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Rosai-Dorfman Disease With Pure and Multifocal Cutaneous Lesions: A Case Report Rosai-Dorfman病伴单纯多灶性皮肤病变1例报告
Q3 Medicine Pub Date : 2023-07-12 DOI: 10.18502/acta.v61i4.13177
D. Chebbi, S. Marzouk, R. B. Salah, I. Chabchoub, M. Snoussi, Z. Bahloul
A 52‐year‐old woman developed progressive infiltrated purple and hyperpigmented cutaneous lesions in the face, thighs, armpits, chest, and abdomen evolving forone year. Histopathological examination showed large histiocytes exhibiting intact inflammatory cells in their cytoplasm (emperipolesis). Immunohistochemical analyses showed that the histiocyte population was positive for S100 and CD68, but negative for CD1a. Based on the clinical, histopathological, and immunohistochemical findings, we made the diagnosis of Rosai Dorfman disease (RDD). Our patient didn’t manifest any other extra-cutaneous involvement and all the biological and radiological investigations were normal. This form of pure cutaneous RDD (P-CRDD) with multifocal lesions has been rarely reported. RDD is very rare and hardly recognized in the absence of lymphadenopathy. The diagnosis of this entity involves a combination of histology and immunohistochemistry. To date, there is no standard treatment.
一名52岁的女性面部、大腿、腋下、胸部和腹部出现渐进性紫色和色素沉着皮肤病变,持续一年。组织病理学检查显示大的组织细胞在其细胞质中表现出完整的炎症细胞(犬瘟热)。免疫组织化学分析显示组织细胞群S100和CD68阳性,CD1a阴性。根据临床、组织病理学和免疫组织化学结果,我们对Rosai Dorfman病(RDD)进行了诊断。我们的患者没有表现出任何其他皮肤外受累,所有的生物学和放射学检查都是正常的。这种具有多灶性病变的纯皮肤RDD(P-CRDD)很少报道。RDD非常罕见,在没有淋巴结病的情况下很难被识别。这种实体的诊断涉及组织学和免疫组织化学的结合。到目前为止,还没有标准的治疗方法。
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引用次数: 0
Is the ChAdOx1 Vaccine Safe and Immunogenic as Prophylactic Measure Against the Lethal Human-Coronaviruses? A Systematic Review ChAdOx1疫苗作为针对致命人类冠状病毒的预防措施是否安全且具有免疫原性?系统综述
Q3 Medicine Pub Date : 2023-07-12 DOI: 10.18502/acta.v61i4.13169
Andréia Michelle Alves Cunha de Alcântara, Ivan de Alcântara Barbosa Barros, Luiz Paulo de Souza Prazeres, Ivan de Alcântara Barbosa Barros, Maria Mascena Diniz Maia, P. R. Eleutério de Souza
Knowledge of other Coronaviruses has contributed to the development of a vaccine for the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). As soon as the genetic sequence of SARS-CoV-2 was released, intense global activity around different vaccine platform technologies started. Among these platforms, the viral vectored chimpanzee adenovirus Oxford1 (ChAdOx1)-previously studied for various indications, including for the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine, and currently is adapted for the ChAdOx1 nCoV-19 (novel Coronavirus-19). Therefore, this systematic review aimed to investigate the potential of the ChAdOx1 platform for the development of a vaccine for SARS-CoV and MERS-CoV, the Lethal Human-Coronaviruses (Lh-CoVs). For this purpose, a highly sensitive literary search was conducted through electronic databases that reached 1,445 related articles, of which, eight articles were elected according to previous eligibility criteria. The gathering of the articles demonstrated that the previous approaches, referring to the ChAdox1 platform, have contributed to the development of vaccines against Lh-CoVs and, that thus far, ChAdOx1 (nCoV-19 and MERS) vaccines are safe and immunogenic. However, it is important to emphasize that further studies are needed to ensure the effectiveness of vaccines in humans.
