Dysregulation

失调
  • 文章类型: Journal Article
    唐氏综合征患者的免疫系统失调被认为在许多临床表现的病理生理学中起主要作用。与纽约西奈山卫生系统的2605名患者对照队列相比,这项疾病自然史研究对1299名唐氏综合症患者的不同免疫相关诊断的患病率进行了综合评估。在过去的18年里,纽约。我们对本章接受诊断的几率进行了逐步分析,ICD-CM-10代码系统的子章节和诊断级别。我们的唐氏综合征队列中的个体诊断为炎症和自身免疫表现如斑秃的几率较高(OR6.06,p=0.01),其他败血症(OR4.79,p<0.001,紫癜和其他出血性疾病(OR2.31,p<0.001),和酒渣鼻(OR3.11,p<0.001)。他们还提出了较低的概率诊断为疱疹病毒感染(OR0.42,p=0.01),和病毒性疣(OR0.51,p=0.04)。我们认为唐氏综合症患者的免疫系统失调对传染病有影响,包括降低病毒性疾病的发病率和增加其严重程度。我们的数据还表明炎症和自身免疫介导的疾病,特别是皮肤,在唐氏综合症患者中加剧。最后,唐氏综合征患者人群中可能需要更多地关注非突发疾病,因为这些疾病也会极大地影响生活质量.
    Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 patient control cohort at the Mount Sinai Health System in New York, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, are exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life.
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  • 文章类型: Journal Article
    行为控制异常通常发生在普通人群和美国服役人员和退伍军人(SM/V)中。这种情况在SM/V中值得特别注意,特别是在部署之后。军事部署经常引起创伤后应激障碍(PTSD)和部署相关的轻度TBI创伤性脑损伤(TBI),可能导致行为失控的表现。
    检查PTSD症状严重程度之间的关联,部署相关的轻度创伤性脑损伤,SM/V之间的行为控制失调
    来自军事相关脑损伤联盟的长期影响-神经创伤联盟在SM/V(N=1,808)中的前瞻性纵向研究的二级横截面数据分析。
    单变量和多变量线性回归模型评估了PTSD症状严重程度之间的关联和相互作用效应,根据诊断和统计手册的创伤后应激障碍清单评估,第5版(PCL-5),和部署相关的轻度TBI对行为控制异常,适应人口统计,疼痛,社会支持,弹性,和一般的自我效能感。
    在我们样本中的1,808个人中,在单变量分析中,PTSD症状严重程度(B=0.23,95%CI:0.22,0.25,p<0.001)和部署相关的轻度TBI(B=3.27,95%CI:2.63,3.90,p<0.001)与行为控制异常显着相关。在多变量分析中,PTSD症状严重程度与部署轻度TBI之间的交互作用显着(B=-0.03,95%CI:-0.06,-0.01,p=0.029),表明轻度TBI对行为控制的影响在PCL-5评分>22.96的人群中不再显著。
    结果表明PTSD症状严重程度之间存在关联,部署相关的轻度TBI,SM/V之间的行为控制失调值得注意的是,对于PTSD症状严重程度较低的个体,部署相关的轻度TBI的影响显著.较高的社会支持分数与较低的失控有关,强调社会支持可能成为保护因素。一般自我效能感也与行为控制失调减少有关。
    UNASSIGNED: Behavioral dyscontrol occurs commonly in the general population and in United States service members and Veterans (SM/V). This condition merits special attention in SM/V, particularly in the aftermath of deployments. Military deployments frequently give rise to posttraumatic stress disorder (PTSD) and deployment-related mild TBI traumatic brain injury (TBI), potentially leading to manifestations of behavioral dyscontrol.
    UNASSIGNED: Examine associations among PTSD symptom severity, deployment-related mild traumatic brain injury, and behavioral dyscontrol among SM/V.
