Background: Drug-resistant hospital-acquired infections (HAIs) are a growing concern in modern medicine throughout the world. Klebsiella pneumoniae is one of the most prominent causative agents of multidrug-resistant nosocomial infections. It is also widely recognized for having a high resistance level to many antibiotic classes, particularly beta-lactams. Carbapenemase-producing K. pneumoniae has been identified as a major global cause of HAIs with adverse clinical outcomes. Therefore, it is of the utmost importance to have an in-depth understanding of the antimicrobial resistance (AMR) genetic determinants of this bacterium to stop the spread of highly resistant K. pneumoniae in healthcare facilities and the resulting patient morbidity and mortality. Objectives: This study aimed to investigate the AMR pattern of K. pneumoniae isolates obtained from intensive care units (ICUs), with a focus on extended-spectrum beta-lactamases (ESBLs) genes blaCTX-M, blaGES, and blaIMP. Methods: A total of 105 K. pneumoniae isolates obtained from the sputum samples of ICU patients were identified and confirmed using standard microbiological tests and 16S rRNA polymerase chain reaction (PCR). The antibiotic susceptibility test was performed for all the isolates. The presence of ESBL genes was determined phenotypically and by PCR. Results: The highest level of resistance was observed against ceftazidime (100%), cefotaxime (99%), and imipenem (93.3%). Approximately 87.6% and 39% of the isolates were sensitive to colistin and gentamicin, respectively. Phenotypic ESBL production was observed in 16 isolates, and the prevalence of blaCTX-M was 86.7%. No blaGES and blaIMP genes were detected. Conclusions: Periodic investigation of AMR-mediating genes is essential due to the high prevalence of ESBL genes in HAIs. The presence of other ESBL genes needs to be investigated for a more accurate understanding of the AMR status of K. pneumoniae in healthcare settings.
{"title":"Extended-Spectrum Beta-Lactamases Genes in Klebsiella pneumoniae Isolates Obtained from Patients in Intensive Care Units","authors":"Reyhaneh Taheri Tinjani, Milad Sabaei, Fatemeh Shamlou Mahmoudi, Soheil Rahmani Fard, Seyyed Khalil Shokouhi Mostafavi, Leyla Bahadorizadeh, Sara Minaeian","doi":"10.5812/jjm-140497","DOIUrl":"https://doi.org/10.5812/jjm-140497","url":null,"abstract":"Background: Drug-resistant hospital-acquired infections (HAIs) are a growing concern in modern medicine throughout the world. Klebsiella pneumoniae is one of the most prominent causative agents of multidrug-resistant nosocomial infections. It is also widely recognized for having a high resistance level to many antibiotic classes, particularly beta-lactams. Carbapenemase-producing K. pneumoniae has been identified as a major global cause of HAIs with adverse clinical outcomes. Therefore, it is of the utmost importance to have an in-depth understanding of the antimicrobial resistance (AMR) genetic determinants of this bacterium to stop the spread of highly resistant K. pneumoniae in healthcare facilities and the resulting patient morbidity and mortality. Objectives: This study aimed to investigate the AMR pattern of K. pneumoniae isolates obtained from intensive care units (ICUs), with a focus on extended-spectrum beta-lactamases (ESBLs) genes blaCTX-M, blaGES, and blaIMP. Methods: A total of 105 K. pneumoniae isolates obtained from the sputum samples of ICU patients were identified and confirmed using standard microbiological tests and 16S rRNA polymerase chain reaction (PCR). The antibiotic susceptibility test was performed for all the isolates. The presence of ESBL genes was determined phenotypically and by PCR. Results: The highest level of resistance was observed against ceftazidime (100%), cefotaxime (99%), and imipenem (93.3%). Approximately 87.6% and 39% of the isolates were sensitive to colistin and gentamicin, respectively. Phenotypic ESBL production was observed in 16 isolates, and the prevalence of blaCTX-M was 86.7%. No blaGES and blaIMP genes were detected. Conclusions: Periodic investigation of AMR-mediating genes is essential due to the high prevalence of ESBL genes in HAIs. The presence of other ESBL genes needs to be investigated for a more accurate understanding of the AMR status of K. pneumoniae in healthcare settings.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135345882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In liver transplant recipients, human Cytomegalovirus (CMV) infection is a significant concern. Ganciclovir is the preferred medication for treating widespread CMV infections. In some cases, patients might require high doses of treatment for CMV infections that are resistant to ganciclovir, although liver transplant patients who have received extended ganciclovir and valganciclovir prophylaxis have reported infrequent cases of ganciclovir-resistant CMV infections. Mutations in the UL54 gene, responsible for encoding deoxyribonucleic acid (DNA) polymerase, can result in resistance. Objectives: In this study, the focus was on UL54 mutations and their association with ganciclovir resistance. Methods: In this study, 23 liver transplant recipients who were admitted to the transplant departments of Namazi and Abu Ali Sina hospitals within 2015 and 2017 were examined. Cytomegalovirus infection was then confirmed in them using the quantitative real-time polymerase chain reaction (PCR) method. The UL54 mutations were found after electrophoresis using the nested PCR method, and the PCR products were subsequently sequenced using the Sanger method. Sequence analysis and locating of UL54 mutations were performed using Finch software (version 1.4.0). Results: After sequencing 52 samples from 23 patients, 25 mutations in the UL54 gene were identified in 9 patients who were CMV-infected, occurring at a median of 32 days after transplant. These mutations, including S655L (10/9, 40%), N685S (8/9, 32%), F669L (4/9, 16%), A688V (2/9, 8%), and the novel AK124703.1: p.V668-G672dup (1/9, 4%), were detected in 9 liver transplant recipients over a median period of 2 years in the UL54 gene. Furthermore, a phylogenetic analysis was conducted to investigate the origins of these mutations in CMV isolated from the Iranian population. Conclusions: Considering that treatment with the drug ganciclovir has led to resistance mutations, particularly the new AK124703.1:p.V668-G672dup mutation, and inefficiency in treatment, it is necessary to determine drug-resistant CMV strains and closely monitor these patients. This includes determining viral load, assessing response to treatment, and identifying non-response at regular intervals until the viral load is completely eradicated in order to ensure the effectiveness of the treatment.