对其他冠状病毒的了解有助于开发严重急性呼吸综合征-冠状病毒-2 (SARS-CoV-2)疫苗。SARS-CoV-2的基因序列一经公布,全球就开始围绕不同的疫苗平台技术展开激烈的活动。在这些平台中,病毒载体黑猩猩腺病毒牛津1 (ChAdOx1)-先前研究用于各种适应症,包括用于中东呼吸综合征冠状病毒(MERS-CoV)疫苗,目前适用于ChAdOx1 nCoV-19(新型冠状病毒-19)。因此,本系统综述旨在探讨ChAdOx1平台在SARS-CoV和MERS-CoV(致命的人类冠状病毒)疫苗开发中的潜力。为此目的,通过电子数据库进行了高度敏感的文献检索,检索了1 445篇相关文章,其中8篇文章是根据以前的资格标准选出的。文章的收集表明,先前的方法(参考ChAdox1平台)有助于开发针对lh - cov的疫苗,并且到目前为止,ChAdox1 (nCoV-19和MERS)疫苗是安全的和免疫原性的。然而,必须强调的是,需要进一步的研究来确保疫苗对人类的有效性。
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引用次数: 0
Bacterial Expression of TMTP1-Fused L-Asparaginase for Targeting Leukemia and Metastatic Tumor Cells TMTP1融合L-天冬氨酸酶靶向白血病和转移瘤细胞的细菌表达
Q3 Medicine Pub Date : 2023-07-12 DOI: 10.18502/acta.v61i4.13173
M. Kheirandish, Mohammad Tollabi, Fatemeh Davami, B. Rahmani, Negin Sadat Hashemi Aval, Javad Behroozi, Hossein Zarei Jaliani
L-asparaginase is recognized as a first-line anticancer drug for acute lymphoblastic leukemia (ALL); however, low-substrate specificity and exhibiting glutaminase activity cause various off-target toxicities on normal cells. In the following study, we functionalized wild-type asparaginase with the TMTP1 targeting peptide which specifically targets a variety of hematological and metastatic cancer cells. The peptide sequence was genetically added to the N-terminal end of the asparaginase using the restriction endonuclease-free cloning method. Wild-type and engineered asparaginases were expressed in E. coli and purified by Nickel affinity chromatography column. The in vitro activity of both types of enzymes was evaluated by Nessler’s method. The sequencing results showed that the TMTP1 sequence was added in the correct frame to the asparaginase. Wild-type and TMTP1-fused asparaginases were produced in a soluble state with the specific activity of 172 U/mg and 153 U/mg, respectively. The evidence from this study suggests that TMTP1-fused asparaginase could preserve its solubility and activity compared to the wild-type species and can be proposed for future research in anticancer therapies.  
L-天冬酰胺酶被认为是治疗急性淋巴细胞白血病(ALL)的一线抗癌药物;然而,低底物特异性和表现出谷氨酰胺酶活性会对正常细胞产生各种脱靶毒性。在接下来的研究中,我们用TMTP1靶向肽功能化了野生型天冬酰胺酶,该肽特异性靶向多种血液学和转移性癌症细胞。使用无限制性内切酶克隆方法将肽序列基因添加到天冬酰胺酶的N-末端。野生型和工程天冬酰胺酶在大肠杆菌中表达,并通过镍亲和层析柱纯化。两种酶的体外活性均采用奈斯勒法进行评价。测序结果表明TMTP1序列被添加到天冬酰胺酶的正确框中。野生型和TMTP1融合的天冬酰胺酶以可溶性状态产生,比活性分别为172U/mg和153U/mg。这项研究的证据表明,与野生型物种相比,TMTP1融合的天冬酰胺酶可以保持其溶解度和活性,并可用于未来的抗癌治疗研究。
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引用次数: 0
Seminal Histone Deacetylase, Fructose and Serum Reproductive Hormones as Diagnostic Marker in Sub-Groups of Infertile Males 精液组蛋白脱乙酰酶、果糖和血清生殖激素作为不育男性亚群的诊断标志
Q3 Medicine Pub Date : 2023-07-12 DOI: 10.18502/acta.v61i4.13170
W. Olooto, Hammed A Adenusi, Joseph O Soola, Monisola A Ayodele, Frank E Agidigbi
