类风湿关节炎合并骨关节炎病人血清anti-Sa、anti-CCP水平与骨关节损伤、全身炎症反应的相关性分析

目的:分析类风湿关节炎(RA)病人血清anti-Sa、anti-CCP抗体水平与其骨关节损伤、全身炎症反应的相关性。方法:选择RA合并骨关节损伤病人108例,根据血清anti-Sa、anti-CCP抗体水平分别列入高anti-Sa组和低anti-Sa组、高anti-CCP组和低anti-CCP组。比较各组病人WOMAC骨性关节炎指数、lysholms膝关节功能评分值,血清白细胞介素(IL)-1β、IL-6、IL-27、肿瘤坏死因子α(TNF-α)水平。采用Pearson检验评估有关指标的相关性。结果:高anti-Sa组、高anti-CCP组病人的WOMAC骨性关节炎指数明显高于低anti-Sa组(P<0.01),lysholms膝关节功能评分明显低于低anti-Sa组(P<0.01);血清中IL-1β、IL-6、IL-27、TNF-α的水平明显高于低anti-CCP组(P<0.01)。RA病人血清anti-Sa、anti-CCP抗体水平与骨关节损伤、全身炎症反应严重程度呈正相关关系(P<0.05~P<0.01),与lysholms膝关节功能评分呈负相关关系(P<0.01)。结论:RA病人血清中anti-Sa、anti-CCP抗体水平显著升高与关节损伤及全身炎症反应有一定的相关性,可作为临床判断病情活动性与骨关节损伤的参考指标。

Safety and in Vivo Anti-Inflammatory Activity of Ethanolic Extract of Ficus umbellata (Vahl.) Leaves

Toxicity is the totality of adverse effects, which can be functional and morphological lesions in a living organism, caused by a substance introduced in relatively high single doses or in small, repeated doses. The aim of this study was to assess the OECD-recommended acute oral toxicity and anti-inflammatory activity of ethanolic extract of Ficus umbellata leaves. Animals were given a single oral dose of 1000, 3000 and 5000 mg/Kg body weight (BW) of the extract. For the anti-inflammatory activity test, rats were given the ethanolic extract of F. umbellata leaves at doses of 100, 300 and 500 mg/Kg or aspirin® at a concentration of 100 mg/Kg PC orally, one hour before injection of 0.05 ml of 1% formalin under the plantar fascia of the rat’s right hind paw. Paw volume measurements were taken one, two and three hours after formalin injection, using an electronic caliper. After 14 days of observation, no deaths were observed in treated rats. The LD50 of ethanolic extract of Ficus umbellata leaf powder is greater than 5000 mg/Kg body weight. This extract has no significant effects on hematological parameters and on the main markers of nephrotoxicity and hepatotoxicity for a single dose of less than 5000 mg/Kg PC. It reduces formalin-induced edema. Evaluation of the percentage inhibition showed that the extract had greater anti-inflammatory activity at 3 hours after the start of the experiment. However, better inhibition of inflammatory oedema of the paw of rats treated with 500 mg/Kg was observed at 5 hours after the start of the experiment, with a percentage inhibition of 69.23 ± 1.02, compared with the reference group treated with aspirin® 100 mg/Kg, which showed an inhibition of 63.50 ± 0.98. These results show that F. umbellata leaves possess anti-inflammatory activity, which would justify their use in traditional African medicine to prevent or treat inflammation.

基于YOLOv5s-AntiUAV的反无人机目标检测算法研究

随着无人机的应用领域不断拓展,无人机的“黑飞”给公共安全造成严重损害。为解决侵入式无人机小目标在复杂飞行环境下的错检和漏检问题,提出基于YOLOv5s-AntiUAV的反无人机目标检测算法。首先,引入结合深度超参数卷积的Slim-Neck范式,增强算法特征提取能力并保持计算效率。其次,在骨干和颈部网络引入SPD-Conv模块,提高在低分辨率图像中小目标的检测性能。最后,用Alpha-CIoU替换YOLOv5s算法中的CIoU,增强算法泛用性。YOLOv5s-AntiUAV算法与YOLOv5s、SSD和Faster R-CNN算法在数据集Anti-UAV上的对比实验结果表明,改进算法的mAP@0.5值分别增长了1.1、12.1和4.9个百分点,凸显其实用性。由在VisDrone2019数据集上进行的迁移实验显示,相较于YOLOv5s算法,改进算法mAP@0.5值提升了4.5个百分点,表明其相较于原算法具有更强的鲁棒性。

