pol Gene Products, Human Immunodeficiency Virus

  • 文章类型: Journal Article
    HIV-1大流行,跨越四十年,对全球公共卫生构成重大挑战。本研究旨在了解太原市新报告HIV感染的分子传播特征。山西省,中国,分析输电网络的亚型特征和风险因素,为精准预防和干预措施提供科学依据。从2021年至2023年居住在太原的新诊断HIV-1患者中收集了720个样本。对HIV-1pol基因的部分基因进行测序可获得多个序列,并进行分析其亚型和分子传播网络。在样本中,获得了584条pol序列,揭示了17种HIV-1亚型,CRF07_BC(48.29%),CRF01_AE(31.34%),CRF79_0107(7.19%)为优势亚型。使用1.5%的遗传距离阈值,从313个pol基因序列中产生49个分子传递簇。单因素分析显示HIV传播分子网络在HIV亚型和户籍方面存在显著差异(p<0.05)。多因素logistic回归分析显示CRF79_0107亚型及其迁移者在HIV传播网络中与较高比例的序列相关。这些发现为制定局部HIV特异性干预策略提供了科学依据。
    The HIV-1 pandemic, spanning four decades, presents a significant challenge to global public health. This study aimed to understand the molecular transmission characteristics of newly reported HIV infections in Taiyuan, Shanxi Province, China, to analyze the characteristics of subtypes and the risk factors of the transmission network, providing a scientific basis for precise prevention and intervention measures. A total of 720 samples were collected from newly diagnosed HIV-1 patients residing in Taiyuan between 2021 and 2023. Sequencing of partial genes of the HIV-1 pol gene resulted in multiple sequence acquisitions and was conducted to analyze their subtypes and molecular transmission networks. Out of the samples, 584 pol sequences were obtained, revealing 17 HIV-1 subtypes, with CRF07_BC (48.29%), CRF01_AE (31.34%), and CRF79_0107 (7.19%) being the dominant subtypes. Using a genetic distance threshold of 1.5%, 49 molecular transmission clusters were generated from the 313 pol gene sequences. Univariate analysis showed significant differences in the HIV transmission molecular network in terms of HIV subtype and household registration (p < 0.05). Multivariate logistic regression analysis showed that CRF79_0107 subtype and its migrants were associated with higher proportions of sequences in the HIV transmission network. These findings provide a scientific foundation for the development of localized HIV-specific intervention strategies.
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  • 文章类型: Journal Article
    人类免疫缺陷病毒1型CRF59_01B,2013年在中国确定,已在全国范围内检测到,在广州及其附近地区表现出明显的高患病率。这项研究旨在揭示其起源和迁移。建立了一套数据集,纳入广州和公共数据库中所有可用的CRF59_01Bpol基因序列及其元数据。贝叶斯系统地理分析表明CRF59_01B起源于深圳,邻近的城市广州,大约在1998年,后验概率为0.937。分子网络分析检测到1131个传输链路,并显示出极高的聚类率(78.9%)。大量的城市间传输(26.5%,300/1131)在深圳和广州之间观察到,而区域间的传播将广州与中国南方(46)和西南(64)联系起来。广州的中心是CRF59_01B传输的枢纽,包括深圳流入(3.57事件/年)和广州郊区流出(>2事件/年)。大规模分析显示,从深圳到广州(5.08事件/年)和华北(0.59事件/年)的迁移显著,并从广州传播到中部(0.47个事件/年),东部(0.42个事件/年),南方(0.76个事件/年),西南地区(0.76个事件/年)和深圳(1.89个事件/年)。深圳和广州是CRF59_01B流通的发源地和枢纽,强调城市间合作和数据共享,以限制其在全国范围内的传播。
    Human immunodeficiency virus type 1 CRF59_01B, identified in China in 2013, has been detected nationwide, exhibiting notably high prevalence in Guangzhou and its vicinity. This study aimed to unravel its origin and migration. A data set was established, incorporating all available CRF59_01B pol gene sequences and their metadata from Guangzhou and the public database. Bayesian phylogeographic analysis demonstrated that CRF59_01B originated in Shenzhen, the neighboring city of Guangzhou, around 1998 with posterior probability of 0.937. Molecular network analysis detected 1131 transmission links and showed a remarkably high clustering rate (78.9%). Substantial inter-city transmissions (26.5%, 