    UNASSIGNED: Secondary cross-sectional data analysis from the Long-Term Impact of Military-Relevant Brain Injury Consortium - Chronic Effects of Neurotrauma Consortium prospective longitudinal study among SM/V (N = 1,808).
    UNASSIGNED: Univariable and multivariable linear regression models assessed the association and interaction effects between PTSD symptom severity, as assessed by the PTSD Checklist for the Diagnostic and Statistical Manual, 5th edition (PCL-5), and deployment-related mild TBI on behavioral dyscontrol, adjusting for demographics, pain, social support, resilience, and general self-efficacy.
    UNASSIGNED: Among the 1,808 individuals in our sample, PTSD symptom severity (B = 0.23, 95% CI: 0.22, 0.25, p < 0.001) and deployment-related mild TBI (B = 3.27, 95% CI: 2.63, 3.90, p < 0.001) were significantly associated with behavioral dyscontrol in univariable analysis. Interaction effects were significant between PTSD symptom severity and deployment mild TBI (B = -0.03, 95% CI: -0.06, -0.01, p = 0.029) in multivariable analysis, indicating that the effect of mild TBI on behavioral dyscontrol is no longer significant among those with a PCL-5 score > 22.96.
    UNASSIGNED: Results indicated an association between PTSD symptom severity, deployment-related mild TBI, and behavioral dyscontrol among SM/V. Notably, the effect of deployment-related mild TBI was pronounced for individuals with lower PTSD symptom severity. Higher social support scores were associated with lower dyscontrol, emphasizing the potential for social support to be a protective factor. General self-efficacy was also associated with reduced behavioral dyscontrol.
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  • 文章类型: Preprint
    唐氏综合征患者的免疫系统失调被认为在许多临床表现的病理生理学中起主要作用。这项疾病自然史研究对纽约西奈山卫生系统的1299名唐氏综合征患者的队列中不同免疫相关诊断的患病率进行了综合评估,与2605名没有唐氏综合征的对照队列相比,在过去的18年里,纽约。我们对本章接受诊断的几率进行了逐步分析,ICD-CM-10代码系统的子章节和诊断级别。我们的唐氏综合征队列中的个体诊断为炎症和自身免疫表现如斑秃的几率较高(OR6.06,p=0.01),其他败血症(OR4.79,p<0.001,紫癜和其他出血性疾病(OR2.31,p<0.001),和酒渣鼻(OR3.11,p<0.001)。他们还提出了较低的概率诊断为疱疹病毒感染(OR0.42,p=0.01),和病毒性疣(OR0.51,p=0.04)。我们认为唐氏综合症患者的免疫系统失调对传染病有影响,包括降低病毒性疾病的发病率,并增加其严重程度。我们的数据还表明炎症和自身免疫介导的疾病,特别是皮肤,在唐氏综合症患者中加剧。最后,唐氏综合征患者人群中可能需要更多地关注非突发疾病,因为这些疾病也会极大地影响生活质量.
    Dysregulation of the immune system in individuals with Down syndrome is thought to play a major role in the pathophysiology of many clinical presentations. This natural history of disease study took a comprehensive evaluation of the prevalence of different immune related diagnoses in a cohort of 1299 patients with Down syndrome compared to a 2605 control cohort of patients without Down syndrome at Mount Sinai Health System in NY, NY over the past 18 years. We conducted a stepwise analysis of the odds of receiving a diagnosis at the Chapter, Sub-chapter and Diagnosis level of the ICD-CM-10 code system. Individuals in our Down syndrome cohort had higher odds of a diagnosis with inflammatory and autoimmune presentations such as Alopecia areata (OR 6.06, p = 0.01), Other sepsis (OR 4.79, p < 0.001, Purpura and Other hemorrhagic conditions (OR 2.31, p < 0.001), and Rosacea (OR 3.11, p < 0.001). They also presented with lower odds of a diagnosis of Herpesviral infection (OR 0.42, p = 0.01), and Viral warts (OR 0.51, p = 0.04). We posit that dysregulation of the immune system in individuals with Down syndrome has impact on infectious diseases, including lowering the incidence of viral disease, and increasing its severity. Our data also suggests inflammation and autoimmune mediated diseases, in particular of the skin, is exacerbated in individuals with Down syndrome. Finally, there may be a need for greater clinical attention to non-emergent conditions within the Down syndrome patient population as those can also greatly affect quality of life.