背景:在肝移植受者中，人巨细胞病毒(CMV)感染是一个值得关注的问题。更昔洛韦是治疗广泛的巨细胞病毒感染的首选药物。在某些情况下，患者可能需要对更昔洛韦耐药的巨细胞病毒感染进行高剂量治疗，尽管肝移植患者接受了更昔洛韦和缬更昔洛韦的长期预防治疗，但报告了更昔洛韦耐药巨细胞病毒感染的罕见病例。负责编码脱氧核糖核酸(DNA)聚合酶的UL54基因的突变可导致耐药性。目的:本研究的重点是UL54突变及其与更昔洛韦耐药性的关系。方法:本研究对2015年至2017年在Namazi和Abu Ali Sina医院移植科住院的23例肝移植受者进行调查。采用实时荧光定量聚合酶链反应(PCR)法检测巨细胞病毒感染。用巢式PCR法电泳发现UL54突变，PCR产物用Sanger法测序。使用Finch软件(版本1.4.0)进行序列分析和定位UL54突变。结果:在对来自23例患者的52个样本进行测序后，在9例cmv感染患者中发现了25个UL54基因突变，这些突变发生在移植后32天。这些突变包括S655L(10/9, 40%)、N685S(8/9, 32%)、F669L(4/9, 16%)、A688V(2/9, 8%)和新型AK124703.1: p.V668-G672dup(1/9, 4%)，在UL54基因中位时间为2年的9例肝移植受者中检测到。此外，还进行了系统发育分析，以调查从伊朗人群中分离的巨细胞病毒中这些突变的起源。结论:考虑到更昔洛韦治疗已导致耐药突变，特别是新的AK124703.1:p。V668-G672dup突变，治疗效率低下，有必要确定耐药CMV菌株并密切监测这些患者。这包括确定病毒载量，评估对治疗的反应，并定期识别无反应，直到病毒载量完全根除，以确保治疗的有效性。
{"title":"A New Duplication in 668 to 672 Sites of UL54 Gene in Cytomegalovirus Ganciclovir Resistant Liver Transplanted Patients","authors":"Leila Jalilsani, Ramin Yaghobi, Bita Geramizadeh, Afsoon Afshari, Mohammadhossein Karimi","doi":"10.5812/jjm-137970","DOIUrl":"https://doi.org/10.5812/jjm-137970","url":null,"abstract":"Background: In liver transplant recipients, human Cytomegalovirus (CMV) infection is a significant concern. Ganciclovir is the preferred medication for treating widespread CMV infections. In some cases, patients might require high doses of treatment for CMV infections that are resistant to ganciclovir, although liver transplant patients who have received extended ganciclovir and valganciclovir prophylaxis have reported infrequent cases of ganciclovir-resistant CMV infections. Mutations in the UL54 gene, responsible for encoding deoxyribonucleic acid (DNA) polymerase, can result in resistance. Objectives: In this study, the focus was on UL54 mutations and their association with ganciclovir resistance. Methods: In this study, 23 liver transplant recipients who were admitted to the transplant departments of Namazi and Abu Ali Sina hospitals within 2015 and 2017 were examined. Cytomegalovirus infection was then confirmed in them using the quantitative real-time polymerase chain reaction (PCR) method. The UL54 mutations were found after electrophoresis using the nested PCR method, and the PCR products were subsequently sequenced using the Sanger method. Sequence analysis and locating of UL54 mutations were performed using Finch software (version 1.4.0). Results: After sequencing 52 samples from 23 patients, 25 mutations in the UL54 gene were identified in 9 patients who were CMV-infected, occurring at a median of 32 days after transplant. These mutations, including S655L (10/9, 40%), N685S (8/9, 32%), F669L (4/9, 16%), A688V (2/9, 8%), and the novel AK124703.1: p.V668-G672dup (1/9, 4%), were detected in 9 liver transplant recipients over a median period of 2 years in the UL54 gene. Furthermore, a phylogenetic analysis was conducted to investigate the origins of these mutations in CMV isolated from the Iranian population. Conclusions: Considering that treatment with the drug ganciclovir has led to resistance mutations, particularly the new AK124703.1:p.V668-G672dup mutation, and inefficiency in treatment, it is necessary to determine drug-resistant CMV strains and closely monitor these patients. This includes determining viral load, assessing response to treatment, and identifying non-response at regular intervals until the viral load is completely eradicated in order to ensure the effectiveness of the treatment.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135476243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kazem Savojbolaghchi Khiabani, Niloofar Neisi, Shahrokh Raiesian, Houman Sina, Mohammad Hosein Amirzade-Iranaq
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmits when aerosols or droplets containing the virus are inhaled or come directly into contact, mainly in close contact with an infected person. Objectives: This study aimed to evaluate the role of the salivary glands in the secretion of SARS-CoV-2-infected saliva and determine the contagiousness of saliva in asymptomatic coronavirus disease 2019 (COVID-19) patients. Methods: In this cross-sectional analytical study between March 2021 and March 2022, 85 asymptomatic COVID-19 individuals with positive nasopharyngeal/oropharyngeal swabs were recruited. The SARS-CoV-2 cycle threshold (Ct) value was investigated in concomitant nasopharyngeal swabs (NPS), saliva, and pure saliva (collected directly from the salivary duct opening) using Real Time-PCR assay. Statistical analysis was performed using SPSS software (version 23), and a p-value of < 0.05 was considered significant. Results: The saliva Ct-value was the lowest (the highest viral load) for Delta (29.82 ± 4.66), Omicron (32.75 ± 4.82), and Alpha (36.83 ± 4.8) variants, respectively. Delta-infected saliva and pure saliva revealed the strongest correlation (correlation coefficient = 0.971, P < 0.001). Saliva Ct-value was significantly lower in Delta- (P < 0.001) and Omicron- (P = 0.012) infected patients than in Alpha-infected patients. The pure saliva Ct-value was significantly lower (P = 0.014) in Delta samples (30.13 ± 4.51). Asymptomatic Alpha- and Omicron-infected patients revealed significantly lower NPS Ct-value (30.52 ± 4.02 and 29.44 ± 3.34) than the saliva (36.83 ± 4.8 and 32.75 ± 4.82). Conclusions: The major salivary glands secrete SARS-CoV-2-infected saliva in nearly all Delta-infected and most Omicron-infected asymptomatic individuals. Although the transmission process is complex, saliva droplets and aerosols seem to have a higher contagiousness potential in individuals infected with the Delta variant.
