Pub Date : 2024-10-28DOI: 10.1016/j.humgen.2024.201353
Tariq Rahim , Summan Aslam , Aamir Sohail , Muhammad Jawad Khan
Bladder cancer is the tenth most common type of cancer worldwide. The lack of better diagnostic methods and effective treatments make it highly lethal. However, miRNAs are emerging as critical elements in diagnosing various diseases, especially cancers. Therefore, in the pursuit of improved diagnostic tools, this review aims to assess miRNAs interacting with their target genes in bladder cancer and evaluate the most significant miRNAs based on their molecular roles. After analyzing the literature and using several in-silico tools (e.g., miRWalk, miRDB, miRTarBase, TargetScan), we found that three miRNAs (miR-152-3p, miR-296-5p, miR-185-5p) out of a total of 1468 miRNAs were highly associated with bladder cancer, targeting three important genes: FGFR3, PTEN and PMF1. These three miRNAs may potentially serve as a panel for the diagnosis of bladder cancer after validation through extensive in-vitro and in-vivo studies. Moreover, these miRNAs could also be considered for therapeutic intervention against bladder cancer, following proper validation through in vivo studies.
{"title":"Molecular role of miR-152-3p, miR-296-5p and miR-185-5p in urinary bladder cancer etiology","authors":"Tariq Rahim , Summan Aslam , Aamir Sohail , Muhammad Jawad Khan","doi":"10.1016/j.humgen.2024.201353","DOIUrl":"10.1016/j.humgen.2024.201353","url":null,"abstract":"<div><div>Bladder cancer is the tenth most common type of cancer worldwide. The lack of better diagnostic methods and effective treatments make it highly lethal. However, miRNAs are emerging as critical elements in diagnosing various diseases, especially cancers. Therefore, in the pursuit of improved diagnostic tools, this review aims to assess miRNAs interacting with their target genes in bladder cancer and evaluate the most significant miRNAs based on their molecular roles. After analyzing the literature and using several <em>in-silico</em> tools (<em>e.g.</em>, miRWalk, miRDB, miRTarBase, TargetScan), we found that three miRNAs (miR-152-3p, miR-296-5p, miR-185-5p) out of a total of 1468 miRNAs were highly associated with bladder cancer, targeting three important genes: <em>FGFR3</em>, <em>PTEN</em> and <em>PMF1</em>. These three miRNAs may potentially serve as a panel for the diagnosis of bladder cancer after validation through extensive <em>in-vitro</em> and <em>in-vivo</em> studies. Moreover, these miRNAs could also be considered for therapeutic intervention against bladder cancer, following proper validation through <em>in vivo</em> studies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201353"},"PeriodicalIF":0.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.humgen.2024.201352
Hala M. Raslan , Hanan Abd Elmawgoud Atia , Sherein Saeid Elshaer , Shaimaa M. Sabry , Yasmin Mosaad Mohammed , Khalda S. Amr
Background
MicroRNAs (miRNAs) are involved in the pathogenesis of rheumatoid arthritis (RA) through modulating gene expression.
Aim
To assess the plasma expression of miR-16, miR-132, miR-146 and miR-223 in patients with RA and their relation to activity and severity of the disease and their potential value as biomarkers. Through bioinformatics study we aimed to determine the predictor target genes of the studied miRNAs to clarify their role in RA pathogenesis.
Methods
The study comprised 73 patients suffering from RA and 50 healthy individuals. We used the disease activity score-28 (DAS-28) to assess disease activity. Joint damage was assessed by Kaarela and Kautiainen modification of Larsen scale. Anti-anticyclic citrullinated peptide (anti-CCP) antibodies, serum high sensitive C reactive protein (hsCRP) and rheumatoid factor (RF) were assayed by ELISA. Plasma miR-223, miR-146a, miR-16 and miR-132 were quantified by qRT-PCR followed by a simple dry laboratory analysis of the involved target genes of the studied miRNAs in RA pathogenesis by KEGG pathways.
Results
In comparison to controls, RA patients showed overexpressed miR-146a, miR-223and miR-16, while miR-132 was down-regulated. Additionally, miR-146a correlated positively with DAS28, anti-CCP antibodies and RF. Bioinformatics revealed that the predicted targeted genes of miR-146a, miR-16, miR-223 and miR-132 are potential contributing factors for RA pathogenesis and bone degradation.
Conclusion
miR-146a, miR-223, miR-16 and miR-132 may be potential non-invasive molecular biomarkers for RA diagnosis. Plasma miR-146a might be considered as potential biomarker for disease activity. The predicted genes targeted by miR-146a, miR-223, miR-16 and miR-132 are implicated in RA pathogenesis and ultimately can be used in future target therapeutic approach.