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  • 文章类型: Observational Study
    背景:红细胞(RBC)在储存过程中会带来有害后果。储存的RBC中的微小RNA(miRNA)失调可能代表储存损伤的潜在生物标志物。虽然白细胞减少可以防止对红细胞的损害,目前尚不清楚红细胞的白细胞减少是否会影响储存过程中miRNAs的失调。这项研究评估了miRNA对白细胞减少(LR)和非白细胞减少(NLR)RBC的任何改变的潜在作用,直到储存21天。
    方法:在这项前瞻性研究中,将30名男性志愿者的血液平均分为白细胞减少的红细胞(LR)和NLR红细胞(NLR)袋,并在4-60℃保存至第21天。在第0天和第21天定量选择的miRNA。Further,使用生物信息学工具分析选定的miRNA及其预测的靶基因(mRNA),并鉴定miRNA-mRNA调控关系。
    结果:三种miRNA的倍数变化值(miR-96-5p,miR-197-3p,miR-769-3p)在NLR红细胞中观察到(p<0.05)。在NLRRBC中观察到miR-150-5p和miR-197-3p的显著更高(p<.05)的表达水平,直到储存21天。Further,与mRNA定量的相关性证实了这些miRNA在功能途径富集分析中的调节作用.
    结论:在NLR红细胞中观察到较高水平的miRNA失调。从二氧化硅分析的验证表明miRNA在细胞凋亡中的调节作用,衰老,和红细胞相关信号通路。这表明储存的LRRBCs在输血后可能具有更好的体内存活和功能。然而,有必要对红细胞中miRNA进行体内研究以获得确凿的证据.
    Red Blood cells (RBCs) bring about harmful consequences during storage. MicroRNA (miRNA) dysregulation in stored RBCs could represent potential biomarkers of storage lesions. Although leukoreduction prevents damage to RBCs, it is uncertain whether leukoreduction of RBCs would impact the dysregulation of miRNAs during storage. This study evaluated the potential role of miRNAs for any alteration of leukoreduced (LR) and non-leukoreduced (NLR) RBCs till 21 days of storage.
    In this prospective study, thirty male volunteers\' blood was equally divided into leukoreduced RBCs (LR) and NLR RBC (NLR) bags and stored till Day 21 at 4-60c. Selected miRNAs were quantified on Days 0 and 21. Further, bioinformatic tools were used to analyze the selected miRNAs and their predicted target genes (mRNAs) and identify the miRNA-mRNA regulatory relationships.
    A significantly higher fold change values of three miRNAs (miR-96-5p, miR-197-3p, miR-769-3p) were observed in NLR RBCs (p < .05). A significantly higher (p < .05) expression levels of miR-150-5p and miR-197-3p were observed in NLR RBCs till 21 days of storage. Further, the correlation with mRNA quantification confirmed the regulatory role of these miRNAs upon functional pathway enrichment analysis.
    A higher level of dysregulation of miRNAs was observed in NLR RBCs. Validation from In-Silico analysis suggested the regulatory role of miRNAs in cell apoptosis, senescence, and RBC-related signaling pathways. This indicated that stored LR RBCs would likely have better in vivo survival and function following transfusion. However, an in vivo study of miRNA in RBCs is warranted for conclusive evidence.