{"title":"Assessment of Salivary Glands as Reservoirs of SARS-CoV-2 and the Contagiousness of Saliva in Asymptomatic COVID-19 Patients: Is Delta Variant More Contagious?","authors":"Kazem Savojbolaghchi Khiabani, Niloofar Neisi, Shahrokh Raiesian, Houman Sina, Mohammad Hosein Amirzade-Iranaq","doi":"10.5812/jjm-139773","DOIUrl":"https://doi.org/10.5812/jjm-139773","url":null,"abstract":"Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection transmits when aerosols or droplets containing the virus are inhaled or come directly into contact, mainly in close contact with an infected person. Objectives: This study aimed to evaluate the role of the salivary glands in the secretion of SARS-CoV-2-infected saliva and determine the contagiousness of saliva in asymptomatic coronavirus disease 2019 (COVID-19) patients. Methods: In this cross-sectional analytical study between March 2021 and March 2022, 85 asymptomatic COVID-19 individuals with positive nasopharyngeal/oropharyngeal swabs were recruited. The SARS-CoV-2 cycle threshold (Ct) value was investigated in concomitant nasopharyngeal swabs (NPS), saliva, and pure saliva (collected directly from the salivary duct opening) using Real Time-PCR assay. Statistical analysis was performed using SPSS software (version 23), and a p-value of < 0.05 was considered significant. Results: The saliva Ct-value was the lowest (the highest viral load) for Delta (29.82 ± 4.66), Omicron (32.75 ± 4.82), and Alpha (36.83 ± 4.8) variants, respectively. Delta-infected saliva and pure saliva revealed the strongest correlation (correlation coefficient = 0.971, P < 0.001). Saliva Ct-value was significantly lower in Delta- (P < 0.001) and Omicron- (P = 0.012) infected patients than in Alpha-infected patients. The pure saliva Ct-value was significantly lower (P = 0.014) in Delta samples (30.13 ± 4.51). Asymptomatic Alpha- and Omicron-infected patients revealed significantly lower NPS Ct-value (30.52 ± 4.02 and 29.44 ± 3.34) than the saliva (36.83 ± 4.8 and 32.75 ± 4.82). Conclusions: The major salivary glands secrete SARS-CoV-2-infected saliva in nearly all Delta-infected and most Omicron-infected asymptomatic individuals. Although the transmission process is complex, saliva droplets and aerosols seem to have a higher contagiousness potential in individuals infected with the Delta variant.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135683875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiman Karami, Vahid Asghariazar, Yasamin Pahlavan, Kamyar Mazloum Jalali, Ahmad Tajehmiri, Mohammad GhorbaniVanan, Elham Safarzadeh
Background: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been undergoing variation. Most of the variants cause no concern for human health. Some others have had worse outcomes in terms of transmissibility, vaccination resistance, and, generally, the survival of patients infected with SARS-CoV-2. Objectives: This study investigated the mutation of interest in the receptor-binding domain (RBD) of SARS-CoV-2. Methods: Ribonucleic acid (RNA) was extracted from 40 swap samples. Next, the polymerase chain reaction (PCR) assay was carried out to detect the RBD. Investigation of SARS-COV-2 RBD was performed completely by phylogenetic and tree alignment. The multiple sequence alignment (MSA) of the biological sequence of RBD was created by BioEdit, Snap Gene, and MEGA software and was then compared to sequences of different variants of SARS-COV-2 in the GenBank (National Center for Biotechnology Information). The Influenza Surveillance and Response System (GSAID) was used to detect mutations in the RBD sequence. Results: Multiple sequence alignment (MSA) RBD domain showed that the RBD domain sequence obtained from the Iranian patients' highest identity by severe acute respiratory syndrome coronavirus 2 isolate MZ907347. Several mutations of interest, including A475V, L452R, V483A, and F490L, were detected in the RBD region. However, the dN/dS analysis detected positive selection in RBD regions. Conclusions: Amino acid changes in the surface protein can significantly alter the viral function and/or interactions with neutralizing antibodies. Most of the nucleotide changes in the spike gene reduce infectivity. The V503W and P521Q mutations reduce infectivity, the A522Q mutation increases sensitivity to neutralizing antibodies, and the H519T mutation decreases susceptibility to convalescent sera.