Accurate diagnosis of the cause of infertility assists in the choice of treatment modalities and amelioration of the associated psychosocial problems. The research was carried out using 75 infertile males and 75 males with proven fertility as controls. The anthropometrics (weight, height) were measured and body mass index (BMI) computed. Venous blood was collected from each participant, allowed to clot, and centrifuged to obtain the serum which was analysed for testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations. Semen was collected by masturbation and analysed for sperm quality, seminal fructose concentration, and histone deacetylase (HDAC) activities. A non-significant difference (P>0.05) in weight, height, and BMI; a significant increase (P<0.05) in ejaculated volume, serum LH, FSH, seminal fructose concentrations and HDAC activities; and a decrease in sperm count, sperm motility, serum testosterone concentration was observed among subgroups of infertile men. A direct and significant correlation exists between seminal HDAC activities and fructose concentration. Also, an inverse non-significant correlation exists between HDAC activities and spermatozoa motility. Base on the result obtained from this study, it can be concluded that measuring seminal fructose and HDAC activities in addition to routine biochemical and biophysical parameters will assist in diagnostic work up in subgroups of male infertility.
准确诊断不孕原因有助于选择治疗方式和改善相关的心理社会问题。这项研究使用了75名不育男性和75名已证实生育能力的男性作为对照。测量人体测量(体重、身高)并计算体重指数(BMI)。从每个参与者身上采集静脉血,使其凝结,并离心获得血清,对血清中的睾酮、卵泡刺激素(FSH)和黄体生成素(LH)浓度进行分析。通过手淫收集精液,并分析精子质量、精液果糖浓度和组蛋白脱乙酰酶(HDAC)活性。体重、身高和BMI差异无统计学意义(P>0.05);射精量、血清LH、FSH、精果糖浓度和HDAC活性显著升高(P<0.05);不育男性亚组的精子数量、精子活力、血清睾酮浓度下降。精液HDAC活性与果糖浓度之间存在直接且显著的相关性。此外,HDAC活性与精子活力之间存在着不显著的反向相关性。根据这项研究的结果,可以得出结论,除了常规生化和生物物理参数外,测量精液果糖和HDAC活性将有助于男性不育亚组的诊断工作。
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引用次数: 0
Molecular Diagnosis Challenge in COVID-19 Pneumonia Phase 新冠肺炎肺炎阶段的分子诊断挑战
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12744
Baqer Moradi, Javad Sedaghati, A. Abedi
The Article Abstract is not available.
文章摘要不可用。
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引用次数: 0
Systemic Sarcoidosis With a Pseudo-Tumoral Phenotype 具有伪肿瘤表型的系统性结节病
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12743
D. Chebbi, R. B. Salah, F. Frikha, H. Fourati, M. Ghribi, Z. Mnif, Z. Bahloul
Sarcoidosis is a systemic disease histologically characterized by the presence of non-caseating granulomas. Granulomas can affect all structures of the body, giving heterogeneous manifestations and making the diagnosis of this disease a real challenge. We report the case of a 72-year-old woman who presented with two rare manifestations of sarcoidosis: an orbital and a pulmonary pseudotumor. The orbital tumor revealed the disease. Clinically, the patient had palpebral swelling. Orbital MRI showed an orbital pseudotumor hypointense on T1, and hyperintense on T2, heterogeneous and enhanced after gadolinium injection. The thoracic localization was asymptomatic, revealed by the chest Computed Tomography (CT) scan. Histological evidence of granuloma was obtained at both locations. The level of angiotensin-converting enzyme was high. All the other systemic granulomatous diseases were eliminated. We started a systemic corticotherapy with good clinical results.