Implications for Antigravity Tests of Dirac’s Negative Energy Antiparticles

P. A. M. Dirac conceived antimatter in 1928 as having negative energy by allowing a consistent representation of matter-antimatter annihilation into light. To achieve compatibility with special relativity, particle physics of the early 20th century made the theoretical assumption that antiparticles have positive energy, an assumption that remains in effect as of today. In this note we prove apparently for the first time a theorem stating that positive mass antiparticles violate Dirac’s particle-antiparticle annihilation into light. We then show the consequential unsettled character of the recent gravity test of the anti-Hydrogen atom due to the positive mass of its nucleus. We conclude by suggesting that a final scientific claim on matter-antimatter gravity requires tests on particles with clear antimatter character, such as the 1994 resolutory proposal for the comparative test of the gravity of very low energy electron and positron in horizontal flight on a supercooled vacuum tube.

31 Plant Species against Blood Feeding and Disease Vectors Insects: Beyond Anti-Insect Properties, Unvalued Opportunities and Challenges for Health and Sustainability

Plants with bioactive properties are greatly useful in preventing and controlling blood-sucking and disease-vector invertebrates, particularly in developing countries and low-income communities. Their application is a promising alternative to synthetic compounds whose use remains a health, environmental, and economic challenge. However, many are still unknown and unvalued, while others are becoming ignored and threatened. The main objective of this ethnobotanical study is to identify and characterize indigenous and locally grown plants against blood-sucking and disease-vector insects. Salient opportunities and challenges of using these plants are documented and discussed. Semi-structured interviews, using a prepared questionnaire, were conducted with 228 informants. The consensus index (CI) was calculated to analyze the reliability of the collected information. The identified 31 anti-insect plant species belong to 20 botanical families, four morphological categories, and six habitat types. They can be categorized as insecticidal plants (42% of the total), insect repellent (42% of the total), and both insecticidal and insect repellent (16% of the total). More than 54% of these are still abundant in the study area, while about 35.5% have become rare and difficultly accessible. Based on the numerical importance of related anti-insect plant species, the seven targeted blood-sucking insects range in the following decreasing order: Jiggers (16 species) > Fire Ants (9 species) > Flies (8 plants) > Mosquitoes (4 species) > Fleas (2 species) > Bedbugs (1 species) > lice (0 species). The three most commonly used plants, with the highest confirmation indices, are Tetradenia riparia (ICs = 0.712), Eucalyptus globulus subsp. maidenii (ICs = 0.302), and Solanum aculeastrum (ICs = 0.288). The antimicrobial role of many locally grown anti-insect plants and the multiple other associated valorization possibilities are ignored by most informants. Domesticating, propagating, protecting, and promoting the sustainable use of these plants would be an appropriate route for their conservation and continued availability.

Roles of Community Pharmacists in Screening and Disseminating of Information about Non-Steroidal Anti-Inflammatory Drugs Risks: Implications for Drug Safety Assessment