背景:严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)刺突蛋白发生变异。大多数变异对人体健康没有影响。其他一些在传播性、疫苗耐药性以及感染SARS-CoV-2的患者的总体存活率方面的结果更差。目的:研究SARS-CoV-2受体结合域(receptor-binding domain, RBD)的突变。方法:从40份交换样品中提取核糖核酸(RNA)。接下来，采用聚合酶链反应(PCR)检测RBD。SARS-COV-2 RBD的调查完全通过系统发育和树比对进行。RBD生物序列的多序列比对(MSA)由BioEdit、Snap Gene和MEGA软件创建，然后与GenBank (National Center for Biotechnology Information)中SARS-COV-2不同变体的序列进行比较。流感监测和反应系统(GSAID)用于检测RBD序列的突变。结果:多序列比对(MSA)显示，严重急性呼吸综合征冠状病毒2型分离物MZ907347从伊朗患者获得的RBD结构域序列最高。在RBD区域检测到几个感兴趣的突变，包括A475V、L452R、V483A和F490L。然而，dN/dS分析在RBD区域检测到阳性选择。结论:表面蛋白氨基酸的改变可以显著改变病毒的功能和/或与中和抗体的相互作用。刺突基因的大部分核苷酸变化都降低了传染性。V503W和P521Q突变降低传染性，A522Q突变增加对中和抗体的敏感性，H519T突变降低对恢复期血清的敏感性。
{"title":"Mutation Interest in the Receptor-Binding Domain of Spike Protein of Severe Acute Respiratory Syndrome Coronavirus 2 in the Northwest of Iran","authors":"Chiman Karami, Vahid Asghariazar, Yasamin Pahlavan, Kamyar Mazloum Jalali, Ahmad Tajehmiri, Mohammad GhorbaniVanan, Elham Safarzadeh","doi":"10.5812/jjm-137863","DOIUrl":"https://doi.org/10.5812/jjm-137863","url":null,"abstract":"Background: The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been undergoing variation. Most of the variants cause no concern for human health. Some others have had worse outcomes in terms of transmissibility, vaccination resistance, and, generally, the survival of patients infected with SARS-CoV-2. Objectives: This study investigated the mutation of interest in the receptor-binding domain (RBD) of SARS-CoV-2. Methods: Ribonucleic acid (RNA) was extracted from 40 swap samples. Next, the polymerase chain reaction (PCR) assay was carried out to detect the RBD. Investigation of SARS-COV-2 RBD was performed completely by phylogenetic and tree alignment. The multiple sequence alignment (MSA) of the biological sequence of RBD was created by BioEdit, Snap Gene, and MEGA software and was then compared to sequences of different variants of SARS-COV-2 in the GenBank (National Center for Biotechnology Information). The Influenza Surveillance and Response System (GSAID) was used to detect mutations in the RBD sequence. Results: Multiple sequence alignment (MSA) RBD domain showed that the RBD domain sequence obtained from the Iranian patients' highest identity by severe acute respiratory syndrome coronavirus 2 isolate MZ907347. Several mutations of interest, including A475V, L452R, V483A, and F490L, were detected in the RBD region. However, the dN/dS analysis detected positive selection in RBD regions. Conclusions: Amino acid changes in the surface protein can significantly alter the viral function and/or interactions with neutralizing antibodies. Most of the nucleotide changes in the spike gene reduce infectivity. The V503W and P521Q mutations reduce infectivity, the A522Q mutation increases sensitivity to neutralizing antibodies, and the H519T mutation decreases susceptibility to convalescent sera.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135634616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Human rhinovirus (HRV) and human metapneumovirus (hMPV) are common viral causes of pediatric respiratory tract infections. Bacterial co-infections frequently complicate HRV and hMPV illnesses in children, but the interactions between viral and bacterial pathogens and their impacts on disease severity are not well understood. Objectives: The present research aimed to analyze and compare the clinical features of HRV and hMPV mono-infections in hospitalized children and to assess the impact of bacterial co-infection on the disease severity of HRV and hMPV infections. Methods: The present retrospective analytical cross-sectional study was conducted to compare the clinical features between HRV and hMPV mono-infections and HRV and hMPV with bacterial co-infections in hospitalized children aged 14 years or younger. Results: Between January and December 2022, we investigated 1,978 children hospitalized with HRV infection, of which 1,529 had HRV mono-infection and 1,117 hospitalized with hMPV infection, among whom 910 had hMPV mono-infection. Compared to HRV, hMPV mono-infection exhibited more pronounced symptoms of fever, cough, and rales in most age groups, while HRV showed more wheezing. Except in patients ≥ 6 years old, hMPV was more associated with pneumonia and longer hospitalizations. In contrast to HRV mono-infections, children with bacterial co-infections had a higher proportion of coughs (P < 0.001), pneumonia (P < 0.001), pediatric intensive care unit (PICU) admissions (P < 0.001), and longer hospitalizations (P = 0.003). Demographic characteristics, clinical presentation, diagnosis, and treatments showed no significant differences between patients with hMPV mono-infection and co-infection. Conclusions: Among hospitalized children, hMPV mono-infection resulted in more severe respiratory illnesses compared to HRV mono-infection. Bacterial co-infections exacerbated disease severity in HRV infections.