结节病是一种组织学上以非干酪化肉芽肿为特征的全身性疾病。肉芽肿可以影响身体的所有结构,表现各异,使该病的诊断成为一个真正的挑战。我们报告的情况下,72岁的妇女谁提出了两个罕见的结节病的表现:眼眶和肺假瘤。眼眶肿瘤显示了这种疾病。临床表现为眼睑肿胀。眼眶MRI显示眼眶假瘤T1低信号,T2高信号,钆注射后不均匀强化。胸部计算机断层扫描(CT)显示,胸部定位无症状。两个部位均有肉芽肿的组织学证据。血管紧张素转换酶水平高。所有其他系统性肉芽肿疾病均被消除。我们开始了全身皮质治疗,临床效果良好。
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引用次数: 0
Association of the Thyroid Nodules' Sonographic Features With Fine Needle Aspiration (FNA) Cytology Results 甲状腺结节超声特征与细针穿刺细胞学结果的关系
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12738
Hossein Ghanaati, Alireza Arefzadeh, Hamidreza Hosseinpour, Mahsa Alborzi Avanaki, Alireza Abrishami, Amir Hossein Jalali
Thyroid nodules are a common finding in clinical practice. Although ultrasonography is an accepted method for evaluating these nodules, Fine Needle Aspiration (FNA) is the procedure of choice for assessing the risk of malignancy. This study aims to determine the association between sonographic features of thyroid nodules based on Thyroid Imaging Reporting and Data System classification and the cytology results. In this prospective cohort study, 147 patients from Tehran Medical Imaging Center who had thyroid nodules underwent ultrasonography-guided FNA, and their sonographic features were recorded. The pathologic findings were also obtained according to the Bethesda system. Finally, the association between sonographic features and cytological results was analyzed. Eighteen (12.3%) nodules were malignant, and 129 nodules (87.7%) were benign. The association of TIRADS categories with the risk of malignancy is as follows: TIRADS 1 (n=0, 0%), TIRADS 2 (n=10, 16.9%), TIRADS 3 (n=6, 10.5%), TIRADS 4 (n=2, 16.7%), and TIRADS 5 (n=0, 0%). The bloody lamellae of thyroid nodules were significantly correlated with the risk of malignancy (P<0.05). However, there was no statistically significant association between the risk of malignancy and gender (P=0.47), calcification (P=0.9), firmness (P=0.19), halo sign (P=0.95), location of nodules (P=0.35), and nodules' echogenicity (P=0.058). Although there are trusted classifications such as TIRADS for categorizing thyroid nodules, there is still uncertainty in utilizing them, especially in the management of nodules classified as TIRADS 2, in which various sonographic features are shared between benign and malignant nodules.
甲状腺结节是临床实践中常见的发现。虽然超声检查是一种公认的评估这些结节的方法,但细针穿刺(FNA)是评估恶性肿瘤风险的首选方法。本研究旨在探讨基于甲状腺影像学报告和数据系统分类的甲状腺结节超声特征与细胞学结果之间的关系。在这项前瞻性队列研究中,来自德黑兰医学影像中心的147例甲状腺结节患者接受了超声引导下的FNA检查,并记录了他们的超声特征。并按Bethesda系统进行病理检查。最后,分析了超声特征与细胞学结果的关系。恶性结节18例(12.3%),良性结节129例(87.7%)。TIRADS分类与恶性肿瘤风险的关系如下:TIRADS 1 (n= 0,0%)、TIRADS 2 (n= 10,16.9%)、TIRADS 3 (n= 6,10.5%)、TIRADS 4 (n= 2,16.7%)和TIRADS 5 (n= 0,0%)。甲状腺结节血片状与恶性肿瘤发生风险显著相关(P<0.05)。然而,恶性风险与性别(P=0.47)、钙化(P=0.9)、坚固度(P=0.19)、晕征(P=0.95)、结节位置(P=0.35)、结节回声增强(P=0.058)之间无统计学意义。虽然有可靠的分类,如TIRADS对甲状腺结节进行分类,但使用它们仍然存在不确定性,特别是在TIRADS 2分类的结节的管理中,其中良性和恶性结节的各种超声特征是相同的。