Background: The increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) both on prescription and over the counter raises a major global health concern because of the risks associated with their use if no proper guidance is given by the health care provider. This study assessed the roles of community pharmacists in screening and disseminating information about the risks associated with NSAID use in Zambia. Methodology: This was a national cross-sectional study in which a structured self-administered questionnaire was administered to 245 registered community pharmacists in Zambia. Stata/BE, version 15.1 (Stata Corporation, College Station, Texas, USA) and multivariate logistic regression model was used to determine factors associated with information dissemination about ADRs of NS-NSAIDs. Results: 231 of the 245 distributed questionnaires were returned giving a response rate of 94.3%. All (100%) participating community pharmacists claimed to have practiced dispensing NSAIDs. However, only 26 (11.0%) and 71 (30.8%) regularly screened for risk factor of selective COX-2 NSAIDS (SC2-NSAIDS) and non-selective NSAIDS (NS-NSAIDs) respectively. Information dissemination on adverse drug reactions (ADRs) of SC2-NSAIDS was regularly provided by only 22 (9.5%) of pharmacists while that of NS-NSAIDs was regularly provided by 49 (21.2%). In the multivariate logistic regression model, being the owner of a pharmacy (AOR: 5.4, CI: 1.84 - 16.4) was significantly associated with information dissemination about ADRs of NS-NSAIDs while an hour increase in the working hours per day (AOR: 0.9, CI: 0.64 - 0.95) was associated with less likelihood of information dissemination. Conclusion: Pharmacists working in community pharmacies in Zambia did not regularly screen and disseminate information about the risks associated with NSAID use. Therefore, pharmacists should be able to screen and monitor patients at risk and be aware of the majority of risk factors while dispensing NSAIDs to minimize the associated complications.

Phytochemical Screening, Study of Acute Toxicity and Hypoglycemic and Antihyperglycemic Activities of Silver Nanoparticles from Guibourtia tessmannii (Harms) J. Leonard (Caesalpiniaceae)

According to the World Health Organization, diabetes affects approximately 347 million people worldwide. Its management is not within the reach of all social classes, therefore medicinal plants are still the first resort for many populations in Africa. The biological material used in this study was the trunk bark of Guibourtia tessmannii. 50 g of trunk bark powder were decocted in 500 ml of distilled water for 5 minutes were carried out. The method used for the synthesis of silver nanoparticles (AgNps) was an organometallic bio-reduction of silver nitrate salts mediated by various secondary metabolites contained in the plant extract. The study of the toxicity acute was conducted according to guideline 423 of the OECD protocol. The pharmacological activities were each carried out with 28 female rats divided into 7 groups of four rats. It was a question for the hypoglycemic activity of administering various doses of silver nanoparticles and other substances to the rats thirty minutes after the carbohydrate intake and for the anti-hyperglycemic activity of administering the same substances to the rats thirty minutes before the carbohydrate intake. The extraction yield was 8.76%. Only the alkaloid test was negative. After acute toxicity study, the LD50 was greater than 2000 mg/kg. Blood sugar tests revealed that glibenclamide 5 mg/kg, which is the reference molecule, lowered blood sugar more than the other treatments applied in the other batches. It was followed by treatment with silver nanoparticles at a dose of 400 μg/kg in both tests. It was therefore concluded that silver nanoparticles from G. tessmannii are good for the formulation of improved traditional medicines and bring up their afficacity .

Contribution of Anti-p63 Antibodies in the Interpretation of Benign Label Prostatic Biopsies

Introduction: Prostate cancer is the second most common cancer in men. The diagnosis is most often based on the prostate biopsies’ analysis and on histological criteria recognizable on standard coloring. In some cases, the use of immunohistochemistry is important. Objectives: This paper aims to specify the p63 phenotypic profile of lesions diagnosed benign, with minimal suspect foci, difficult to interpret, HGPIN (high grade intraepithelial neoplasia) and LGPIN (low-grade prostatic intraepithelial neoplasia) and evaluate the manual technique of p63 immunohistochemistry. Patients and Method: This was a retrospective, descriptive study of prostate biopsies recorded in the PAC service of the HALD from January 1st, 2018 to December 31st, 2018. It was completed by a manual immunohistochemical study of the blocks enrolled from November 19th to December 4th, 2020 in the PAC department of the HPD. The studied parameters were: registry number, age, clinical stage, prostate volume, PSA level, microscopic appearance and p63 immunohistochemical profile. Results: Our study included 60 prostate biopsies. The ages of our patients varied from 45 to 77 years, with an average of 64.2 years and a standard deviation of 6.2. The majority of patients were at clinical stage cT2b (33%) with a prostate volume varying between 33.15 and 169.4 cc. The minimum value of PSA in our series is 5 ng/ml, the maximum being 100 ng/ml with an average level of 24.1 ng/ml and a standard deviation of 21.2. Our series included 50 adenomyomatous hyperplasias, 7 adenomyomatous hyperplasias associated with chronic prostatitis, 2 HGPIN and 1 LGPIN. After re-reading we found 5 discordant cases, which corresponded to minimal suspect foci (kappa = 0.5098). The p63 marking was informative in 53 cases, i.e. 88%, and non-informative in 7 cases, i.e. 12%. Among the uninformative markings, 2 were due to lack of tissue adhesion to the slides. Among the informative markings, 11 were negative. p63 immunohistochemistry was useful in all suspected foci and detected 6 other minimal foci of adenocarcinoma. Conclusion: The immunostaining with the anti-p63 antibody in the prostate cancer diagnosis is of considerable benefit. It made it possible to correct 11.3% of benign diagnosis in minimal malignant focus in our context. Despite the difficulties associated with the manual technique, it is possible to have an informative rate, similar to the automatic technique.