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  • 文章类型: Journal Article
    乳腺癌患者和幸存者经常报告疲劳,情感,和认知障碍,这降低了各级职业的表现,使生活质量问题成为临床上相当关注的问题。这项研究的目的是评估整个放射治疗期间的注意力和情绪调节以及补充替代医学(CAM)的可能影响。
    57例单侧乳腺癌患者在参加这项双盲随机研究之前接受了手术和全身化疗。三分之二接受CAM(n=38),其余接受安慰剂(仅限携带者,n=19)。患者的注意力和焦虑在基线时进行生理测试,辐射期间的2周和4周以及辐射疗程结束后的1个月。
    两组患者的焦虑水平相似,在基线和放疗后无显著差异。在CAM患者中观察到注意力表现的长期显着恢复,伴随着焦虑水平的类似趋势,用眨眼概率来衡量。
    这项研究从生理上验证了乳腺癌幸存者中报告的注意力障碍;它描绘了常规CAM对注意力失调的有益后期效应。建议的非侵入性生理措施可以从生理上监测患者的心理和认知健康状况,并通过评估乳腺癌患者的应对能力以支持治疗计划来评估CAM对乳腺癌患者的有益作用。因此,结果对患者和幸存者的生活质量有潜在的临床意义.
    NIH,NCT02890316。2016年7月注册,http://www.ClinicalTrials.gov.
    Breast cancer patients and survivors frequently report fatigue, emotional, and cognitive disturbances, which reduce performance at all levels of occupation and make life quality issues a considerable clinical concern. The aim of this study is to evaluate attention and emotion regulation across radiotherapy period and the possible effects of complementary alternative medicine (CAM).
    Fifty-seven patients with unilateral breast cancer underwent surgery and systemic chemotherapy before participating in this double-blind randomized study. Two thirds were given CAM (n = 38) while the rest received placebo (carrier only, n = 19). Patients\' attention and anxiety were physiologically tested at baseline, 2 and 4 weeks during the radiation period as well as 1-month after the end of radiation session.
    Both groups showed similar levels of anxiety with no significant differences at baseline nor post-radiotherapy. Long-term significant recovery of attention performance was observed in the CAM patients, accompanied by a similar tendency in anxiety level, measured by the eye-blink probability.
    This study physiologically validates the attention impairment reported among breast cancer survivors; also, it depicted a beneficial late-effect of a routine CAM on attention dysregulation. The suggested non-invasive physiological measures can physiologically monitor patients\' psychological and cognitive well-being as well as evaluate the beneficial effect of CAM in breast cancer patients by assessing their coping ability to support the treatment plan. Thus, the results have potential clinical implications on patients\' and survivors\' quality of life.
    NIH, NCT02890316. Registered July 2016, http://www.ClinicalTrials.gov.
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  • 文章类型: Journal Article
    简介:基因组学和生物信息学是探索辐射对生物系统影响的不清楚方面的有用方法。辐照样品中的许多辐射诱导的变化是辐射后时间依赖性的。本研究旨在评估伽马射线对人Jurkat细胞的照射后效应。方法:辐射后6和24小时收集的样品的基因表达谱,以找到关键的差异表达基因和相关途径。样品由基因表达综合(GEO)提供并通过ClueGO分析。结果:确定了29个关键基因为重要的受影响基因,并引入了7类相关通路。CCNE2,PSMD11,CDC25C,ANAPC1,PLK1,AURKA,与超过6个途径相关的CCNB1与确定的途径组之一相关。结论:细胞保护通路与基因(HSPA5、HSPA8、HSP90B1、HMMR、CEBPB,RXRA,和PSMD11)与最小路径数有关。这项研究的发现对应于取决于辐射后时间的修复过程。这些基因似乎是进一步研究的合适候选者。
    Introduction: Genomics and bioinformatics are useful methods for exploring unclear aspects of radiation effects on biological systems. Many radiation-induced alterations in irradiated samples are post-radiation time-dependent. This study aims to evaluate the post-irradiation effects of the gamma ray on human Jurkat cells. Methods: Gene expression profiles of the samples harvested 6 and 24 hours after radiation to find the critical differential expressed genes and the related pathways. Samples are provided from Gene Expression Omnibus (GEO) and analyzed by ClueGO. Results: Twnety-nine critical genes were determined as the important affected genes and 7 classes of related pathways were introduced. CCNE2, PSMD11, CDC25C, ANAPC1, PLK1, AURKA, and CCNB1 that were associated with more than 6 pathways were related to one of the determined pathway groups. Conclusion: Cell protecting pathways were associated with the genes (HSPA5, HSPA8, HSP90B1, HMMR, CEBPB, RXRA, and PSMD11) which were related to the minimum numbers of pathways. The finding of this study corresponds to repair processes which depend on post-radiation time. It seems these sets of genes are suitable candidates for further investigation.