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引用次数: 0
Immune Checkpoint Inhibition for Pancreatic Cancer 免疫检查点抑制胰腺癌
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12735
S. A. Nejadghaderi, S. Razi, Mahsa Keshavarz-Fathi, N. Rezaei
Pancreatic cancer is one of the ten most lethal cancers with a mortality rate of 5.7 per 100,000 individuals worldwide. According to the disease stage, its 5-year survival rate is between 3% and 34%. Treatment options for pancreatic cancer are surgery, chemotherapy, radiotherapy, and immunotherapy. Immune checkpoint inhibitor therapy is a kind of immunotherapy. Immune checkpoints on T cells like cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) suppress the immune system by attaching to their ligands on normal and/or tumor cells. This mechanism protects the body against immune system hyperactivity, especially in autoimmune diseases, but tumor cells can escape from immune responses by expressing these ligands to maintain in the body and to be safe against the immune system. Immune checkpoint inhibitors are immunotherapeutic drugs that bind to proteins in cancer cells to prevent them from suppressing the immune system. Immune checkpoint inhibitors may lead to some adverse effects like vitiligo, thyroiditis, adrenal insufficiency, and other ophthalmologic, hematologic, and respiratory problems. However, it has been shown that the combination of these therapies with each other or other therapeutic approaches could increase the safety and efficacy of this developing method. Here, we will review some trials that have been done or are ongoing about the advances and the effects of immune checkpoint inhibitors on patients with pancreatic cancer.
癌症是十大最致命的癌症之一,死亡率为全球每100000人5.7人。根据疾病分期,其5年生存率在3%至34%之间。胰腺癌症的治疗选择包括手术、化疗、放疗和免疫疗法。免疫检查点抑制剂治疗是一种免疫疗法。T细胞上的免疫检查点,如细胞毒性T淋巴细胞相关蛋白-4(CTLA-4)和程序性细胞死亡蛋白-1(PD-1),通过附着在正常和/或肿瘤细胞上的配体来抑制免疫系统。这种机制可以保护身体免受免疫系统过度活跃的影响,尤其是在自身免疫性疾病中,但肿瘤细胞可以通过表达这些配体来逃避免疫反应,从而在体内维持并安全对抗免疫系统。免疫检查点抑制剂是一种免疫治疗药物,与癌症细胞中的蛋白质结合,以防止它们抑制免疫系统。免疫检查点抑制剂可能会导致一些不良反应,如白癜风、甲状腺炎、肾上腺功能不全以及其他眼科、血液学和呼吸系统问题。然而,已经表明,这些疗法相互结合或其他治疗方法可以提高这种开发方法的安全性和有效性。在这里,我们将回顾一些已经完成或正在进行的关于免疫检查点抑制剂对癌症患者的进展和影响的试验。
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引用次数: 0
Analyses of Kidney Biomarkers in Patients With SARS-CoV-2 (COVID-19) SARS-CoV-2 (COVID-19)患者肾脏生物标志物分析
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12739
Mohammad Bakhshivand, Farid Ghorbaninezhad, Tohid Kazemi, Parisa Lotfinejad, V. Khaze, Jalil Masoudfar, Somayyeh Mirzaei, Zahra Asadzadeh, Khalil Hajiasgharzadeh, A. Derakhshani, Nazila Alizadeh, B. Baradaran
The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4 %) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4 %) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.