300/1131) were observed between Shenzhen and Guangzhou while inter-region transmissions linked Guangzhou with South (46) and Southwest (64) China. The centre of Guangzhou was the hub of CRF59_01B transmission, including the inflow from Shenzhen (3.57 events/year) and outflow to the outskirts of Guangzhou (>2 events/year). The large-scale analysis revealed significant migration from Shenzhen to Guangzhou (5.08 events/year) and North China (0.59 events/year), and spread from Guangzhou to Central (0.47 events/year), East (0.42 events/year), South (0.76 events/year), Southwest China (0.76 events/year) and Shenzhen (1.89 events/year). Shenzhen and Guangzhou served as the origin and the hub of CRF59_01B circulation, emphasizing inter-city cooperation and data sharing to confine its nationwide diffusion.
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  • 文章类型: Journal Article
    目的:本研究的目的是对南京地区新诊断HIV-1个体的分子传播网络和传播耐药(TDR)模式进行综合分析。
    方法:收集2019年至2021年南京初诊HIV患者的血浆样本。HIVpol基因被扩增,得到的序列用于确定TDR,鉴定病毒亚型,构建分子传输网络。采用Logistic回归分析研究与分子传播集群相关的流行病学特征。
    结果:从新诊断的个体中成功提取了1161个HIVpol序列,每个伴随着可靠的流行病学信息。分析显示存在多种HIV-1亚型,CRF07_BC(40.57%)和CRF01_AE(38.42%)最为普遍。此外,鉴定出其他6种亚型和独特的重组形式(URFs).在研究期间,新诊断病例中TDR的患病率为7.84%。采用1.50%的遗传距离阈值,分子传输网络的构建导致了137个簇的识别,包含613个节点,约占病例的52.80%。多变量分析表明,这些群体中的个体更有可能年龄≥60岁,失业,基线CD4细胞计数≥200个细胞/mm3,并感染CRF119_0107(P<0.05)。此外,对较大集群的分析表明,年龄≥60岁的个体,农民,那些没有TDR的,感染CRF119_0107的个体更有可能是这些集群的一部分。
    结论:这项研究揭示了南京地区HIV局部传播的高风险和高TDR患病率,特别是CRF119_0107的快速传播。对于本研究中确定的分子传播集群实施有针对性的干预措施对于有效控制HIV流行至关重要。
    OBJECTIVE: The objective of this study was to conduct a comprehensive analysis of the molecular transmission networks and transmitted drug resistance (TDR) patterns among individuals newly diagnosed with HIV-1 in Nanjing.
    METHODS: Plasma samples were collected from newly diagnosed HIV patients in Nanjing between 2019 and 2021. The HIV pol gene was amplified, and the resulting sequences were utilized for determining TDR, identifying viral subtypes, and constructing molecular transmission network. Logistic regression analyses were employed to investigate the epidemiological characteristics associated with molecular transmission clusters.
    RESULTS: A total of 1161 HIV pol sequences were successfully extracted from newly diagnosed individuals, each accompanied by reliable epidemiologic information. The analysis revealed the presence of multiple HIV-1 subtypes, with CRF 07_BC (40.57%) and CRF01_AE (38.42%) being the most prevalent. Additionally, six other subtypes and unique recombinant forms (URFs) were identified. The prevalence of TDR among the newly diagnosed cases was 7.84% during the study period. Employing a genetic distance threshold of 1.50%, the construction of the molecular transmission network resulted in the identification of 137 clusters, encompassing 613 nodes, which accounted for approximately 52.80% of the cases. Multivariate analysis indicated that individuals within these clusters were more likely to be aged ≥ 60, unemployed, baseline CD4 cell count ≥ 200 cells/mm3, and infected with the CRF119_0107 (P < 0.05). Furthermore, the analysis of larger clusters revealed that individuals aged ≥ 60, peasants, those without TDR, and individuals infected with the CRF119_0107 were more likely to be part of these clusters.