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  • 文章类型: Journal Article
    Adolescence often is characterized by the onset of social anxiety and risk taking; yet, not all youth are anxious and/or risk takers. There are several factors that may help differentiate youth with anxiety (e.g., threat sensitivity and emotion dysregulation) and youth who take risks (e.g., impulsivity and emotion dysregulation). We conducted a latent class analysis to identify groups of youth who differ in these processes, and then investigated group differences on the error-related negativity, an ERP that has been differentially associated with threat sensitivity and impulsivity.
    Youth (N = 1313, Mage = 11, range = 8-15 years) completed a survey assessing their emotion dysregulation, sensitivity to threat, and impulsivity. A subsample (N = 424) also completed a go/no-go task while EEG was recorded.
    Four groups were identified with differential levels of emotion dysregulation, sensitivity to threat, and impulsivity. Adolescents had greater odds than children of being in the High_Dysregulation/ThreatSensitivity or ModerateDysregulation/HighImpulsivity Groups in comparison to two other groups with lower scores. The High_Dysregulation/ThreatSensitivity Group had the largest ERN, while the ModerateDysregulation/HighImpulsivity Group had the smallest ERN. The ERN may be a potential biomarker to help distinguish between different profiles of adolescents who may be at risk for either anxiety or risk taking.
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  • 文章类型: Journal Article
    尽管自闭症谱系障碍(ASD)的自我调节受损(失调)引起了越来越多的意识,ASD中失调的神经机制远未定论。为了补充我们之前基于体素的形态测量结果,我们估计了皮质厚度,表面积,以及基于来自85名ASD和65名典型发展中的对照(TDC)男孩的结构性MRI图像的基于表面的形态计量学的局部回旋性指数,7-17岁。失调的水平是通过注意力的T得分的总和来衡量的,侵略,儿童行为清单上的焦虑/抑郁分量表。我们发现ASD和TDC在左上下颞回和左运动前皮层的失调和皮质折叠模式之间具有相似的关系。在右中额叶和右外侧眶额叶区域确定了皮质折叠模式失调的显着诊断。当考虑到失调水平时,ASD中比TDC更大的局部回旋指数在几个大脑区域的统计学意义消失了。在ASD和TDC之间共同和不同的神经相关基础的发现可能会促进将来有针对性的干预措施的发展。目前的工作还表明,自我调节的主体间变化可以解释与ASD相关的大脑形态差异的某种程度。可能表明失调是剖析ASD异质性的标准之一。
    Although impaired self-regulation (dysregulation) in autism spectrum disorder (ASD) garnered increasing awareness, the neural mechanism of dysregulation in ASD are far from conclusive. To complement our previous voxel-based morphometry findings, we estimated the cortical thickness, surface area, and local gyrification index based on the surface-based morphometry from structural MRI images in 85 ASD and 65 typically developing control (TDC) boys, aged 7-17 years. Levels of dysregulation were measured by the sum of T-scores of Attention, Aggression, and Anxiety/Depression subscales on the Child Behavior Checklist. We found both ASD and TDC shared similar relationships between dysregulation and cortical folding patterns in the left superior and inferior temporal gyri and the left premotor cortex. Significant diagnosis by dysregulation interactions in cortical folding patterns were identified over the right middle frontal and right lateral orbitofrontal regions. The statistical significance of greater local gyrification index in ASD than TDC in several brain regions disappeared when the level of dysregulation was considered. The findings of shared and distinct neural correlates underpinning dysregulation between ASD and TDC may facilitate the development of targeted interventions in the future. The present work also demonstrates that inter-subject variations in self-regulation may explain some extents of ASD-associated brain morphometric differences, likely suggesting that dysregulation is one of the yardsticks for dissecting the heterogeneity of ASD.