Evaluation of Serum Anti-Müllerian Hormone (AMH) Values for 28,016 Bulgarian Women: Prognostic Statistical Model of Age Specific AMH Declining

The present study aims to establish a relationship between serum AMH levels and age in a large group of women living in Bulgaria, as well as to establish reference age-specific AMH levels in women that would serve as an initial estimate of ovarian age. A total of 28,016 women on the territory of the Republic of Bulgaria were tested for serum AMH levels with a median age of 37.0 years (interquartile range 32.0 to 41.0). For women aged 20 - 29 years, the Bulgarian population has relatively high median levels of AMH, similar to women of Asian origin. For women aged 30 - 34 years, our results are comparable to those of women living in Western Europe. For women aged 35 - 39 years, our results are comparable to those of women living in the territory of India and Kenya. For women aged 40 - 44 years, our results were lower than those for women from the Western European and Chinese populations, close to the Indian and higher than Korean and Kenya populations, respectively. Our results for women of Bulgarian origin are also comparable to US Latina women at age 30, 35 and 40 ages. On the base on constructed a statistical model to predicting the decline in AMH levels at different ages, we found non-linear structure of AMH decline for the low AMH 3.5) the dependence of the decline of AMH on age was confirmed as linear. In conclusion, we evaluated the serum level of AMH in Bulgarian women and established age-specific AMH percentile reference values based on a large representative sample. We have developed a prognostic statistical model that can facilitate the application of AMH in clinical practice and the prediction of reproductive capacity and population health.

Quantification of Total Phenols, Total Flavonoids, Total Anthocyanins and Evaluation of Antioxidant and Antiradical Activities of Detarium Senegalense Extracts from Chad

The aim of the present work is to assess the value of Detarium Senegalense by determining the content of total phenols, total flavonoids and total anthocyanins, and by evaluating the free radical scavenging activity of Detarium Senegalense extracts. For this purpose, sequential extraction using solvents of increasing polarity was essential. The various extracts obtained underwent phytochemical and biochemical analyses. Phytochemical screening revealed the presence of flavonoids, alkaloids, tannins, polyphenols, anthocyanins and steroids/terpenes. Quantitative analysis of total polyphenols, total flavonoids and total anthocyanins yielded the following results: total flavonoids (0.803 ± 0029 mg EQ/100g P for acetone extract of roots and 0.871 ± 0.401 mg EQ/100g P for methanol extract of leaves);total polyphenols (23.298 ± 12.68 mg EAG/100g P for acetone extract of roots and 24.69 ± 0.49 401 mg EAG/100g P for methanol extract of leaves);total monomeric anthocyanins (44.697 ± 0.939 mg EC3G/100g P and 16.699 ± 0.193 mg EC3G/100g P respectively for acetone and methanol extracts of stem bark). DPPH free radical scavenging activity was 1.674 ± 0.023 mg/mL for the acetone extract and 0.934 ± 0.24 mg/mL for the methanol extract of roots. .