    CONCLUSIONS: This study revealed the high risk of local HIV transmission and high TDR prevalence in Nanjing, especially the rapid spread of CRF119_0107. It is crucial to implement targeted interventions for the molecular transmission clusters identified in this study to effectively control the HIV epidemic.
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  • 文章类型: Journal Article
    目的:阐明湖南省HIV-2的流行病学特征,中国,利用序列分析。
    方法:湖南省13例HIV-2感染者,中国,从2017年到2023年被纳入这项研究。进行了HIV-2env和pol区域的扩增,其次是Sanger测序。进行了系统发育和分子传输网络分析,以描绘分子特征和传输动力学。
    结果:所有14个人通过异性性交感染HIV-2,包括7名男性和7名女性,平均年龄为58岁。其中,确定了三对夫妇(HN001和HN013,HN010和HN011,HN008和HN009),以及据报道受试者HN004的商业性活动参与。值得注意的是,受试者HN001、HN003、HN008和HN010在与受试者HN004相同的地点从事商业性活动。pol基因的系统发育分析表明,所有受试者的序列与冈比亚的参考序列(A型)非常接近。采用1.5%的遗传距离阈值,14个受试者中有8个形成了分子传输网络,将HN002和HN004标识为中心节点。
    结论:2017年至2023年,湖南省所有HIV-2感染者,中国,通过可识别的途径获得病毒,表明它们之间有相似的HIV-2毒株传播。
    OBJECTIVE: To elucidate the epidemiological features of HIV-2 in Hunan Province, China, utilizing sequence analysis.
    METHODS: Thirteen individuals diagnosed with HIV-2 infection in Hunan Province, China, from 2017 to 2023 were included in this study. Amplification of HIV-2 env and pol regions was conducted, followed by Sanger sequencing. Phylogenetic and molecular transmission network analyses were performed to delineate molecular features and transmission dynamics.
    RESULTS: All 14 individuals contracted HIV-2 through heterosexual intercourse, comprising 7 males and 7 females, with a median age of 58 years. Among them, three couples (HN001 and HN013, HN010 and HN011, HN008 and HN009) were identified, along with commercial sexual activity engagement reported for subject HN004. Notably, subjects HN001, HN003, HN008, and HN010 engaged in commercial sexual activities at the same location as subject HN004. Phylogenetic analysis of the pol gene revealed close proximity of sequences from all subjects to reference sequences from Gambia (Sub-type A). Employing a genetic distance threshold of 1.5 %, eight out of the 14 subjects formed a molecular transmission network, with HN002 and HN004 identified as central nodes.
    CONCLUSIONS: From 2017 to 2023, all HIV-2-infected individuals in Hunan Province, China, acquired the virus through identifiable routes, indicating transmission of similar HIV-2 strains among them.