目的 评估 RA 患者血浆中 miR-16、miR-132、miR-146 和 miR-223 的表达及其与疾病活动和严重程度的关系，以及它们作为生物标记物的潜在价值。通过生物信息学研究，我们旨在确定所研究的 miRNA 的预测靶基因，以明确它们在 RA 发病机制中的作用。我们使用疾病活动度评分-28（DAS-28）来评估疾病活动度。关节损伤采用Kaarela和Kautiainen修改的Larsen量表进行评估。抗环瓜氨酸肽（anticyclic citrullinated peptide，anti-CCP）抗体、血清高敏C反应蛋白（hsCRP）和类风湿因子（rheumatoid factor，RF）通过酶联免疫吸附试验（ELISA）进行检测。结果与对照组相比，RA 患者的 miR-146a、miR-223 和 miR-16 表达过高，而 miR-132 则下调。此外，miR-146a与DAS28、抗CCP抗体和RF呈正相关。结论miR-146a、miR-223、miR-16和miR-132可能是诊断RA的潜在非侵入性分子生物标志物。血浆 miR-146a 可被视为疾病活动性的潜在生物标志物。miR-146a、miR-223、miR-16 和 miR-132 预测的靶基因与 RA 发病机制有关，最终可用于未来的靶向治疗方法。
{"title":"Plasma expression and bioinformatic analysis of Mir-16, Mir-132, Mir-146 and Mir-223 in patients with rheumatoid arthritis","authors":"Hala M. Raslan , Hanan Abd Elmawgoud Atia , Sherein Saeid Elshaer , Shaimaa M. Sabry , Yasmin Mosaad Mohammed , Khalda S. Amr","doi":"10.1016/j.humgen.2024.201352","DOIUrl":"10.1016/j.humgen.2024.201352","url":null,"abstract":"<div><h3>Background</h3><div>MicroRNAs (miRNAs) are involved in the pathogenesis of rheumatoid arthritis (RA) through modulating gene expression.</div></div><div><h3>Aim</h3><div>To assess the plasma expression of miR-16, miR-132, miR-146 and miR-223 in patients with RA and their relation to activity and severity of the disease and their potential value as biomarkers. Through bioinformatics study we aimed to determine the predictor target genes of the studied miRNAs to clarify their role in RA pathogenesis.</div></div><div><h3>Methods</h3><div>The study comprised 73 patients suffering from RA and 50 healthy individuals. We used the disease activity score-28 (DAS-28) to assess disease activity. Joint damage was assessed by Kaarela and Kautiainen modification of Larsen scale. Anti-anticyclic citrullinated peptide (anti-CCP) antibodies, serum high sensitive C reactive protein (hsCRP) and rheumatoid factor (RF) were assayed by ELISA. Plasma miR-223, miR-146a, miR-16 and miR-132 were quantified by qRT-PCR followed by a simple dry laboratory analysis of the involved target genes of the studied miRNAs in RA pathogenesis by KEGG pathways.</div></div><div><h3>Results</h3><div>In comparison to controls, RA patients showed overexpressed miR-146a, miR-223and miR-16, while miR-132 was down-regulated. Additionally, miR-146a correlated positively with DAS28, anti-CCP antibodies and RF. Bioinformatics revealed that the predicted targeted genes of miR-146a, miR-16, miR-223 and miR-132 are potential contributing factors for RA pathogenesis and bone degradation.</div></div><div><h3>Conclusion</h3><div>miR-146a, miR-223, miR-16 and miR-132 may be potential non-invasive molecular biomarkers for RA diagnosis. Plasma miR-146a might be considered as potential biomarker for disease activity. The predicted genes targeted by miR-146a, miR-223, miR-16 and miR-132 are implicated in RA pathogenesis and ultimately can be used in future target therapeutic approach.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201352"},"PeriodicalIF":0.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Migraine disorder is a complicated condition for which a large number of genetic variants determine susceptibility. The 5-HTTLPR of the SLC6A4 gene is one of these genetic variations, and it is hypothesized that it plays a role in defining the susceptibility to the disease.
Aim
Therefore, through the utilization of the meta-analysis methodology, the current investigation aimed to determine whether or not there is an association between the 5-HTTLPR and the likelihood of developing migraines.
Method
The present study utilizes the PRISMA guideline to review existing literature from the electronic database to perform pooled analysis, and also includes quality assessment, association analysis, publication bias, and heterogeneity analysis using the NOS tool, OR with 95 % CI, tests of Begg's with Egger's test, and χ2 based on Cochran's Q Test with I2 tests respectively.
Result
Using a systematic literature review, we found 14 studies representing 2972 participants, with 1276 cases diagnosed with migraine and 1696 serving as controls. It was observed that after utilizing multiple genetic models only allele (1.14 [1.01–1.29], p-value = 0.025) and recessive model (1.24 [1.01–152], p-value = 0.03), in contrast to other genetic models were found to be significantly associated with overall migraine but not with MA and MWA.
Discussion & conclusion
In conclusion, according to the allele and recessive model, the current investigation revealed a statistically significant relationship between 5-HTTLPR and the likelihood of developing migraines.
