大黄附子汤对重症急性胰腺炎小鼠肠道微皱褶细胞变化的影响

目的研究大黄附子汤对重症急性胰腺炎(SAP)小鼠肠道微皱褶细胞(M细胞)变化的影响，为大黄附子汤临床防治SAP提供理论基础。 方法选取40只健康SPF级C57BL/6J雄性小鼠，随机分为4组(每组10只)：空白对照组、大黄附子汤对照组、SAP组、大黄附子汤治疗组，其中SAP组和大黄附子汤治疗组分别以3.5 g/kg剂量腹腔注射20% L-精氨酸，空白对照组和大黄附子汤对照组注射等剂量的等渗盐水；于造模后12、24、36 h，空白对照组和SAP组给予等渗盐水0.2 mL，大黄附子汤对照组和治疗组给予大黄附子汤0.2 mL灌肠，均于造模完成48 h后处死取材，使用ELISA检测血清淀粉酶、内毒素、IL-1β及TNF-α含量，取回肠及胰腺组织行HE染色、评分，免疫组化染色检测M细胞特异性蛋白GP2并评分。 结果(1)一般情况：对照组腹腔注射后小鼠一般情况好，精神状态良好，能正常进水，四肢活动自如，行动未受影响；SAP组小鼠腹腔注射后一般情况差，精神萎靡，反应迟钝，行动迟缓，呼吸急促，拱背收腹，饮水减少。(2)SAP组淀粉酶、内毒素、IL-1β及TNF-α水平较对照组明显升高(P<0.05)；与SAP组进行对比，大黄附子汤治疗组血清淀粉酶、内毒素、IL-1β及TNF-α水平出现显著下降(P<0.05)。(3)HE染色：SAP组胰腺及回肠组织坏死严重，可见大量白细胞浸润。大黄附子汤治疗组胰腺及回肠组织轻度坏死，可见少量中性粒细胞等白细胞浸润。(4)免疫组化染色：SAP组与对照组相比GP2表达降低(P<0.05)；相较于SAP组，大黄附子汤治疗组GP2的表达水平升高(P<0.05)。 结论大黄附子汤治疗可改善作为肠道免疫应答起始的M细胞数量与功能，增强肠道免疫应答，减轻肠免疫屏障损伤，减少内毒素入血，改善SAP症状。     

基于合作对象探讨我国学术期刊专题/专栏建设

【目的】 了解学术期刊专题/专栏建设的现状,以切实发挥学术期刊专题/专栏建设的作用,为期刊的品牌建设、学术创新、影响力提升和办刊质量提高提供策略。【方法】 采用问卷调查法,对全国范围内397名专题/专栏合作对象(包括期刊主编、编委、审稿人、作者)进行调查,了解他们对期刊专题/专栏建设的态度和意见,从合作对象视角探讨影响学术期刊专题/专栏建设成功率和有效性的因素。【结果】 合作对象态度上,表示支持专题/专栏建设工作的比例较高(71.28%),但供稿率不高(43.37%),存在态度和行为分离的现象。排名前5的供稿率影响因素是期刊被本专业领域研究者认可、期刊被数据库收录情况、期刊影响力、期刊品牌、期刊的处理速度。最优的约稿方式是行业内的学术带头人联系约稿,其次是熟识的专家委托和期刊主编亲自联系进行约稿。合作对象最希望获得的帮助是稿件快速审理发表和确定选题方向。【结论】 为提高学术期刊专题/专栏建设质量,应进一步挖掘重要合作对象的作用,有针对性地选择高供稿率的合作对象;努力挖掘和利用影响合作对象供稿的因素,在期刊品牌建设、扩大影响力方面下功夫;优化约稿方式方法,重视行业学术带头人的作用;同时通过稿件快速审理发表、帮助确定选题并提供发表后推广等服务,提高合作对象对专题/专栏建设工作的认可度和参与度。     

