurons in the DRG via the HMGB-1-toll-like receptor 4 (TLR4)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) axis, because MMP-9/2 activities could be reduced by macrophage scavengers or PI3Kγ knockout in CIPN mice. The in vitro data revealed that induced MMP-9 activity by recombinant HMGB-1 could be abolished by TLR4, PI3K or Akt inhibitors. Finally, it was shown that N-acetyl-cysteine (NAC) could reduce MMP-9/2 activities and attenuate CIPN effectively and safely. The HMGB-1-TLR4-PI3K/Akt-MMP-9 axis is involved in the crosstalk between macrophages and neurons in the pathological process of CIPN in mice. Direct inhibition of MMP-9 by NAC may be a potential therapeutic regimen for CIPN treatment.