磁荷对Hayward-Anti-de Sitter黑洞的全息互信息的影响

Hayward黑洞是爱因斯坦引力非线性耦合一个携带磁荷的电磁场的解析解,是非线性磁单极子引力场的简并结构。一般情况下,黑洞的内部会存在奇点,而“非奇异”黑洞是一种内部没有奇点的黑洞。Hayward黑洞属于非奇异黑洞,此规则黑洞的对称性由磁势决定,带磁荷和不带磁荷的黑洞具有不同的微观结构。利用纠缠熵讨论磁荷对非奇异Hayward-Anti-de Sitter黑洞中全息互信息的影响。结果表明,随着条带宽度(子区域)的增加,2个渐进子系统纠缠增大,且全息互信息随磁荷的增加而降低。除此之外,存在临界磁荷使得全息互信息为零,此时对偶的子区域之间不存在纠缠,磁荷取不同值时,全息互信息消失的条带宽度临界值是不同的。

基于慢病毒介导的NLRP3过表达对艾灸调控实验性RA家兔关节滑膜液anti-CCP、RF水平的影响

目的观察艾灸对实验性类风湿性关节炎(RA)家兔的抗炎消肿作用,通过在RA家兔实验模型过表达由慢病毒载体介导的NOD样受体相关蛋白3(NLRP3),研究艾灸对其膝关节滑膜液中抗环瓜氨酸多肽抗体(anti-CCP)、类风湿因子(RF)、白细胞介素-18(IL-18)含量的影响及其NLRP3调控机制。方法日本大耳白兔30只,随机分为空白组、模型组、艾灸组、NLRP3过表达组、NLRP3阴性对照组,每组各6只动物。福氏完全佐剂(FCA)平均注入家兔双膝关节腔(0.5 mL·kg^(-1))。RA模型塑造后第3天及治疗后第10天,将NLRP3过表达慢病毒载体(Lv-NLRP3-GFP)10μL注入NLRP3过表达组兔双后膝关节腔,NLRP3阴性对照组家兔同法注入等量携带GFP的慢病毒载体(LvGFP)作对照。艾柱灸艾灸各组家兔双侧“肾俞”、“足三里”穴(5壮/穴/天,6天1疗程,疗程间间隔1天,3个疗程)。治疗后观测各家兔左、右后膝关节周长,ELISA法检测关节滑膜液中anti-CCP、RF、IL-18的含量。结果与空白组比较,模型组左、右膝关节周长增大,膝关节滑膜液anti-CCP、RF、IL-18含量显著升高(P<0.01);与模型组比较,艾灸组左、右膝关节周长缩小,膝关节滑膜液anti-CCP、RF、IL-18含量显著降低(P<0.01);与艾灸组相比,NLRP3过表达组左、右膝关节周长增大(P<0.05),膝关节滑膜液anti-CCP、RF、IL-18含量升高(P<0.05)。结论艾灸对实验性RA家兔具有抗炎效应,艾灸“肾俞”、“足三里”穴可显著降低RA家兔膝关节滑膜液中免疫效应因子anti-CCP、RF以及炎性细胞因子IL-18的含量,在NLRP3过表达的情况下其作用显著降低,提示艾灸抑制实验性RA家兔异常免疫功能,从而实现其抗炎调节作用可能与NLRP3的表达情况有密切关联。

Experimental study of the anti-inflammatory activity of some compounds in Berchemia lineata(L.)DC