{"title":"Impact of 5-HTTLPR of SLC6A4 on migraine susceptibility: A meta-analysis with trial sequential analysis","authors":"Amrit Sudershan , Hardeep Kumar , Sandeepa Bailam , Rakesh K. Panjaliya , Parvinder Kumar","doi":"10.1016/j.humgen.2024.201347","DOIUrl":"10.1016/j.humgen.2024.201347","url":null,"abstract":"<div><h3>Background</h3><div>Migraine disorder is a complicated condition for which a large number of genetic variants determine susceptibility. The 5-HTTLPR of the <em>SLC6A4</em> gene is one of these genetic variations, and it is hypothesized that it plays a role in defining the susceptibility to the disease.</div></div><div><h3>Aim</h3><div>Therefore, through the utilization of the meta-analysis methodology, the current investigation aimed to determine whether or not there is an association between the 5-HTTLPR and the likelihood of developing migraines.</div></div><div><h3>Method</h3><div>The present study utilizes the PRISMA guideline to review existing literature from the electronic database to perform pooled analysis, and also includes quality assessment, association analysis, publication bias, and heterogeneity analysis using the NOS tool, OR with 95 % CI, tests of Begg's with Egger's test, and χ2 based on Cochran's Q Test with I<sup>2</sup> tests respectively.</div></div><div><h3>Result</h3><div>Using a systematic literature review, we found 14 studies representing 2972 participants, with 1276 cases diagnosed with migraine and 1696 serving as controls. It was observed that after utilizing multiple genetic models only allele (1.14 [1.01–1.29], <em>p</em>-value = 0.025) and recessive model (1.24 [1.01–152], p-value = 0.03), in contrast to other genetic models were found to be significantly associated with overall migraine but not with MA and MWA.</div></div><div><h3>Discussion & conclusion</h3><div>In conclusion, according to the allele and recessive model, the current investigation revealed a statistically significant relationship between 5-HTTLPR and the likelihood of developing migraines.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201347"},"PeriodicalIF":0.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1016/j.humgen.2024.201349
Marwa Mohammed Ibrahim Mohammed Khalil , Randa Mohamed Seddik , Manal Monir Mansour , Hany Abdelbary Abdelaziz Elbasuony , Sara A. El Derbaly
Background
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Long noncoding RNAs (lncRNAs) could contribute significantly to HCC development through diverse mechanisms, such as the recruitment of many regulatory protein complexes. This study aimed to evaluate the expression levels of the lncRNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 in liver cirrhosis and HCC and also assess their diagnostic performance as biomarkers for HCC.
Methods
In total, 180 participants were in this study, classified into three groups (60 participants in each): Group I (hepatocellular carcinoma patients), Group II (liver cirrhosis patients), and Group III (apparently healthy individuals). The expressions of the HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were detected using a reverse-transcriptase real-time polymerase chain reaction (qRT-PCR).
Results
The expression levels of HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were markedly increased in the HCC patients compared with those in the cirrhotic patients and controls. They also exhibited greater sensitivity as diagnostic biomarkers than alpha-fetoprotein.
Conclusions
The HOTAIR, HOST2, HOXA-AS2, and MALAT1 lncRNAs exhibit promising potential as valuable diagnostic biomarkers of HCC and in differentiating HCC from liver cirrhosis. Furthermore, combining alpha-fetoprotein can yield higher accuracy.
{"title":"Detection and validity of long non-coding RNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 as biomarkers for hepatocellular carcinoma","authors":"Marwa Mohammed Ibrahim Mohammed Khalil , Randa Mohamed Seddik , Manal Monir Mansour , Hany Abdelbary Abdelaziz Elbasuony , Sara A. El Derbaly","doi":"10.1016/j.humgen.2024.201349","DOIUrl":"10.1016/j.humgen.2024.201349","url":null,"abstract":"<div><h3>Background</h3><div>Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Long noncoding RNAs (lncRNAs) could contribute significantly to HCC development through diverse mechanisms, such as the recruitment of many regulatory protein complexes. This study aimed to evaluate the expression levels of the lncRNAs HOST2, HOTAIR, HOXA-AS2, and MALAT1 in liver cirrhosis and HCC and also assess their diagnostic performance as biomarkers for HCC.</div></div><div><h3>Methods</h3><div>In total, 180 participants were in this study, classified into three groups (60 participants in each): Group I (hepatocellular carcinoma patients), Group II (liver cirrhosis patients), and Group III (apparently healthy individuals). The expressions of the HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were detected using a reverse-transcriptase real-time polymerase chain reaction (qRT-PCR).</div></div><div><h3>Results</h3><div>The expression levels of HOST2, HOTAIR, HOXA-AS2, and MALAT1 lncRNAs were markedly increased in the HCC patients compared with those in the cirrhotic patients and controls. They also exhibited greater sensitivity as diagnostic biomarkers than alpha-fetoprotein.</div></div><div><h3>Conclusions</h3><div>The HOTAIR, HOST2, HOXA-AS2, and MALAT1 lncRNAs exhibit promising potential as valuable diagnostic biomarkers of HCC and in differentiating HCC from liver cirrhosis. Furthermore, combining alpha-fetoprotein can yield higher accuracy.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201349"},"PeriodicalIF":0.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-20DOI: 10.1016/j.humgen.2024.201350
Xiao Xu , Xinju Zhang , Xuan Deng , Fuzhi Sheng , Guojun Cao , Deliang Fu , Ming Guan
Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.