{"title":"The Impact of Bacterial Co-Infection on Hospitalized Children with Human Rhinovirus and Human Metapneumovirus Infections: A Retrospective Analytical Cross-Sectional Study","authors":"Qing Wan, Ya-wei Li, Ying Cheng, Hongbo Hu","doi":"10.5812/jjm-139106","DOIUrl":"https://doi.org/10.5812/jjm-139106","url":null,"abstract":"Background: Human rhinovirus (HRV) and human metapneumovirus (hMPV) are common viral causes of pediatric respiratory tract infections. Bacterial co-infections frequently complicate HRV and hMPV illnesses in children, but the interactions between viral and bacterial pathogens and their impacts on disease severity are not well understood. Objectives: The present research aimed to analyze and compare the clinical features of HRV and hMPV mono-infections in hospitalized children and to assess the impact of bacterial co-infection on the disease severity of HRV and hMPV infections. Methods: The present retrospective analytical cross-sectional study was conducted to compare the clinical features between HRV and hMPV mono-infections and HRV and hMPV with bacterial co-infections in hospitalized children aged 14 years or younger. Results: Between January and December 2022, we investigated 1,978 children hospitalized with HRV infection, of which 1,529 had HRV mono-infection and 1,117 hospitalized with hMPV infection, among whom 910 had hMPV mono-infection. Compared to HRV, hMPV mono-infection exhibited more pronounced symptoms of fever, cough, and rales in most age groups, while HRV showed more wheezing. Except in patients ≥ 6 years old, hMPV was more associated with pneumonia and longer hospitalizations. In contrast to HRV mono-infections, children with bacterial co-infections had a higher proportion of coughs (P < 0.001), pneumonia (P < 0.001), pediatric intensive care unit (PICU) admissions (P < 0.001), and longer hospitalizations (P = 0.003). Demographic characteristics, clinical presentation, diagnosis, and treatments showed no significant differences between patients with hMPV mono-infection and co-infection. Conclusions: Among hospitalized children, hMPV mono-infection resulted in more severe respiratory illnesses compared to HRV mono-infection. Bacterial co-infections exacerbated disease severity in HRV infections.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136023528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Listeria monocytogenes (LM) is a facultative intracellular pathogen that causes food-borne infections in humans and animals. To invade and multiply within host cells, LM utilizes various strategies to precisely modulate its gene expression and to adapt to the in vivo environment. Objectives: To investigate the regulatory roles of Rli82 sRNA in the motility and pathogenicity of LM EGD-e. Methods: The Rli82 gene knock-out mutant strain, LM-ΔRli82, and the complementation strain, LM-ΔRli82/Rli82, were constructed using homologous recombination technology, and their motility and virulence, respectively, were determined. Moreover, the potential target mRNA regulated by Rli82 was predicted using TargetRNA2 software, and then the interaction between the target mRNA and Rli82 was verified by the two-plasmid reporter system. Results: The results showed that the motility of LM-ΔRli82 was significantly increased at 25°C, facilitated by the production of more flagella than LM EGD-e and LM-ΔRli82/Rli82. Furthermore, LD50 in LM-ΔRli82-infected mice was significantly increased as compared to LM EGD-e and LM-ΔRli82/Rli82, suggesting that the virulence of LM was weakened when the Rli82 gene was deleted. In addition, the mRNA level of flaA was not significantly elevated, but flaA protein was significantly higher in LM-ΔRli82 than in LM EGD-e and LM-ΔRli82/Rli82, suggesting that Rli82 might modulate the translation of flaA mRNA at the post-transcriptional level. Conclusions: Taken together, our findings for the first time revealed that Rli82 sRNA might be involved in the modulation of the expression of flaA protein, thereby influencing the mobility and pathogenicity of LM.