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  • 文章类型: Journal Article
    目的:评估广西接受ART治疗的HIV-1感染者的耐药性概况和决定因素。
    方法:样本和数据来自广西14个城市的HIV-1感染者,在ART后经历病毒学失败。对HIV-1pol基因进行测序,然后使用斯坦福大学HIV耐药数据库分析耐药突变.采用Logistic回归分析确定与HIV耐药和死亡率相关的潜在危险因素。
    结果:本研究包括总共8963个具有pol序列的个体。HIV-1耐药(HIVDR)的总体患病率为42.43%(3808/8963),显示从2016年至2023年的59.62%下降至41.40%。年龄≥50岁等因素,男性,汉族,教育水平较低,包括工人在内的职业,农民和儿童,艾滋病,治疗前CD4T细胞计数<200细胞/mm3,感染CRF01_AE和CRF55_01B亚型,和ART方案拉米夫定/齐多夫定/奈韦拉平对HIVDR的易感性更高。常见突变为M184V(17.38%)和K103N(22.14%)。此外,M184V的患病率,S68G,M41L和G190A在汉族和壮族之间存在差异。因素包括年龄,性别,种族,教育水平,职业,感染途径,临床分期,病毒载量,子类型,ART方案和HIVDR显示与死亡率显著相关。
    结论:导致广西HIV-1ART个体耐药的因素似乎非常复杂。持续加强耐药性监测势在必行,伴随着ART方案的优化,以有效地减轻病毒学故障。
    To assess the profiles and determinants of drug resistance in HIV-1-infected individuals undergoing ART in Guangxi.
    Samples and data were collected from HIV-1-infected individuals experiencing virological failure post-ART from 14 cities in Guangxi. Sequencing of the HIV-1 pol gene was conducted, followed by analysis for drug resistance mutations using the Stanford University HIV Drug Resistance Database. Logistic regression was employed to identify potential risk factors associated with both HIV drug resistance and mortality.
    A total of 8963 individuals with pol sequences were included in this study. The overall prevalence of HIV-1 drug resistance (HIVDR) was 42.43% (3808/8963), showing a decrease from 59.62% to 41.40% from 2016 to 2023. Factors such as being aged ≥50 years, male, Han nationality, lower education levels, occupations including workers, peasants and children, AIDS, pre-treatment CD4 T cell counts <200 cells/mm3, infection with CRF01_AE and CRF55_01B subtypes, and ART regimen lamivudine/zidovudine/nevirapine were associated with higher susceptibility to HIVDR. The common mutations were M184V (17.38%) and K103N (22.14%). Additionally, the prevalence of M184V, S68G, M41L and G190A were different between the Han and Zhuang populations. Factors including age, gender, ethnicity, education level, occupation, infectious route, clinical stage, viral load, subtype, ART regimen and HIVDR showed significant associations with mortality.
    The factors contributing to drug resistance in the HIV-1 ART individuals in Guangxi appear to be notably intricate. Continuous reinforcement of drug resistance surveillance is imperative, accompanied by the optimization of ART regimens to mitigate virological failures effectively.
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  • 文章类型: Journal Article
    背景HIV-1CRF08_BC是昆明异性恋(HET)和静脉吸毒者(IDUs)中最普遍的流行亚型,云南。利用来自分子流行病学调查的基因序列的pol区域,我们开发了一个分子传输网络来分析其流行病学特征,评估其流行病学趋势,确定其潜在的传播关系,制定有针对性的干预措施。方法使用HyPhy2.2.4计算序列之间的成对遗传距离;使用GraphPad-Prism8.0确定标准遗传距离;应用细胞镜3.7.2对网络进行可视化。使用网络分析工具调查网络特征,使用MCODE工具观察网络的增长。我们使用逻辑回归模型来检查影响聚类的因素,并使用零膨胀泊松模型来研究影响潜在传输链接的因素。结果在0.008的标准遗传距离阈值下,858名研究参与者中有406人聚集在132个传播网络中,总网络链接为868个,每个序列的链接数在1到19之间。MCODE分析确定了网络中的三个重要的模块化集群,网络分数从4.9到7。在逻辑回归模型中,HET,中老年人,昆明北部和东南部的居民更容易进入传输网络(均P<0.05)。根据零膨胀泊松模型,年龄,变速器类别,采样年,婚姻状况,CD4+T水平对链接的大小有显著影响(均P<0.05)。结论昆明分子传输网络中的分子簇具有一定的特异性和聚集性。HIV-1分子网络分析提供了有关局部传播特征的信息,这些发现有助于确定减少传播干预措施的优先级。
    HIV-1CRF08_BC is the most prevalent epidemic subtype among heterosexual (HET) and intravenous drug users (IDUs) in Kunming, Yunnan. Using the pol region of gene sequences derived from molecular epidemiological surveys, we developed a molecular transmission network for the purpose of analyzing its epidemiological characteristics, assessing its epidemiological trends, identifying its potential transmission relationships, and developing targeted interventions. HyPhy 2.2.4 was used to calculate pairwise genetic distances between sequences; GraphPad-Prism 8.0 was employed to determine the standard genetic distance; and Cytoscope 3.7.2 was applied to visualize the network. We used the network analysis tools to investigate network characteristics and the Molecular Complex Detection (MCODE) tool to