{"title":"Quantitative detection of miR-25 for early diagnosis, postoperative assessment and TNM staging of pancreatic cancer","authors":"Xiao Xu , Xinju Zhang , Xuan Deng , Fuzhi Sheng , Guojun Cao , Deliang Fu , Ming Guan","doi":"10.1016/j.humgen.2024.201350","DOIUrl":"10.1016/j.humgen.2024.201350","url":null,"abstract":"<div><div>Objectives: Pancreatic cancer is one of the most common malignant tumors of the digestive tract. Due to its strong concealment and rapid disease progress, it is characterized by high mortality and low cure rate. Current research focuses on screening high-risk populations, preventing the occurrence of pancreatic cancer and developing imaging technology and tumor markers for early diagnosis. This study aimed to investigate the absolute quantitative detection of microRNA-25 (miR-25) and reveal its quantitative changes in the treatment of pancreatic cancer. We compared serum miR-25 level between pancreatic cancer patients and other tumor patients, especially those with gastrointestinal cancer, to provide further evidence for early diagnosis, differential diagnosis and prognosis of pancreatic cancer. Methods: We collected serum samples from 51 pancreatic cancer patients (including 21 patients with preoperative and postoperative samples), 52 pancreatitis patients, 141 other tumor patients, and 50 healthy individuals from Huashan Hospital, Fudan University. The serum levels of miR-25, Carbohydrate Antigen 19–9 (CA19–9), Carbohydrate Antigen 125 (CA125) and Carcinoembryonic Antigen (CEA) in these populations were measured to analyze the value of miR-25 quantitative detection in the diagnosis, postoperative assessment and Tumor Node Metastasis (TNM) staging of pancreatic cancer. Results: Among the 51 pancreatic cancer patients, 50 cases (98.04 %) showed miR-25 levels above the threshold (3333 copies/μl), while all samples in normal group showed negative. The mean level of miR-25 in serum was 5707.45 ± 361.02 copies/μl. In other tumor groups, 21/141 (14.89 %) patients showed positive results and the mean miR-25 level was 847.09 ± 125.97 copies/μl. Comparing before and after operation in 21 paired samples, the level of miR-25 declined significantly after operation, with an average decline rate of 86.36 %. Conclusions: Serum miR-25 levels were significantly higher in pancreatic cancer patients compared to both normal and other tumor groups and decreased significantly after surgery. In addition, miR-25 showed higher sensitivity than common tumor markers (CA19–9, CA125, CEA) in early diagnosis of pancreatic cancer, and proved to be of significant value in evaluating the effect of surgical treatment.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201350"},"PeriodicalIF":0.5,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<div><h3>Background</h3><div>Short Tandem Repeats (STRs) are pivotal to efficient human DNA profiling. Including mini-STRs can further improve the assay's efficiency. The FBI's (Federal Bureau of Investigation) expanded Combined DNA Index System (CODIS) list contains twenty STRs for human identification. The NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which include markers from the expanded CODIS list, are National DNA Index System (NDIS) recommended markers, and comply with the NDIS recommended allelic range. In addition, the kit also includes 8 more markers including Penta D and Penta E. The NeoTyper Autosomal kit STR markers includes 14 mini-STR which makes it very effective for the human identification of the degraded samples like unidentified body remains.</div><div>This is a developmental validation study for NeoTyper, based on the listed Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines.</div></div><div><h3>Methodology</h3><div>We extracted the human genomic DNA from blood and FFPE (Formalin-Fixed Paraffin-Embedded) samples, and performed PCR amplification for the 28 loci using the developed kit, NeoTyper, which features a six-dye chemistry. The amplified products were run on 3500xL Genetic Analyzer. We used GeneMapper ID-X v.1.4 (Applied Biosystems) to analyse peak height and allele calling. Developmental validation parameters, including genetic characterization, analysis of sensitivity, female-male mixture, precision, and accuracy (repeatability and reproducibility), were investigated and analysed. Furthermore, intra- and inter-laboratory comparisons, as well as mini-STR analysis and validation were done.</div></div><div><h3>Results</h3><div>The developed NeoTyper Autosomal kit demonstrated 100 % sensitivity up to a DNA concentration of 62.5 pg, as measured by the number of alleles called. The assay also demonstrated good precision (measured in terms of standard deviation, SD ranging between 0.60 and 0.77) and reproducibility, with alleles called at 100 % accuracy. Furthermore, precision was high (measured as SD ranging from 0.50 to 0.66), with a 100 % accuracy. In 90.9 % of the samples (10 out of 11 female-male sample varied ratio), the mixture analysis revealed 100 % of the alleles being called. A comparative analysis of mini-STRs in GlobalFiler and NeoTyper Autosomal kit revealed a 100 % accuracy of the NeoTyper mini-STRs.</div></div><div><h3>Conclusion</h3><div>In conclusion, the NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which includes markers from expanded CODIS list; are NDIS accepted markers and comply with their recommended allelic range. The integration of mini-STRs in the kit demonstrates its efficacy and reliability, particularly when addressing the difficulties posed by degraded samples. This developmental validation study demonstrates consistent performance with high sensiti