{"title":"A Small Regulatory RNA, Rli82, Is Involved in the Motility and Pathogenicity of Listeria monocytogenes","authors":"Chunhui Ji, Nengxiu Li, Jian Jiao, Yaoqiang Sun, Yufei Zuo, Xin Huang, Xiaoxing Huang, Zhiyuan Li, Yaling Li, Qingwen Leng, Xuepeng Cai, Q. Meng, Jun Qiao","doi":"10.5812/jjm-139707","DOIUrl":"https://doi.org/10.5812/jjm-139707","url":null,"abstract":"Background: Listeria monocytogenes (LM) is a facultative intracellular pathogen that causes food-borne infections in humans and animals. To invade and multiply within host cells, LM utilizes various strategies to precisely modulate its gene expression and to adapt to the in vivo environment. Objectives: To investigate the regulatory roles of Rli82 sRNA in the motility and pathogenicity of LM EGD-e. Methods: The Rli82 gene knock-out mutant strain, LM-ΔRli82, and the complementation strain, LM-ΔRli82/Rli82, were constructed using homologous recombination technology, and their motility and virulence, respectively, were determined. Moreover, the potential target mRNA regulated by Rli82 was predicted using TargetRNA2 software, and then the interaction between the target mRNA and Rli82 was verified by the two-plasmid reporter system. Results: The results showed that the motility of LM-ΔRli82 was significantly increased at 25°C, facilitated by the production of more flagella than LM EGD-e and LM-ΔRli82/Rli82. Furthermore, LD50 in LM-ΔRli82-infected mice was significantly increased as compared to LM EGD-e and LM-ΔRli82/Rli82, suggesting that the virulence of LM was weakened when the Rli82 gene was deleted. In addition, the mRNA level of flaA was not significantly elevated, but flaA protein was significantly higher in LM-ΔRli82 than in LM EGD-e and LM-ΔRli82/Rli82, suggesting that Rli82 might modulate the translation of flaA mRNA at the post-transcriptional level. Conclusions: Taken together, our findings for the first time revealed that Rli82 sRNA might be involved in the modulation of the expression of flaA protein, thereby influencing the mobility and pathogenicity of LM.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.6,"publicationDate":"2023-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139311519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Onychomycosis is one of the most common fungal infections. The most common etiological agents of onychomycosis in Iran are Candida species, especially fingernails. It is more common in women than men, particularly workers in occupations requiring them to submerge their hands or feet in water for prolonged periods. Objectives: The current study's main aim was to determine the abundance of candidal onychomycosis, identify the Candida species using molecular methods, and evaluate the in vitro antifungal susceptibility profiles. Methods: One hundred forty samples were obtained from patients suspected of onychomycosis, and 51 (36.4%) Candida strains were identified by PCR-RFLP. The in vitro susceptibility of four triazole (FLC, ITC, VRC, and POS) antifungal drug testing of 51 Candida species was performed using broth microdilution. Results: Direct microscopic examination by KOH 20% of 140 nail samples showed that 51 (36.4%) samples were positive in terms of fungal elements, with Candida parapsilosis complex being the most frequently isolated of patients, followed by C. albicans complex, C. glabrata, C. krusei, C. tropicalis, C. guilliermondii, C. famata, C. kefyr, and Candida species. All Candida species showed they were susceptible to four triazoles, except that five C. krusei were resistant to fluconazole. Only one C. glabrata isolates and one C. parapsilosis isolate were resistant to fluconazole. Conclusions: The growing trend towards the frequency of fingernail onychomycosis in housewives has been noticeable in the last decades in Iran. Therefore, accurate identification of Candida species and perform in vitro antifungal susceptibility testing can aid physicians in choosing an effective potential drug for treating onychomycosis patients.
{"title":"Molecular Identification of Candida Species Isolated from Onychomycosis with In Vitro Antifungal Susceptibility Profiles","authors":"Mohammad Hosein Afsarian, Zahra Sharafi","doi":"10.5812/jjm-139906","DOIUrl":"https://doi.org/10.5812/jjm-139906","url":null,"abstract":"Background: Onychomycosis is one of the most common fungal infections. The most common etiological agents of onychomycosis in Iran are Candida species, especially fingernails. It is more common in women than men, particularly workers in occupations requiring them to submerge their hands or feet in water for prolonged periods. Objectives: The current study's main aim was to determine the abundance of candidal onychomycosis, identify the Candida species using molecular methods, and evaluate the in vitro antifungal susceptibility profiles. Methods: One hundred forty samples were obtained from patients suspected of onychomycosis, and 51 (36.4%) Candida strains were identified by PCR-RFLP. The in vitro susceptibility of four triazole (FLC, ITC, VRC, and POS) antifungal drug testing of 51 Candida species was performed using broth microdilution. Results: Direct microscopic examination by KOH 20% of 140 nail samples showed that 51 (36.4%) samples were positive in terms of fungal elements, with Candida parapsilosis complex being the most frequently isolated of patients, followed by C. albicans complex, C. glabrata, C. krusei, C. tropicalis, C. guilliermondii, C. famata, C. kefyr, and Candida species. All Candida species showed they were susceptible to four triazoles, except that five C. krusei were resistant to fluconazole. Only one C. glabrata isolates and one C. parapsilosis isolate were resistant to fluconazole. Conclusions: The growing trend towards the frequency of fingernail onychomycosis in housewives has been noticeable in the last decades in Iran. Therefore, accurate identification of Candida species and perform in vitro antifungal susceptibility testing can aid physicians in choosing an effective potential drug for treating onychomycosis patients.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135219267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Choon-Mee Kim, Seul-Bi Lee, Young-Jin Ko, Seong-Ho Kang, Geon Park, Sook-Jin Jang
Background: Antibacterial peptides have a broad antibacterial spectrum and are not affected by classical resistance mechanisms; therefore, they can be used in combination with classic antibiotics to treat multidrug-resistant Acinetobacter baumannii infections, making them an alternative for the development of new therapeutic strategies. Objectives: This study aimed to assess the effectiveness of combining amphiphilic peptides, specifically C12-prp and mastoparan, with antibiotics in combating A. baumannii clinical isolates. Methods: We investigated combinations that inhibited the growth of A. baumannii clinical isolates, consisting of 24 extensively drug-resistant (XDR) and 11 pan-drug-resistant (PDR) strains collected between January 2004 and December 2014 at Chosun University Hospital using a multiple combination bactericidal test (MCBT). A time-kill study was used to confirm the bactericidal activity and synergism of the four combinations selected via MCBT. Results: Four combinations (C12-prp-colistin, C12-prp-rifampicin, mastoparan-colistin, and mastoparan-rifampicin) showed 100% (24/24) synergy with XDR A. baumannii strains. However, in the case of the PDR strains, only two combinations, C12-prp-colistin and mastoparan-colistin, showed a 9.1% (1/11) synergy. Moreover, the mastoparan-colistin and mastoparan-rifampicin combinations showed 100% (24/24) bactericidal activity against the XDR A. baumannii strains, whereas the C12-prp-colistin and C12-prp-rifampicin combinations showed 91.7% (22/24) bactericidal activity. None of the combinations showed bactericidal activity against PDR strains. Conclusions: Our study highlighted the substantial synergistic antibacterial efficacy of C12-prp and mastoparan peptides when combined with colistin or rifampicin. Furthermore, this approach could be a promising alternative for developing new treatment strategies for XDR A. baumannii infections.
