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Guo-Shuai Lin,* Mao-Mao Zhao,* Xiao-Qing Li, Hong-Xia Yu Department of Infectious Disease, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, People’s Republic of China*The authors contributed equally to this workCorrespondence: Hong-Xia Yu, Department of Infectious Disease, Yantai Yuhuangding Hospital, Yantai, Shandong, 264000, People’s Republic of China, Tel +86 15053573266, Email yuhongxiag6d@163.comBackground: Infective endocarditis (IE) can be caused by a variety of pathogens. Endocarditis due to the Coxiella burnetii (C. burnetii) infection is common in patients with negative blood culture results and usually occurs in patients with previous valvular heart disease, impaired immune function, and during pregnancy. The diagnosis is difficult based on the conventional diagnostic method, and serious adverse outcomes may occur in the case of delayed diagnosis.Case Report: In the present study, a case of a 43-year-old male patient with previous valvular heart disease was reported. The patient was admitted with a diagnosis of IE, but the etiology was unclear. Accurate diagnosis and treatment were achieved by combining metagenomic next-generation sequencing (mNGS) with Q fever serological antibody assay.Conclusion: Metagenomic next-generation sequencing has been increasingly applied in clinical practice in recent years to detect the DNA or RNA in samples, and this could play a decisive role in the etiological diagnosis of some infectious diseases.Keywords: Q fever, endocarditis, diagnosis, metagenomic next-generation sequencing

Introduction: Community-acquired pneumonia (CAP) is a global disease responsible for a large number of deaths, with significant economic impact. As diagnostic tools have increased in sensitivity, understanding of the etiology of CAP has begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP. Macrolides and related antibiotics are first-line treatments for M. pneumoniae. Macrolide resistance has been spreading for 15 years and now occurs in worldwide. We undertook the first study on macrolide resistance of M. pneumoniae in Yantai. This may be helpful to determine the appropriate therapy for CAP in this population. Objective: To investigate the rate and mechanism of macrolide resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult CAP patients. Samples were assayed by polymerase chain reaction (PCR) and cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by sequencing. Twenty-seven strains of M. pneumoniae were isolated and the activities of nine antibiotics against M. pneumoniae were tested in vitro. Results: Out of 128 samples tested, 27 were positive for M. pneumoniae. Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of macrolides resistance was A2063G point mutation in the sequence directly binding to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for the fluoroquinolone group was 4.7 ±2.9 d, which was significantly shorter than 8.2 ±4.1 d for the azithromycin group. Conclusions: Macrolides are not the first-line treatment for M. pneumoniae respiratory tract infections in Yantai. Resumen Introducción: Neumonía adquirida por en la comunidad (NAC) es una enfermedad responsable por un gran número de muertes y un impacto económico importante. Debido a que el diagnostico incrementó la sensibilidad, se cambió la etiología de la NAC. Adicionalmente, Mycoplasma pneumoniae es uno de los patógenos que causan la NAC. Los macrólidos y antibióticos relacionados son la primera línea de tratamiento para M. pneumoniae. La resistencia a macrólidos se aumentó en los últimos 15 años y ahora se encuentra distribuido en todo el mundo. Nosotros realizamos el primer estudio de resitencia a M. pneumoniae a los macrólidos en Yantai. Esto podría ser útil para determinar una terapia apropiada para NAC en esta población. Objetivo: Investigar la tasa y el mecanismo para la resitencia a los macrólidos en Yantai. Métodos: Se colectaron muestras faringeas usando un hisopo. Las muestras se analizaron mediante la reacción en cadena de la polimerasa (PCR) y por cultivo para M. pneumoniae. Se uso una PCR anidad para amplificar fragmentos del gen 23S rRNA especifico con las mutaciones para M. pneumoniae. Se analizaron amplicomes por CE-SSCP para determinar la resitencia a los macrólidos. Estos resultados se confirmaron por secuenciación. Se aislaron 27 cepas de M. pneumoniae y se probaron nueve antibióticos in vitro. Resultados: De 128 muestras, 27 fueron positivas para M. pneumoniae. Se determinó una resistencia a macrólidos por Mycoplasma del 100%. Los mecanismos de esta resitencia fue una mutacion punctual A2063G en la secuencia que se une directamente a los macrólidos en el dominio 23S rRNA V in vitro. El tiempo piotolítico medio para el grupo de fluoroquinolonas fue 4.7 ±2.9 d, que fue significativamente más corto que para el grupo de azitromicina: 8.2 ±4.1 d. Conclusiones: Los macrólidos no son la primera linea de tratamiento para las infecciones del tracto respiratorio contra M. pneumoniae respiratory tract infections en Yantai.

Human papillomavirus (HPV) is the most common viral infection of the reproductive tract, which can increase the risk of cervical cancer. Development of HPV-specific vaccines that can be recognized and presented by human leukocyte antigen (HLA) system is considered as an important approach to prevention and treatment of cervical cancer. In this study, a combination of bioinformatics analysis and peptide binding assay was described to identify potential cytotoxic T lymphocyte epitopes from the HPV genome. In the procedure, a structure-based quantitative structure–activity relationship (SB-QSAR) was used to analyze the intermolecular interactions between HLA proteins and peptide epitopes, and the obtained nonbonded descriptors were then correlated linearly and nonlinearly with HLA–peptide affinities by using partial least squares regression and support vector machine, respectively. Several SB-QSAR models were established and evaluated rigorously, from which the best predictor was applied to virtual screening against thousands of nonapeptide segments generated from the HPV-16 genome. With this protocol a number of peptide ligands were inferred to have high affinity for a variety of frequently observed HLA-A alleles, including 0101, 0201, 0202, 0203, 0206 and 0301, from which several promising candidates were selected and tested in vitro to determine their binding strength toward HLA proteins. Consequently, several peptides were identified as potent HLA binders with half-maximal binding BL50 at micromolar level. The molecular mechanism underlying the high-affinity binding of identified peptide ligands to HLA proteins was also investigated in detail.