{"title":"Developmental validation of NeoTyper autosomal STR kit","authors":"Sudhir Verma , Rajan Pal , Jagdish Kandpal , Ankit Singh Bhadauriya , Manas Pandey , Mitali Kushwaha , Shiv Mohan Singh , Supriya Singh","doi":"10.1016/j.humgen.2024.201348","DOIUrl":"10.1016/j.humgen.2024.201348","url":null,"abstract":"<div><h3>Background</h3><div>Short Tandem Repeats (STRs) are pivotal to efficient human DNA profiling. Including mini-STRs can further improve the assay's efficiency. The FBI's (Federal Bureau of Investigation) expanded Combined DNA Index System (CODIS) list contains twenty STRs for human identification. The NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which include markers from the expanded CODIS list, are National DNA Index System (NDIS) recommended markers, and comply with the NDIS recommended allelic range. In addition, the kit also includes 8 more markers including Penta D and Penta E. The NeoTyper Autosomal kit STR markers includes 14 mini-STR which makes it very effective for the human identification of the degraded samples like unidentified body remains.</div><div>This is a developmental validation study for NeoTyper, based on the listed Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines.</div></div><div><h3>Methodology</h3><div>We extracted the human genomic DNA from blood and FFPE (Formalin-Fixed Paraffin-Embedded) samples, and performed PCR amplification for the 28 loci using the developed kit, NeoTyper, which features a six-dye chemistry. The amplified products were run on 3500xL Genetic Analyzer. We used GeneMapper ID-X v.1.4 (Applied Biosystems) to analyse peak height and allele calling. Developmental validation parameters, including genetic characterization, analysis of sensitivity, female-male mixture, precision, and accuracy (repeatability and reproducibility), were investigated and analysed. Furthermore, intra- and inter-laboratory comparisons, as well as mini-STR analysis and validation were done.</div></div><div><h3>Results</h3><div>The developed NeoTyper Autosomal kit demonstrated 100 % sensitivity up to a DNA concentration of 62.5 pg, as measured by the number of alleles called. The assay also demonstrated good precision (measured in terms of standard deviation, SD ranging between 0.60 and 0.77) and reproducibility, with alleles called at 100 % accuracy. Furthermore, precision was high (measured as SD ranging from 0.50 to 0.66), with a 100 % accuracy. In 90.9 % of the samples (10 out of 11 female-male sample varied ratio), the mixture analysis revealed 100 % of the alleles being called. A comparative analysis of mini-STRs in GlobalFiler and NeoTyper Autosomal kit revealed a 100 % accuracy of the NeoTyper mini-STRs.</div></div><div><h3>Conclusion</h3><div>In conclusion, the NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which includes markers from expanded CODIS list; are NDIS accepted markers and comply with their recommended allelic range. The integration of mini-STRs in the kit demonstrates its efficacy and reliability, particularly when addressing the difficulties posed by degraded samples. This developmental validation study demonstrates consistent performance with high sensiti","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201348"},"PeriodicalIF":0.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-15DOI: 10.1016/j.humgen.2024.201345
G.B. Priyadharshini, C. Jaynthy
Parkinson's disease (PD) is characterised by developing postural instability, resting seizures, tremors, and a movement problem coupled with stiffness. All the available drugs can improve motor function considerably, but they can also have negative side effects, especially if the problem gets worse. The structure-activity relation was performed in the DISCOVERY STUDIO V2.5.5 pharmacophore model using the HypoGen algorithm for a training set of 15 compounds. Here, xenin peptide fits well with a least cost difference and a fit value of 10.46, indicating a favourable pharmacological characteristic. Therefore, we tried applying gene network analysis in cytoHubba to find the hub gene for PD in Danio rerio and Homo sapiens, as zebrafish and humans share many disease proteins and processes. Molecular docking studies for the hub gene polyubiquitin B from Danio rerio and Parkin from Homo sapiens, as well as the peptide xenin obtained from the marine sponge extract MS01 was performed. The peptide exhibits a substantial binding affinity with the receptor UBB through 8 and PRKN through 4 intermolecular hydrogen bonds in their bonded and non-bonded interactions, although it has little effect on the protein structure, according to simulation studies and dynamical free energy calculations. The protein structure has also been stabilised in terms of energy, secondary structure, and flexibility by the peptide binding. In addition to in-silico analysis the extract was tested in-vitro on SH-SY5Y cells for its effectiveness against ROS and cell viability, which proved its qualitative effect.