{"title":"Synergistic Peptide-Antibiotic Approach to Combat Multidrug-Resistant Acinetobacter baumannii","authors":"Choon-Mee Kim, Seul-Bi Lee, Young-Jin Ko, Seong-Ho Kang, Geon Park, Sook-Jin Jang","doi":"10.5812/jjm-136712","DOIUrl":"https://doi.org/10.5812/jjm-136712","url":null,"abstract":"Background: Antibacterial peptides have a broad antibacterial spectrum and are not affected by classical resistance mechanisms; therefore, they can be used in combination with classic antibiotics to treat multidrug-resistant Acinetobacter baumannii infections, making them an alternative for the development of new therapeutic strategies. Objectives: This study aimed to assess the effectiveness of combining amphiphilic peptides, specifically C12-prp and mastoparan, with antibiotics in combating A. baumannii clinical isolates. Methods: We investigated combinations that inhibited the growth of A. baumannii clinical isolates, consisting of 24 extensively drug-resistant (XDR) and 11 pan-drug-resistant (PDR) strains collected between January 2004 and December 2014 at Chosun University Hospital using a multiple combination bactericidal test (MCBT). A time-kill study was used to confirm the bactericidal activity and synergism of the four combinations selected via MCBT. Results: Four combinations (C12-prp-colistin, C12-prp-rifampicin, mastoparan-colistin, and mastoparan-rifampicin) showed 100% (24/24) synergy with XDR A. baumannii strains. However, in the case of the PDR strains, only two combinations, C12-prp-colistin and mastoparan-colistin, showed a 9.1% (1/11) synergy. Moreover, the mastoparan-colistin and mastoparan-rifampicin combinations showed 100% (24/24) bactericidal activity against the XDR A. baumannii strains, whereas the C12-prp-colistin and C12-prp-rifampicin combinations showed 91.7% (22/24) bactericidal activity. None of the combinations showed bactericidal activity against PDR strains. Conclusions: Our study highlighted the substantial synergistic antibacterial efficacy of C12-prp and mastoparan peptides when combined with colistin or rifampicin. Furthermore, this approach could be a promising alternative for developing new treatment strategies for XDR A. baumannii infections.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135463074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahdi Dadashi Firouzjaei, Peyman Hendizadeh, Mehrdad Halaji, Sajad Yaghoubi, Mohammad Teimourian, Akramossadat Hosseini, Mehdi Rajabnia, Abazar Pournajaf
Background: Klebsiella pneumoniae is a bacterium that commonly causes urinary tract infections (UTIs) in hospital settings. The widespread and improper usage of quinolones has increased the resistance rates against these broad-spectrum antibiotics. Objectives: This study aimed to examine the connection between the ability to form biofilms and fluoroquinolone resistance in K. pneumoniae isolated from catheter-associated UTIs. Methods: A total of 110 nonduplicative K. pneumoniae-related catheter-associated UTIs were isolated from three large educational hospitals in Babol, north of Iran. The minimal inhibitory concentration (MIC) of ciprofloxacin was calculated for each detected isolate using the agar dilution procedure. Biofilm production was investigated by a 96-well flat-bottom microtiter plate. The prevalence of gyrA, parC, qnrA, qnrS, acc (6’)-Ib-cr, qepA, qnrB, oqxA, and oqxB genes was evaluated using polymerase chain reaction (PCR). Results: Overall, 28.2% of the strains were resistant to imipenem and considered carbapenem-resistant K. pneumoniae (CRKp). Ciprofloxacin resistance was observed in 66.4%. Moreover, 70% of the isolates produced biofilm. Biofilm production was significantly higher in ciprofloxacin-resistant compared to ciprofloxacin-susceptible strains (P-value < 0.05). Molecular distribution of resistance genes in the 68-fluoroquinolone resistance-Kp strains showed that the prevalence of gyrA, parC, qnrA, qnrS, acc (6’)-Ib-cr, qepA,, qnrB, oqxA, and oqxB genes was 39.7%, 42.6%, 5.9%, 54.4%, 69.1%, 94.1%, 41.2%, 69.1%, and 83.8%, respectively. Conclusions: Our study highlights the high prevalence of plasmid-mediated quinolone resistance genes in clinical samples of K. pneumoniae in the studied region, which is alarming given the possibility of the spread of these pathogens and the few treatments available for infections brought on by multidrug-resistant strains. Moreover, the study characterizes particular mutations in the parC and gyrA genes that cause quinolone resistance.