observe the growth of the network. We utilized a logistic regression model to examine the factors influencing clustering and a zero-inflated Poisson model to investigate the factors influencing potential transmission links. At the standard genetic distance threshold of 0.008, 406 out of 858 study participants were clustered in 132 dissemination networks with a total network linkage of 868, and the number of links per sequence ranged from 1 to 19. The MCODE analysis identified three significant modular clusters in the networks, with network scores ranging from 4.9 to 7. In models of logistic regression, HET, middle-aged and elderly individuals, and residents of northern and southeastern Kunming were more likely to enter the transmission network. According to the zero-inflated Poisson model, age, transmission category, sampling year, marital status, and CD4+ T level had a significant effect on the size of links. The molecular clusters in Kunming\'s molecular transmission network are specific and aggregate to a certain extent. HIV-1 molecular network analysis provided information on local transmission characteristics, and these findings helped to determine the priority of transmission-reduction interventions.
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  • 文章类型: Journal Article
    Strains of the HIV-1 circulating recombinant forms (CRFs) 06_cpx and 56_cpx were identified for the first time in Guangzhou, China. The nearly full-length genome (NFLG) sequence was amplified, and the PCR products were sequenced by the Sanger method. The CRF06_cpx and CRF56_cpx strains were identified using the Basic Local Alignment Search Tool (BLAST) and confirmed by neighbour-joining (NJ) phylogenetic analysis. Additionally, these strains were found to contain transmitted drug resistance mutations that have little effect on first-line efavirenz (EFV)-based treatment. Genetic analysis of the detailed sequence data will provide more information on the HIV-1 epidemic in China.
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  • 文章类型: Journal Article
    HIV-1CRF08_BC已成为中国南方异性恋者和静脉吸毒者(IDUs)的主要流行病。为了评估其流行趋势并促进有针对性的艾滋病毒预防,我们基于其pol序列构建了遗传传播网络,来自全国艾滋病毒分子流行病学调查。通过回顾性网络分析,研究流行病学和人口统计学与传播网络的相关性。在1,829个研究对象中,639个(34.9%)聚集在151个传输网络中。与集群增加相关的因素包括IDU,异性恋男人,年轻人和受教育程度较低的人(均P<0.05)。IDUs,MSM,年轻人和低文化程度的人也有更多的潜在传播联系(全部P<0.05)。异性恋女性和注射吸毒者之间的交叉联系最多,30.9%的异性恋女性与注射毒品使用者有关。异性恋女性的交叉联系主要是中年和单身女性(P<0.001)。这项研究表明,中国的HIV-1CRF08_BC流行仍在继续,超过三分之一的感染者聚集在传播网络中。同时,该研究可以帮助确定当地社区中活跃的CRF08_BC传播者,并通过有针对性的干预措施极大地促进了艾滋病的预防。
    HIV-1 CRF08_BC has become a major epidemic in heterosexuals and intravenous drug users (IDUs) in southern China. In order to evaluate the trends of its epidemic and facilitate targeted HIV prevention, we constructed the genetic transmission networks based on its pol sequences, derived from the National HIV Molecular Epidemiology Survey. Through retrospective network analysis, to study the epidemiological and demographic correlations with the transmission network. Of the 1,829 study subjects, 639 (34.9%) were clustered in 151 transmission networks. Factors associated with increased clustering include IDUs, heterosexual men, young adults and people with lower education (P < 0.05 for all). The IDUs, MSM, young adult and person with low education had more potential transmission links as well (P < 0.05 for all). The most crossover links were found between heterosexual women and IDUs, with 30.9% heterosexual women linked to IDUs. The crossover links heterosexual women were mainly those with middle age and single (P < 0.001). This study indicated that the HIV-1 CRF08_BC epidemic was still on going in China with more than one third of the infected people clustered in the transmission networks. Meanwhile, the study could help identify the active CRF08_BC spreader in the local community and greatly facilitate précising AIDS prevention with targeted intervention.