Objective:To screen the anti-inflammatory monomeric compounds isolated from Berchemia lineata(L.)DC and explore the anti-inflammatory mechanism of some compounds based on NF-κB signaling pathway.Methods:LPS was used to induce RAW264.7 to establish a model of cellular inflammatory reaction.CCK-8 method was used to detect the effect of monomer compounds on the activity of RAW264.7 cells.The release of nitric oxide(NO)in the superneant was measured by Griess method,and NO inhibition rate was calculated.The anti-inflammatory activity gradient of some monomeric compounds was also measured.The effects of monomer compound 21 on the secretion of IL-6,TNF-α,NF-κB,COX-2 and iNOS induced by LPS were detected by ELISA.Results:The concentration of monomer compound of Berchemia lineata(L.)DC.was 50μmol/L,and it was administered for 24 h.The results showed that anthraquinone compound No.19 had obvious drug toxicity,while other compounds had weak or no obvious drug toxicity.The concentration was 50μmol/L,and the drug was administered for 12 h.The results showed that all the monomer compounds could inhibit the release of NO to varying degrees,and the highest NO inhibition rate was over 90%,which showed obvious anti-inflammatory activity.NO inhibition rate of No.01 new skeleton compound can reach 70.81%.The results of anti-inflammatory activity gradient showed that the monomer compound of Berchemia lineata(L.)DC.could inhibit the release of NO in a dose-dependent manner.The results of ELISA showed that phenolic compound 21 could inhibit the secretion of IL-6,TNF-α,NF-κB,COX-2 and iNOS in RAW264.7 cells.Conclusion:The monomer compound of Berchemia lineata(L.)DC.has a certain anti-inflammatory activity,among which flavonoids and bibenzyl components isolated from this plant for the first time may be the material basis for its anti-inflammatory activity.The simple phenolic monomer compound 21 may play an anti-inflammatory role by regulating NF-κB signaling pathway.

联合检测ANuA、Anti-ds-DNA、anti-P和Anti-sm在SLE伴肾损害患者中的诊断价值

目的 探究抗核小体(ANuA)、抗双链DNA(Anti-ds-DNA)、抗核糖体P蛋白(anti-P)和抗Sm抗体(Anti-sm)联合检测在系统性红斑狼疮(SLE)伴肾损害患者中的诊断价值。方法 选取2019年1月至2022年4月黄山市人民医院收治的SLE患者163例为研究对象,根据患者是否合并肾损害分为SLE组(n=55)与SLE伴肾损害组(n=108)。收集两组患者血清进行ANuA、Anti-ds-DNA、anti-P和Anti-sm检测,比较两组上述抗体单一及联合检测的阳性率,并绘制ROC曲线分析上述抗体指标对SLE伴肾损害的诊断价值。结果 SLE组Anti-ds-DNA、Anti-sm抗体单一及联合检测阳性率均高于SLE伴肾损害组,差异均具有统计学意义(χ^(2)=18.360、10.513、8.010,P<0.05);SLE组ANuA、anti-P检测阳性率均低于SLE伴肾损害组,差异均具有统计学意义(χ^(2)=7.094、4.281,P<0.05)。多因素Logistic回归分析显示,ANuA(β=2.284,OR=9.816)、Anti-ds-DNA(β=0.749,OR=2.115)、anti-P(β=1.386,OR=3.999)和Anti-sm(β=0.475,OR=1.608)是SLE伴肾损害的独立影响因素(P<0.05)。ROC曲线显示,ANuA、Anti-ds-DNA、anti-P和Anti-sm四者联合检测时,预测SLE伴肾损害的AUC为0.911,敏感性、特异性分别为89.0%、92.6%,优于单一检测(P<0.05)。结论 ANuA、Anti-ds-DNA、anti-P和Anti-sm都与SLE伴肾损害有关,联合检测ANuA、Anti-ds-DNA、anti-P和Anti-sm对于提高SLE伴肾损害的诊断准确性具有重要价值。

Primary Characterization of a Novel Soymilk-Cashew Fermented with an Improving of Its Antioxidant and Anti-Inflammatory Contents

Cashew nut (Anacardium occidental) milk was included as a functional ingredient in soybean (Glycine max L.) milk at 20/80% and was fermented comparatively to commercial yogurt starters by two strains TC6 and A4 (recently isolated from two Ivorian highly flavored neglected traditional staple foods (beer and garlic)) identified as Weissella paramesenteroides and Enterococcus faecalis, after the screening of their probiotic, antioxydant and anti-inflammatory potentialities, respectively. The primary characterization of these plant-milks showed a strong improvement in their sensory, antioxidant and anti-inflammatory abilities. While TC6 from traditional beer Tchapalo increases anti-inflammatory activity by almost eighteen times, A4 isolated from garlic increases antioxidant activity by two times. Due to their aromatic and organosensory potentialities certainly, milks L138, L180 and 130 fermented respectively by the combination of TC6 and A4, TC4 alone and A4 alone were the most appreciated than the plant-milk fermented by the two strains of commercial yogurt. These probiotics, anti-oxidant and anti-inflammatory plant-milks should be further characterized in terms of their biological activities and tested in animal models to confirm their nutrition-health claims.