{"title":"Unravelling the protective effects of peptide isolated from marine sponge extract MS01 against SH-SY5Y cell line and its in-silico pharmacokinetic analysis","authors":"G.B. Priyadharshini, C. Jaynthy","doi":"10.1016/j.humgen.2024.201345","DOIUrl":"10.1016/j.humgen.2024.201345","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterised by developing postural instability, resting seizures, tremors, and a movement problem coupled with stiffness. All the available drugs can improve motor function considerably, but they can also have negative side effects, especially if the problem gets worse. The structure-activity relation was performed in the DISCOVERY STUDIO V2.5.5 pharmacophore model using the HypoGen algorithm for a training set of 15 compounds. Here, xenin peptide fits well with a least cost difference and a fit value of 10.46, indicating a favourable pharmacological characteristic. Therefore, we tried applying gene network analysis in cytoHubba to find the hub gene for PD in <em>Danio rerio</em> and <em>Homo sapiens</em>, as zebrafish and humans share many disease proteins and processes. Molecular docking studies for the hub gene polyubiquitin B from <em>Danio rerio</em> and Parkin from <em>Homo sapiens</em>, as well as the peptide xenin obtained from the marine sponge extract MS01 was performed. The peptide exhibits a substantial binding affinity with the receptor UBB through 8 and PRKN through 4 intermolecular hydrogen bonds in their bonded and non-bonded interactions, although it has little effect on the protein structure, according to simulation studies and dynamical free energy calculations. The protein structure has also been stabilised in terms of energy, secondary structure, and flexibility by the peptide binding. In addition to in-silico analysis the extract was tested in-vitro on SH-SY5Y cells for its effectiveness against ROS and cell viability, which proved its qualitative effect.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201345"},"PeriodicalIF":0.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MicroRNAs (MiRNAs) are master regulators of gene expression and have been suggested as potential diagnostic and therapeutic biomarkers in variety of complex diseases. Venous thromboembolism is a major cause of morbidity and mortality worldwide. Several miRNA expression studies have been conducted to identify miRNAs linked to VTE prognosis. These studies reveal that various miRNAs are significantly up-regulated and down-regulated in VTE patients in comparison to healthy controls. Present meta-analysis deliberate findings of such studies to identify most potential miRNA targets associated with VTE.
Methodology
Comprehensive literature review on Pubmed was conducted. Present analysis assessed 20 research article out of a total of 383 articles screened, based on inclusion and exclusion criteria. The up-regulated and down-regulated miRNAs obtained from selected research articles were subjected to meta-analysis. The differentially expressed miRNAs so obtained and were used for further bioinformatic analysis, including gene ontology and pathway analysis of their target genes, to study their potential involvement in VTE pathogenesis.
Results
Twenty articles selected for meta-analysis included a total of 808 patients. These included 26 up-regulated miRNAs and 11 down-regulated miRNAs. The meta-analysis based on Odds ratio suggested that one up-regulated miRNA (hsa-miR-1233-3p) and two down-regulated miRNAs (hsa-miR-103a-3p and hsa-miR-200c) returned significantly higher Odds compared to other miRNAs. Further bioinformatics analysis of their target genes revealed that these miRNAs target a large number of genes involved in cell adhesion, cell migration, endothelial activation and inflammation genes.
Conclusions
Three miRNAs, viz.; hsa-miR-1233-3p, hsa-miR-103a-3p and hsa-miR-200c may play a crucial role in VTE pathogenesis and has potential to serve as reliable diagnostic or therapeutic biomarkers for VTE.
{"title":"Identification of potential microRNAs involved in pathogenesis of venous thromboembolism (VTE): A meta analysis","authors":"Sunanda Arya, Rashi Khare, Iti Garg, Swati Srivastava","doi":"10.1016/j.humgen.2024.201346","DOIUrl":"10.1016/j.humgen.2024.201346","url":null,"abstract":"<div><h3>Objective</h3><div>MicroRNAs (MiRNAs) are master regulators of gene expression and have been suggested as potential diagnostic and therapeutic biomarkers in variety of complex diseases. Venous thromboembolism is a major cause of morbidity and mortality worldwide. Several miRNA expression studies have been conducted to identify miRNAs linked to VTE prognosis. These studies reveal that various miRNAs are significantly up-regulated and down-regulated in VTE patients in comparison to healthy controls. Present meta-analysis deliberate findings of such studies to identify most potential miRNA targets associated with VTE.</div></div><div><h3>Methodology</h3><div>Comprehensive literature review on Pubmed was conducted. Present analysis assessed 20 research article out of a total of 383 articles screened, based on inclusion and exclusion criteria. The up-regulated and down-regulated miRNAs obtained from selected research articles were subjected to meta-analysis. The differentially expressed miRNAs so obtained and were used for further bioinformatic analysis, including gene ontology and pathway analysis of their target genes, to study their potential involvement in VTE pathogenesis.</div></div><div><h3>Results</h3><div>Twenty articles selected for meta-analysis included a total of 808 patients. These included 26 up-regulated miRNAs and 11 down-regulated miRNAs. The meta-analysis based on Odds ratio suggested that one up-regulated miRNA (hsa-miR-1233-3p) and two down-regulated miRNAs (hsa-miR-103a-3p and hsa-miR-200c) returned significantly higher Odds compared to other miRNAs. Further bioinformatics analysis of their target genes revealed that these miRNAs target a large number of genes involved in cell adhesion, cell migration, endothelial activation and inflammation genes.</div></div><div><h3>Conclusions</h3><div>Three miRNAs, viz.; hsa-miR-1233-3p, hsa-miR-103a-3p and hsa-miR-200c may play a crucial role in VTE pathogenesis and has potential to serve as reliable diagnostic or therapeutic biomarkers for VTE.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201346"},"PeriodicalIF":0.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.humgen.2024.201343
Arvin Hassani, Saeid Ghorbian
Background
Breast cancer (BC) is one of the most frequent types of cancer and the second leading cause of cancer-affiliate death among ladies. BC is a heterogeneous sickness that is impacted by environment and genetic elements. Diagnosis in the early stages impacts treatment and patient survival rate. miRNA can play a vital role in BC's early stages of tumorigenesis. Single nucleotide polymorphism (SNP) can cause changes in miRNA expression and function, which are related to the risk of several cancers.