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  • 文章类型: Journal Article
    背景:抗逆转录病毒疗法(ART)的广泛使用导致了传播耐药性(TDR)的发展,这降低了ART功效。我们探讨了广西新诊断人群中TDR的患病率及其相关危险因素。
    方法:我们招募了1324名新诊断为HIV-1且未在广西自愿咨询和检测中心(VCT)接受ART的参与者,中国,他们没有接受艺术。系统发育关系,传输群集,使用HIV-1pol序列进行基因型耐药性分析。我们分析了人口统计学和病毒学因素与TDR的关系。
    结果:总计,1151个序列测序成功,其中83例(7.21%)显示TDR证据。多因素logistic回归分析显示,TDR患病率与未婚状态之间存在显着差异(校正比值比(aOR)=2.41,95%CI:1.23-4.71)。和CRF08_BC亚型(aOR=2.03,95%CI:1.13-3.64)。大多数TDR病例与非核苷逆转录酶抑制剂耐药有关(4.87%),V179E是检测到的最常见突变。我们确定了总共119个HIV传播簇(n=585,50.8%),其中18个(15.1%)集群显示TDR证据(36,41.86%)。确定了三个簇,其中包括彼此具有传播关系的耐药个体。以下参数与TDR传播风险相关:未婚状态,初中以下文化程度,和CRF08_BC亚型可能存在传输TDR的风险。
    结论:我们的研究结果表明TDR患病率适中,并强调了持续TDR监测和TDR缓解策略设计的重要性。
    BACKGROUND: The widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi.
    METHODS: We enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR.
    RESULTS: In total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23-4.71), and CRF08_BC subtype (aOR = 2.03, 95% CI: 1.13-3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08_BC subtype may be a risk of the transmission of TDR.
    CONCLUSIONS: Our findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.
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  • 文章类型: Journal Article
    The prevalence of HIV-1 in Guangxi is very high, and the rate of HIV-1 infection among men who have sex with men (MSM) has been increasing. Therefore, it is necessary to explore the patterns and risk factors of HIV transmission in Guangxi. For this purpose, individuals diagnosed with HIV-1 during 2013-2018 in Guangxi were recruited. Phylogenetic relationship, transmission clusters, and genotypic drug resistance analyses were performed based on HIV-1 pol sequences. Related factors were analysed to assess for their association with HIV-1 transmission. CRF07_BC (50.4%) and CRF01_AE (33.4%) were found to be the predominant subtypes. The analysed 1633 sequences (50.15%, Guangxi; 49.85%, other provinces) were segregated into 80 clusters (size per cluster, 2-704). We found that 75.3% of the individuals were in three clusters (size ˃ 100), and 73.8% were high-risk spreaders (links ≥ 4). Infection time, marital status, and subtype were significantly associated with HIV-1 transmission. Additionally, 80.2% of recent infections were linked to long-term infections, and 46.2% were linked to other provinces. A low level of transmitted drug resistance was detected (4.8%). Our findings indicated superclusters and high-risk HIV-1 spreaders among the MSM in Guangxi. Effective strategies blocking the route of transmission should be developed.
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