{"title":"Quinolone Resistance in Biofilm-Forming Klebsiella pneumoniae-Related Catheter-Associated Urinary Tract Infections: A Neglected Problem","authors":"Mahdi Dadashi Firouzjaei, Peyman Hendizadeh, Mehrdad Halaji, Sajad Yaghoubi, Mohammad Teimourian, Akramossadat Hosseini, Mehdi Rajabnia, Abazar Pournajaf","doi":"10.5812/jjm-136170","DOIUrl":"https://doi.org/10.5812/jjm-136170","url":null,"abstract":"Background: Klebsiella pneumoniae is a bacterium that commonly causes urinary tract infections (UTIs) in hospital settings. The widespread and improper usage of quinolones has increased the resistance rates against these broad-spectrum antibiotics. Objectives: This study aimed to examine the connection between the ability to form biofilms and fluoroquinolone resistance in K. pneumoniae isolated from catheter-associated UTIs. Methods: A total of 110 nonduplicative K. pneumoniae-related catheter-associated UTIs were isolated from three large educational hospitals in Babol, north of Iran. The minimal inhibitory concentration (MIC) of ciprofloxacin was calculated for each detected isolate using the agar dilution procedure. Biofilm production was investigated by a 96-well flat-bottom microtiter plate. The prevalence of gyrA, parC, qnrA, qnrS, acc (6’)-Ib-cr, qepA, qnrB, oqxA, and oqxB genes was evaluated using polymerase chain reaction (PCR). Results: Overall, 28.2% of the strains were resistant to imipenem and considered carbapenem-resistant K. pneumoniae (CRKp). Ciprofloxacin resistance was observed in 66.4%. Moreover, 70% of the isolates produced biofilm. Biofilm production was significantly higher in ciprofloxacin-resistant compared to ciprofloxacin-susceptible strains (P-value < 0.05). Molecular distribution of resistance genes in the 68-fluoroquinolone resistance-Kp strains showed that the prevalence of gyrA, parC, qnrA, qnrS, acc (6’)-Ib-cr, qepA,, qnrB, oqxA, and oqxB genes was 39.7%, 42.6%, 5.9%, 54.4%, 69.1%, 94.1%, 41.2%, 69.1%, and 83.8%, respectively. Conclusions: Our study highlights the high prevalence of plasmid-mediated quinolone resistance genes in clinical samples of K. pneumoniae in the studied region, which is alarming given the possibility of the spread of these pathogens and the few treatments available for infections brought on by multidrug-resistant strains. Moreover, the study characterizes particular mutations in the parC and gyrA genes that cause quinolone resistance.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135996097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Despite the global vaccination program, there are many new cases of pertussis in different societies annually. Objectives: This study aimed to investigate the prevalence of some microorganisms associated with pertussis-like syndrome and compare the clinical presentations between Bordetella pertussis and pertussis-like syndrome in children. Methods: Children younger than 5 years old suspected of pertussis-like syndrome were admitted to a hospital in Ahvaz, Iran, and examined from July 2018 to July 2019. Nasopharyngeal samples were evaluated using molecular methods. The studied microorganisms were the following: B. pertussis, B. parapertussis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, adenovirus, respiratory syncytial virus, and parainfluenza virus type III. Results: Forty-five children were enrolled. B. pertussis was detected in 15 cases (33.3%), respiratory syncytial virus in 14 (31.1%), C. pneumoniae in 3 (6.7%), and parainfluenza virus type III in 3 (6.7%). The collected samples were negative in terms of M. pneumoniae, adenovirus, and B. parapertussis. In the case of paroxysmal cough, the clinical symptoms were significantly different between pertussis and pertussis-like groups. Conclusions: The results indicated that children with pertussis-like syndrome are commonly infected with B. pertussis and respiratory syncytial virus, so more attention should be paid to this issue. The study also demonstrated the importance of molecular diagnosis methods, along with diagnosis based on clinical symptoms, in children suspected of pertussis-like syndrome.
{"title":"Identification of Etiological Agents of Pertussis-Like Syndrome in Children Younger Than 5 Years Old Hospitalized in Southwestern Iran","authors":"Ahmad Shamsizadeh, Roya Nikfar, Elham Bavarsadiankhah, Effat Abbasi-Montazeri, Niloofar Neisi, Maniya Arshadi","doi":"10.5812/jjm-130146","DOIUrl":"https://doi.org/10.5812/jjm-130146","url":null,"abstract":"Background: Despite the global vaccination program, there are many new cases of pertussis in different societies annually. Objectives: This study aimed to investigate the prevalence of some microorganisms associated with pertussis-like syndrome and compare the clinical presentations between Bordetella pertussis and pertussis-like syndrome in children. Methods: Children younger than 5 years old suspected of pertussis-like syndrome were admitted to a hospital in Ahvaz, Iran, and examined from July 2018 to July 2019. Nasopharyngeal samples were evaluated using molecular methods. The studied microorganisms were the following: B. pertussis, B. parapertussis, Mycoplasma pneumoniae, Chlamydophila pneumoniae, adenovirus, respiratory syncytial virus, and parainfluenza virus type III. Results: Forty-five children were enrolled. B. pertussis was detected in 15 cases (33.3%), respiratory syncytial virus in 14 (31.1%), C. pneumoniae in 3 (6.7%), and parainfluenza virus type III in 3 (6.7%). The collected samples were negative in terms of M. pneumoniae, adenovirus, and B. parapertussis. In the case of paroxysmal cough, the clinical symptoms were significantly different between pertussis and pertussis-like groups. Conclusions: The results indicated that children with pertussis-like syndrome are commonly infected with B. pertussis and respiratory syncytial virus, so more attention should be paid to this issue. The study also demonstrated the importance of molecular diagnosis methods, along with diagnosis based on clinical symptoms, in children suspected of pertussis-like syndrome.","PeriodicalId":17803,"journal":{"name":"Jundishapur Journal of Microbiology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136115929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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