Aim
The goal of this examination is to assess the affiliation among two has-miR-605 (rs2043556A > G) and has-miR-618 (rs2682818 C > A) gene polymorphisms with the risk of BC in the Iranian ladies.
Methods
Our case-control examination assessed two hundred whole blood samples of one hundred ladies with BC and one hundred healthy ladies. Hence, to assess the connection between the presence of SNP miRNA genes and the risk of BC, genotyping was done by the usage of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, then the usage of the Chi-square test of SPSS software statistically analyzed the acquired result.
Results
Our findings confirmed a statistically substantial distinction within the genotype frequency of the has-miR-618 gene polymorphism among the groups (P = 0.043), whereas no statistically substantial distinction inside the genotype frequency of the has-miR-605 gene polymorphism among the control and case (P = 0.183). In addition, the allelic frequency of two polymorphisms, (rs2043556 A > G) G allele (OR = 2.163, CI 95 % = 1.56–2.988, P = 0.022) and (rs2682818 C > A) A allele (OR = 3.997, CI 95 % = 1.584–10.081, P = 0.002) substantially enhance the risk of BC.
Conclusion
The results show that the G allele of rs2043556 and the A allele of rs2682818 increase the risk of BC in the women population of East Azerbaijan province.
背景乳腺癌（BC）是最常见的癌症类型之一，也是女性死于癌症的第二大原因。乳腺癌是一种受环境和遗传因素影响的异质性疾病。miRNA 在 BC 肿瘤发生的早期阶段起着至关重要的作用。单核苷酸多态性（SNP）可导致 miRNA 表达和功能的改变，而 miRNA 表达和功能的改变与多种癌症的风险有关。方法我们的病例对照研究评估了 100 名 BC 患者和 100 名健康女性的 200 份全血样本。因此，为了评估 SNP miRNA 基因的存在与 BC 风险之间的联系，我们使用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）方法进行了基因分型，然后使用 SPSS 软件的卡方检验对所得结果进行了统计分析。结果我们的研究结果证实，组间 has-miR-618 基因多态性的基因型频率存在统计学意义上的显著差异（P = 0.043），而对照组和病例组间 has-miR-605 基因多态性的基因型频率没有统计学意义上的显著差异（P = 0.183）。此外，两个多态性的等位基因频率，（rs2043556 A > G）G 等位基因（OR = 2.163，CI 95 % = 1.56-2.988，P = 0.022）和（rs2682818 C > A）A 等位基因（OR = 3.997，CI 95 % = 1.584-10.081，P = 0.结果表明，rs2043556 的 G 等位基因和 rs2682818 的 A 等位基因会增加东阿塞拜疆省妇女患 BC 的风险。
{"title":"Validation of gene polymorphisms (rs2682818 and rs2043556) in has-miR-618 and has-miR-605 with the breast cancer susceptibility","authors":"Arvin Hassani, Saeid Ghorbian","doi":"10.1016/j.humgen.2024.201343","DOIUrl":"10.1016/j.humgen.2024.201343","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is one of the most frequent types of cancer and the second leading cause of cancer-affiliate death among ladies. BC is a heterogeneous sickness that is impacted by environment and genetic elements. Diagnosis in the early stages impacts treatment and patient survival rate. miRNA can play a vital role in BC's early stages of tumorigenesis. Single nucleotide polymorphism (SNP) can cause changes in miRNA expression and function, which are related to the risk of several cancers.</div></div><div><h3>Aim</h3><div>The goal of this examination is to assess the affiliation among two has-miR-605 (rs2043556A > G) and has-miR-618 (rs2682818 C > A) gene polymorphisms with the risk of BC in the Iranian ladies.</div></div><div><h3>Methods</h3><div>Our case-control examination assessed two hundred whole blood samples of one hundred ladies with BC and one hundred healthy ladies. Hence, to assess the connection between the presence of SNP miRNA genes and the risk of BC, genotyping was done by the usage of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, then the usage of the <em>Chi-square test</em> of SPSS software statistically analyzed the acquired result.</div></div><div><h3>Results</h3><div>Our findings confirmed a statistically substantial distinction within the genotype frequency of the has-miR-618 gene polymorphism among the groups (<em>P</em> = 0.043), whereas no statistically substantial distinction inside the genotype frequency of the has-miR-605 gene polymorphism among the control and case (<em>P</em> = 0.183). In addition, the allelic frequency of two polymorphisms, (rs2043556 A > G) G allele (OR = 2.163, CI 95 % = 1.56–2.988, <em>P</em> = 0.022) and (rs2682818 C > A) A allele (OR = 3.997, CI 95 % = 1.584–10.081, <em>P</em> = 0.002) substantially enhance the risk of BC.</div></div><div><h3>Conclusion</h3><div>The results show that the G allele of rs2043556 and the A allele of rs2682818 increase the risk of BC in the women population of East Azerbaijan province.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201343"},"PeriodicalIF":0.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1016/j.humgen.2024.201344
Ali H. Mahmood , Salwa J. Al-Awadi , Marwa M. Al-Attar , Rusul A.A. Alshammary , Riam Sabah Abood
Background
The angiotensin-converting enzyme 2 (ACE2) receptor plays a critical role in mediating SARS-CoV-2 infection. Understanding the genetic factors influencing COVID-19 severity is crucial for developing effective treatment strategies. This study aimed to investigate the association between genetic polymorphism of the ACE gene, specifically the insertion/deletion (I/D) polymorphism in the promoter region, and clinical parameters in COVID-19 patients.