Anti-CD19Fab-(CP)_(3)新型二聚化抗体的构建及靶向性观察

目的构建并表达Anti-CD19Fab-(CP)_(3)二聚化抗体,鉴定其蛋白分子量及相对含量并观察其靶向性。方法通过基因克隆技术构建原核表达载体PAYZ-Anti-CD19Fab-(CP)_(3)及阳性对照质粒PAYZ-Anti-CD19Fab-(CPP)_(3),将质粒转化至大肠杆菌16C9中进行表达。表达产物经过透析及Protein G亲和层析柱纯化,采用SDS-PAGE电泳法及液相串联质谱法(LC-MS)鉴定Anti-CD19Fab-(CP)_(3)二聚化抗体分子量及相对含量;采用流式细胞术检测二聚化抗体与CD19^(+)B系淋巴瘤Raji细胞的结合能力以及二聚化抗体对CD19鼠源亲本全抗的竞争能力。结果成功构建并表达Anti-CD19Fab-(CP)_(3),所得产物纯化后经SDS-PAGE及LC-MS法鉴定其主要成分为二聚化抗体,含量为76.2%;Anti-CD19Fab-(CP)_(3)二聚化比例高于对照Anti-CD19Fab-(CPP)3,差异有统计学意义(P<0.05)。同浓度下,与Anti-CD19Fab-(CPP)_(3)及Anti-CD19Fab相比,Anti-CD19Fab-(CP)_(3)对Raji细胞的结合能力更强,亲和力更好,差异有统计学意义(P均<0.05)。结论通过在Fab的CH1尾端引入(CP)_(3)的改构方式可有效形成高比例二聚化抗体,显著提高抗体对靶细胞的靶向性,未来可应用于多价抗体及相关药物研发。

Risk of Autism Spectrum Disorder According to the Dose and Trimester of Exposure to Antiseizure Medications: A Systematic Review and Meta-Analysis

Background: The association between prenatal exposure to antiseizure medications (ASM) and autism spectrum disorder has been documented. This study sought to examine and synthesize evidence from studies that have evaluated these associations, with particular focus on the trimester of pregnancy and dosage of exposure. Methodology: PubMed, Embase, and PsycINFO databases were searched following strict inclusion/exclusion criteria. 10 studies were recruited involving children born to mothers with epilepsy who took ASM during pregnancy as cases, and those with epilepsy who did not take any ASM in pregnancy. Results: The relative risk of developing ASD among children exposed to valproic acid (RR, 3.90 [95% CI: 2.36 - 6.44], p < 0.006), was twice higher than that of carbamazepine (RR, 1.65 [95% CI: 0.62 - 4.37], p < 0.0001), or lamotrigine (RR, 1.60 [95% CI: 0.77 - 3.32], p = 0.006). The trimester of exposure and dosage of ASM administered were not significant. Conclusion: In summary, prenatal exposure to ASM increased the risk of developing ASD in children. The relative risk was twice as high in those exposed to valproic acid compared to those exposed to carbamazepine or lamotrigine. Trimester of pregnancy and dosage of ASM used by the mothers were not significant.