尿道下裂的基因特点及其研究进展

尿道下裂是男性新生儿中常见的先天性泌尿系统畸形。主要是由阴茎和尿道发育异常引起的，是一种多因素疾病，个体差异明显。目前研究发现，多种因素均与尿道下裂有关，包括遗传因素、产前激素不足、母体胎盘因素及环境影响，因此，尿道下裂往往是多因素结合的产物。在过去的十年间，大量研究致力于揭示尿道下裂的遗传基因特点。这些研究包括骨形成蛋白（BMP）、成纤维细胞生长因子（FGF）、同源盒基因A（HOXA）等基因，涵盖了性别基因的转录、性激素的合成及相关基因的信号传导。尽管目前发现了大量尿道下裂相关基因，但仍需大样本病例临床对照研究明确这些基因的诊断效能及生物学意义。同时，随着测序技术的发展，外显子和全基因组测序也将揭示基因与基因、基因与环境的相互作用，更好地探索尿道下裂的分子机制，从而探寻合适分子标记物及治疗干预的靶点。综述这一领域的研究现状，并对一些与尿道下裂有关基因的研究进展进行探讨。     

Comparative study on the gastrointestinal- and immune- regulation functions of Hedysari Radix Paeparata Cum Melle and Astragali Radix Praeparata cum Melle in rats with spleen-qi deficiency,based on fuzzy matter-element analysis

ContextHedysari Radix Praeparata Cum Melle (HRPCM) and Astragali Radix Praeparata Cum Melle (ARPCM) are used interchangeably in clinics to treat spleen-qi deficiency (SQD) symptom mainly including gastrointestinal dysfunction and decreased immunity, which has unknown differences in efficacy.ObjectiveTo investigate the differences between HRPCM and ARPCM on intervening gastrointestinal- and immune-function with SQD syndrome.Materials and methodsAfter the SQD model was established, the Sprague–Dawley (SD) rats were randomly divided into nine groups (n = 10): normal; model; Bu-Zhong-Yi-Qi Pills; 18.9, 12.6 and 6.3 g/kg dose groups of HRPCM and ARPCM. Gastrointestinal function including d-xylose, gastrin, amylase vasoactive intestinal peptide, motilin, pepsin, H⁺/K⁺-ATPase, Na⁺/K⁺-ATPase, sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2) and immune function including spleen and thymus index, blood routine, interleukin (IL)-2, IL-6, interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), immunoglobulin (Ig) M, IgA, IgG and delayed-type hypersensitivity (DTH) were detected. Finally, the efficacy differences were analysed comprehensively by the fuzzy matter-element method.ResultsIn regulating immune, the doses differences in efficacy between HRPCM and ARPCM showed in the high-dose (18.9 g/kg), but there were no differences in the middle- and low- dose (12.6 and 6.3 g/kg); the efficacy differences were primarily reflected in levels of IL-6, IFN-γ, TNF-α and IgM in serum, and the mRNA expression of IL-6 and IFN-γ in the spleen. In regulating gastrointestinal, the efficacy differences were primarily reflected in the levels of D-xylose, MTL, and GAS in serum, and the mRNA and protein expression of SGLT1 and GLUT2 in jejunum and ileum.Discussion and conclusionsHRPCM is more effective than ARPCM on regulating gastrointestinal function and immune function with SQD syndrome. Therefore, we propose that HRPCM should be mainly used to treat SQD syndrome in the future.     

父亲生育年龄对子代预后的影响

早在1912年,Weinberg首次提出了父亲年龄的增长与子代的遗传缺陷有关。从此,人们开始意识到父亲年龄与子代预后有关联。近年,伴随着母亲生育年龄的增加,父亲的生育年龄也有所增加。纵观国内外的相关报道,除了父亲年龄对生育能力有影响外,父亲生育年龄对子代的影响可以分为近期影响和远期影响。对子代的近期影响包括早产、流产、...     