Methods
A case-control study was conducted with 225 participants from an Iraqi population. Blood samples were collected for hematological analysis and ACE genotyping. The association between ACE genotypes (DD, ID, II), demographic factors, and clinical parameters, including D-dimer, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), white blood cell (WBC) count, lymphocyte count, packed cell volume (PCV), red blood cell (RBC) count, hemoglobin (HB), and platelet count, was assessed.
Results
COVID-19 patients exhibited significant differences compared to controls regarding D-dimer, ferritin, LDH, CRP, WBC, lymphocytes, PCV, and RBC (P < 0.05), while no significant differences were found for HB and platelet counts. The DD genotype was predominant (43.11 %), followed by ID (39.56 %) and II (17.33 %). Notably, a significant association was observed between D-dimer levels and ACE genotype (P < 0.0001), with higher levels observed in individuals with the DD genotype. Additionally, a significant correlation was found between ACE genotype and sex (P = 0.0163). No significant association was observed between genotype and ICU admission or lung CT severity.
Conclusion
Our findings suggest a potential link between the ACE D/D genotype and elevated D-dimer levels in COVID-19 patients, indicating a potential role for ACE gene polymorphism in influencing disease severity. Further research is warranted to elucidate the underlying mechanisms and explore the potential for personalized treatment approaches based on ACE genotype.
{"title":"Investigate the association between genetic polymorphisms of ACE and ACE-2 with some biomarkers in Iraqi patients with COVID-19.","authors":"Ali H. Mahmood , Salwa J. Al-Awadi , Marwa M. Al-Attar , Rusul A.A. Alshammary , Riam Sabah Abood","doi":"10.1016/j.humgen.2024.201344","DOIUrl":"10.1016/j.humgen.2024.201344","url":null,"abstract":"<div><h3>Background</h3><div>The angiotensin-converting enzyme 2 (ACE2) receptor plays a critical role in mediating SARS-CoV-2 infection. Understanding the genetic factors influencing COVID-19 severity is crucial for developing effective treatment strategies. This study aimed to investigate the association between genetic polymorphism of the <em>ACE</em> gene, specifically the insertion/deletion (I/D) polymorphism in the promoter region, and clinical parameters in COVID-19 patients.</div></div><div><h3>Methods</h3><div>A case-control study was conducted with 225 participants from an Iraqi population. Blood samples were collected for hematological analysis and <em>ACE</em> genotyping. The association between <em>ACE</em> genotypes (DD, ID, II), demographic factors, and clinical parameters, including D-dimer, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), white blood cell (WBC) count, lymphocyte count, packed cell volume (PCV), red blood cell (RBC) count, hemoglobin (HB), and platelet count, was assessed.</div></div><div><h3>Results</h3><div>COVID-19 patients exhibited significant differences compared to controls regarding D-dimer, ferritin, LDH, CRP, WBC, lymphocytes, PCV, and RBC (<em>P</em> < 0.05), while no significant differences were found for HB and platelet counts. The DD genotype was predominant (43.11 %), followed by ID (39.56 %) and II (17.33 %). Notably, a significant association was observed between D-dimer levels and ACE genotype (<em>P</em> < 0.0001), with higher levels observed in individuals with the DD genotype. Additionally, a significant correlation was found between ACE genotype and sex (<em>P</em> = 0.0163). No significant association was observed between genotype and ICU admission or lung CT severity.</div></div><div><h3>Conclusion</h3><div>Our findings suggest a potential link between the <em>ACE</em> D/D genotype and elevated D-dimer levels in COVID-19 patients, indicating a potential role for <em>ACE</em> gene polymorphism in influencing disease severity. Further research is warranted to elucidate the underlying mechanisms and explore the potential for personalized treatment approaches based on <em>ACE</em> genotype.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201344"},"PeriodicalIF":0.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号