作为反垄断救济措施的数字平台互操作义务

作为反垄断救济措施的数字平台互操作义务,是解决当前数字平台封禁行为的重要方式,既能维持现有符合市场特征的市场结构,又能将数字平台内部的网络效应外部化,允许市场竞争者公平共享网络效应产生的效率。通过降低市场进入壁垒恢复市场的有效竞争,避免用户、数据等价值要素聚集于少数数字平台。不论是作为反垄断事前监管措施,还是作为反垄断事后救济措施,数字平台互操作义务都有较好的适用基础和空间。结合我国目前肯定性调整方法规定不足的现实情况,数字平台互操作义务可能适用的情形也比较清晰,主要是针对数字平台既有反竞争性的互操作安排。实施时应当明确以基线标准作为实施的限度,严格秉持依法、审慎、积极和协同的理念。以公平原则、比例原则为义务设计的基本原则,对互操作义务的范围、标准以及监管等各方面内容予以科学设定。

anti-FⅩa对服用利伐沙班抗凝的NVAF患者出血事件的预测价值

目的探讨抗活化因子Ⅹ活性试验(anti-FⅩactivityassay,anti-FⅩa)对服用利伐沙班抗凝的非瓣膜性心房颤动(non-valvular atrial fibrillation,NVAF)患者出血事件的预测价值。方法选取2020年1月至2022年1月台州市第一人民医院收治的190例服用利伐沙班抗凝的NVAF患者,根据患者年龄将其分为<65岁组(40例)、65~75岁组(52例)和>75岁组(98例)。以发色底物法进行anti-FⅩa检测,测定利伐沙班的血药浓度。采用受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)分析anti-FⅩa对出血事件的预测效能,采用Kaplan-Meier法进行生存分析。结果随着年龄的增加,患者利伐沙班峰值和谷值浓度及出血事件发生率均逐渐升高(P<0.05)。发生出血事件患者的峰值和谷值浓度均显著高于未发生出血事件患者(P<0.05)。峰值浓度对总体人群、65~75岁组、>75岁组患者出血事件预测的临界值分别为186.43ng/ml、201.18ng/ml和212.63ng/ml时,敏感度分别为81.62%、81.82%和91.89%;谷值浓度的预测临界值分别为34.36ng/ml、36.72ng/ml和38.42ng/ml时,敏感度分别为83.67%、90.91%和94.59%,但特异性均较低。以38.42ng/ml为谷值浓度的临界值,随访90d时谷值浓度高于临界值的患者出血事件风险大于低于临界值的患者,且出血事件随时间延长呈加重趋势(P<0.05)。结论高龄和发生出血事件患者的利伐沙班峰值和谷值浓度均升高,而谷值浓度的升高可预测90d内出血事件发生风险。

丹参总酚酸联合anti-PD-L1调控髓源性巨噬细胞浸润抑制乳腺癌发生发展

目的探究丹参总酚酸(total salvianolic acid,TSA)联合anti-PD-L1通过调控髓源性巨噬细胞瘤内浸润抑制乳腺癌的发生发展。方法构建E0771乳腺癌皮下肿瘤模型。25只小鼠随机分为空白组、模型组、TSA组(TSA 10 g·kg^(-1)),anti-PD-L1组(anti-PD-L110 mg·kg^(-1)),TSA联合anti-PD-L1组(TSA 10 g·kg^(-1)+anti-PD-L110 mg·kg^(-1))。TSA组每日灌胃给药,anti-PD-L1每3天1次腹腔注射,连续给药14 d。记录小鼠肿瘤体积变化及肿瘤、肝脏及脾脏重量。ELISA检测小鼠血浆中IL-6,MCP-1的含量,qPCR检测cxcl1,cxcl2,cxcl3,ccl2,gm-csf mRNA的表达,流式、免疫组化检测小鼠肿瘤、淋巴中髓源性巨噬细胞浸润情况,流式检测淋巴、脾脏CD4+T细胞、CD8+T细胞数量变化。结果与模型组相比,TSA,anti-PD-L1,TSA联合anti-PD-L1均可抑制E0771乳腺癌生长,减少IL-6、MCP-1分泌,降低cxcl1,cxcl2,cxcl3,ccl2,gm-csf mRNA表达,抑制髓源性巨噬细胞向肿瘤的募集,增加淋巴及脾脏内CD4+T细胞、CD8+T细胞数量,TSA联合anti-PD-L1治疗效果更佳显著。结论TSA联合anti-PD-L1显著抑制E0771乳腺癌皮下瘤发生发展进程,可能通过抑制髓源性巨噬细胞向肿瘤浸润,增强机体免疫效应发挥作用。