Association between clustering of cardiovascular risk factors and resting heart rate in Chinese population: a cross-sectional study

BACKGROUNDEpidemiologic studies have explored the association between a single cardiovascular risk factor (CVRF) and resting heart rate (RHR), but the research on the relation of multiple risk factors with RHR remains scarce. This study aimed to explore the associations between CVRFs clustering and the risk of elevated RHR.METHODSIn this cross-sectional study, adults aged 35–75 years from 31 provinces were recruited by the China PEACE Million Persons Projects from September 2015 to August 2020. We focused on seven risk factors: hypertension, diabetes mellitus, dyslipidemia, obesity, smoking, alcohol use, and low physical activity. Multivariate logistic regression was used to calculate odds ratios (OR) for elevated RHR (> 80 beats/min).RESULTSAmong 1,045,405 participants, the mean age was 55.67 ± 9.86 years, and 60.4% of participants were women. The OR (95% CI) for elevated RHR for the groups with 1, 2, 3, 4 and ≥ 5 risk factor were 1.11 (1.08–1.13), 1.36 (1.33–1.39), 1.68 (1.64–1.72), 2.01 (1.96–2.07) and 2.58 (2.50–2.67), respectively (P_trend < 0.001). The association between the CVRFs clustering number and elevated RHR was much more pronounced in young males than in other age-sex subgroups. Clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR than those comprising more behavioral risk factors. CONCLUSIONSThere was a significant positive association between the CVRFs clustering number and the risk of elevated RHR, particularly in young males. Compared clusters comprising more behavioral risk factors, clusters comprising more metabolic risk factors were associated with a higher risk of elevated RHR. RHR may serve as an indicator of the cumulative effect of multiple risk factors.

Over the past several years, the rapid development of smart wrist-worn devices has resulted in a convenient approach to monitoring resting heart rate (RHR) in daily life. RHR is becoming a promising indicator of cardiovascular health. Observational studies have shown that elevated RHR is associated with increased all-cause and cardiovascular mortality in populations with or without cardiovascular disease (CVD).^[1,2] Elevated RHR has also been found to be associated with cardiovascular risk factors (CVRFs), such as hypertension, diabetes mellitus, dyslipidemia, low physical activity and smoking, indicating its potential to reflect total cardiac risk.^[3–7] There is abundant epidemiologic evidence supporting the association between a single CVRF and RHR, but studies exploring associations between multiple CVRFs and RHR are limited. CVRFs tend to cluster within individuals, and several weak risk factors combined may result in a much higher risk than that due to a single strong risk factor. According to a cross-sectional survey in China, more than 45% of Chinese adults have two or more coexisting CVRFs.^[8] Thus, it is important to consider the situation of multiple CVRFs clustering. However, very few studies have analyzed the association between CVRFs clustering and RHR, and several aspects remain unknown. Firstly, prior studies mainly focused on the relation between metabolic risk factors and RHR.^[9–11] Behavioral risk factors such as smoking, physical activity and alcohol use have rarely been considered, even though these risk factors also have a significant effect on heart rate.^[3,5,7] Secondly, most studies merely dealt with the relation of CVRFs clustering number with RHR, while regarding each number of risk factors, different combinations of risk factors have not yet been considered before.^[9,12] It is important to consider different CVRF clustering patterns since some risk factors combined may lead to a higher risk of elevated RHR than others, even if the number of CVRFs is the same. Thirdly, prior studies did not assess associations stratified by sex and age. It has been well documented that RHR levels differ by sex and age. The RHR in women was on average 2–7 beats/min higher than that in men, and there was a decrease in the RHR with age.^[13,14] As such, whether the associations of CVRFs clustering with RHR varied between sex and age remains unclear. Taking advantage of the large sample size in our study, we are able to include a wider range of CVRFs (metabolic and behavioral risk factors), comprehensively evaluate the association between these CVRFs clustering and RHR, and further explore sex and age differences. This finding may inform us whether RHR can be used as a simple and efficient metric for the identification of high-risk individuals who require more intensive risk factor evaluation and earlier cardiovascular health monitoring in resource-constrained countries with substantial CVD burdens, such as China. To bridge this knowledge gap, we used data from the China PEACE Million Persons Projects, a nationwide screening project, to explore (1) the association between the number of CVRFs clustering and elevated RHR in the overall population and populations stratified by age and sex; and (2) the associations between different CVRFs clusters and the risk of elevated RHR in the overall population and populations stratified by sex.     