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  • 文章类型: Journal Article
    背景:阿尔茨海默病的发病机制与从转录组到细胞功能的不同水平的失调有关。这种复杂性需要考虑疾病的多个方面和独立策略的使用来进行疾病病因研究。已建立的著作更多地强调了基因调控网络的结构组织,而忽略了内部调控的变化。方法:采用不同于常用共表达网络分析的策略,这项研究调查了从正常状态到疾病状态过渡期间的转录失调。结果:97个基因被预测为失调基因,这也与阿尔茨海默病的临床结局有关。共表达和差异共表达分析都表明这些基因作为核心网络相互连接,并且在向疾病状态过渡的过程中它们的调节得到了加强。功能研究表明,失调的基因与衰老和突触功能有关。Further,我们检查了基因共表达的保守性,发现人类和小鼠的大脑可能具有不同的转录共调控,即使它们具有保守的基因表达谱。结论:总体而言,我们的研究揭示了通过影响衰老和突触功能相关基因与阿尔茨海默病进展相关的转录失调的核心网络;该基因调控在人类和小鼠大脑中是不保守的。
    Background: The pathogenesis of Alzheimer\'s disease is associated with dysregulation at different levels from transcriptome to cellular functioning. Such complexity necessitates investigations of disease etiology to be carried out considering multiple aspects of the disease and the use of independent strategies. The established works more emphasized on the structural organization of gene regulatory network while neglecting the internal regulation changes. Methods: Applying a strategy different from popularly used co-expression network analysis, this study investigated the transcriptional dysregulations during the transition from normal to disease states. Results: Ninety- seven genes were predicted as dysregulated genes, which were also associated with clinical outcomes of Alzheimer\'s disease. Both the co-expression and differential co-expression analysis suggested these genes to be interconnected as a core network and that their regulations were strengthened during the transition to disease states. Functional studies suggested the dysregulated genes to be associated with aging and synaptic function. Further, we checked the conservation of the gene co-expression and found that human and mouse brain might have divergent transcriptional co-regulation even when they had conserved gene expression profiles. Conclusion: Overall, our study reveals a core network of transcriptional dysregulation associated with the progression of Alzheimer\'s disease by affecting the aging and synaptic functions related genes; the gene regulation is not conserved in the human and mouse brains.
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  • 文章类型: Journal Article
    Among all the sequencing techniques, RNA sequencing (RNA-seq) has galloped with pace adopting the profiling of transcriptomic data in almost every biological analytics area like gene regulation study, development biology and clinical research. Recently the discovery of differentially expressed genes across different conditions has outshone the barrier of genetic & epigenetic regulations. The present work identified and analyzed differentially expressed novel long non-coding RNAs (lncRNAs) for breast cancer. A complex computational pipeline was adopted for the study which includes analysis of 18498 differentially expressed genes with 4114 up-regulated and 3475 down-regulated transcripts. The overexpression of lnc-MTAP (CDKN2B-AS1), lnc-PCP4 (DSCAM-S1), and lnc-FAM (H19) in breast cells suggests that these lncRNAs may have significant role to play in breast cancer. These results validated the relevance of the dysregulation pattern in cancer cells due to the presence of lncRNAs. The study further opens a new scope for experimental analysis to confirm the aberrant expression pattern of these lncRNAs which may act as potential bio-markers for the diagnosis and early detection of breast cancer.
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