新型冠状病毒最早在中国报告,并在全球范围内引发了广泛的肺炎疫情,并在中国和许多其他国家迅速传播。急性肾损伤是新冠肺炎的重要并发症之一,已在一些病例中得到证实。探索新冠肺炎患者肾功能生物标志物的诊断特征可能有助于更好的患者管理。我们收集了206名确诊患有新冠肺炎疾病的患者的实验室数据,并评估了他们的肾脏生物标志物、血尿素氮(BUN)和肌酸酐。患者的年龄范围几乎为62岁。死亡患者和康复患者的平均年龄分别为71岁和54岁。患者的平均LDH值为755 U/L,肌酸激酶(CPK)为267 U/L。2019冠状病毒病患者的平均BUN为59.1 U/L,肌酐为1.5 U/L。在所有193名患者中,实验室结果显示163名(85.4%)患者BUN水平升高。根据总患者的肌酐水平,实验室结果显示49名(25.4%)患者的肌酐值升高。死亡患者的BUN平均值为85 mg/dL,而康复患者为40.5 mg/dL(P<0.0001)。此外,死亡患者的平均肌酸酐水平为1.86mg/dL,康复患者为1.24mg/dL(P=0.0004)。新冠肺炎疾病后的炎症会导致肾损伤,尿素和肌酸酐水平升高,这可能会增加这些患者的死亡风险。
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引用次数: 0
Naturally Occurring Mutations in HIV-1 Protease Gene Among People Living With HIV HIV-1蛋白酶基因在HIV感染者中自然发生的突变
Q3 Medicine Pub Date : 2023-05-22 DOI: 10.18502/acta.v61i3.12736
Zahra Hasanshahi, Ava Hashempour, Javad Moayedi, Z. Musavi, Behzad Rezaei, B. Dehghani, F. Ghasabi
The emergence of resistance to antiretroviral drugs is the main problem in their long-term efficacy and by considering the wide use of protease inhibitors (PIs), monitoring drug resistance mutations is necessary. Therefore, this study aimed to investigate the PIs drug resistance mutations in Iranian patients as well as subtyping using bioinformatics analysis. Fifteen Iranian patients living with Human Immunodeficiency Virus (HIV) (PLWH) were examined. RNA was used to amplify and sequence the HIV protease gene; also, HIV viral load was determined for all samples. The sequencing results were analyzed by several strong bioinformatics tools to determine the drug-resistance mutations and HIV subtypes. Some polymorphisms in the protease gene were recognized; however, there was no significant rate of major or minor drug resistance mutations in our studied patients. Subtyping analysis revealed the new subtype (D) and the previously reported ones, A and CRF-AD 35, in patients. This study confirmed that the resistance mutations and genetic polymorphisms of the protease region are rare in Iranian-infected patients that can be concluded that prescribing protease inhibitor class in HIV-infected patients is promising in controlling HIV in Iran. In addition, conducting periodic studies to determine the new mutations and the rate of drug resistance to PIs in Iranian individuals highlights the importance of WHO guidelines that recommends monitoring of genotypic-resistance testing and investigation of mutations in HIV-related genes.
抗逆转录病毒药物耐药性的出现是其长期疗效的主要问题,通过考虑蛋白酶抑制剂(PI)的广泛使用,监测耐药性突变是必要的。因此,本研究旨在研究伊朗患者的PIs耐药性突变,并利用生物信息学分析进行分型。对15名伊朗人免疫缺陷病毒(HIV)患者进行了检查。RNA用于扩增和测序HIV蛋白酶基因;此外,还测定了所有样本的HIV病毒载量。测序结果通过几个强大的生物信息学工具进行分析,以确定耐药性突变和HIV亚型。蛋白酶基因中的一些多态性被识别;然而,在我们研究的患者中,没有显著的主要或次要耐药性突变率。亚型分析揭示了患者中新的亚型(D)和先前报道的亚型A和CRF-AD 35。这项研究证实,蛋白酶区域的耐药性突变和遗传多态性在伊朗感染患者中很少见,可以得出结论,在伊朗,为HIV感染患者开具蛋白酶抑制剂类处方有助于控制HIV。此外,定期进行研究以确定伊朗个体的新突变和对PIs的耐药性,突出了世界卫生组织指南的重要性,该指南建议监测基因型耐药性检测和调查艾滋病毒相关基因的突变。
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