Idiopathic Membranous Nephropathy with Solitary Immunoglobulin A Deposition: A Case Report and a Review of the Literature

A 63-year-old man with an 8-year history of proteinuria was diagnosed with nephrotic syndrome, and a renal biopsy was performed. Light and electron microscopic analyses showed classic features of idiopathic membranous nephropathy (IMN). However, immunofluorescence tests revealed solitary polyclonal granular IgA deposition along the glomerular capillary walls, rather than IgG, which is often dominant in IMN. The combined use of corticosteroids and calcineurin inhibitor was noticeably effective in reducing proteinuria and improving edema in the current case. Two additional rare cases of IMN with solitary IgA deposition were reviewed, and long-term surveillance is still warranted to characterize its clinicopathological features and outcome.     

脊髓损伤患者认知损害及其神经影像学研究进展

脊髓损伤后认知损害的发生率较高,但因不易察觉而可能被忽略,且脊髓损伤后认知损害与多种因素相关,大脑结构功能的改变可能实际参与了认知损害过程,但具体机制尚不清楚。近年来学者采用神经影像学方法对脊髓损伤后脑结构功能改变进行研究,以期阐明脊髓损伤后认知损害机制。本文对脊髓损伤患者认知损害发病率及临床特征、评估方法、影响因素及神经影像学改变进行综述,旨在为脊髓损伤患者认知损害的预防及干预提供参考。     

新药研发项目成本管理面临的问题及对策

目的 意在提高对新药研发项目管理的重视,认识加强成本管理是新药研发的关键环节.方法 采用文献查阅法和网上信息搜集法等方法,分析了新药研发项目成本管理中遇到的一些问题.结论 提出了改善新药研发项目成本管理的几点对策.     

Rotenone,an environmental toxin,causes abnormal methylation of the mouse brain organoid's genome and ferroptosis

More and more reports have pointed out that rotenone, as an insecticide, has high neurotoxicity and reproductive toxicity to livestock and mammals. As a highly physiological correlation system of internal organs, quasi-organs have great potential in the fields of drug toxicity and efficacy test, toxicology research, developmental biology and so on. In this study, brain organs (mBOs) derived from mouse neural stem cells were used to investigate the effects of rotenone on the physiological activity and epigenetic modification of mBOs. At the same time, Rotenone could significantly stimulate the increase of the concentration of LPO, lactic acid and hydroxyl radical in mBOs, and inhibit the expression of neuronal marker Tuj1, CHAT, PAX6 and so on. Further analysis showed that Rotenonem could induce mitochondrial damage in mBOs. The results of qPCR and Western blot showed that Rotenone could up-regulate the expressions of ferroptosis promoting protein p53, Cox2 and so on, while inhibit the expressions of negative regulatory protein of ferroptosis GPX4, FTH1, SLC7A11. In addition, the results of RRBS-Seq sequencing showed that the methylation modification at DMR level in Rotenone-treated mBOs group was significantly higher than that in Ctrl group. The results of KEGG analysis showed that compared with Ctrl, the genes with hypermethylation of promoter and Genebody in Rotenone-treated mBOs were mainly located in the Neuro active ligand-receptor interaction signal transduction pathway. In summary, rotenone can significantly lead to abnormal methylation of mouse brain organs, and lead to the loss of normal physiological function of neurons by inducing ferroptosis.